Inflammatory bowel diseases (IBD) represent a growing public health concern due to increasing incidence worldwide. The current notion on the pathogenesis of IBD is that genetically susceptible individuals develop intolerance to dysregulated gut microflora (dysbiosis) and chronic inflammation develops as a result of environmental triggers. Among the environmental factors associated to IBD, diet plays an important role in modulating the gut microbiome, influencing epigenetic changes and, therefore, could be applied as a therapeutic tool to improve the disease course. Nevertheless, the current dietary recommendations for disease prevention and management are scarce and of weak evidence. This review summarizes the current knowledge on the complex interactions among diet, microbiome and epigenetics in IBD. Whereas over-abundance of calories and some macronutrients increases gut inflammation, several micronutrients have the potential to modulate it. Immunonutrition has emerged as a new concept putting forward the importance of vitamins such as vitamins A, C, E, D, folic acid and beta-carotene and trace elements such as zinc, selenium, manganese and iron. However, when assessed in clinical trials, specific micronutrients exerted a limited benefit. Beyond nutrients, anti-inflammatory dietary patterns as a complex intervention approach have become popular over the recent years. Hence, exclusive enteral nutrition in pediatric Crohn’s disease is the only nutritional intervention currently recommended as a first-line therapy. Other nutritional interventions or specific diets including the Specific Carbohydrate Diet, the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol diet and most recently the Mediterranean diet have shown strong anti-inflammatory properties and provide a promise for improving disease symptoms. Definitely, more work is required to evaluate the role of individual food compounds and complex nutritional interventions with potential to decrease inflammation as means for prevention and management of IBD.

Fragile X syndrome (FXS) is a genetic disorder caused by a mutation in the fragile X messenger ribonucleoprotein 1 (FMR1) gene and known to be a leading cause of inherited intellectual disability globally. It results in a range of intellectual, developmental, and behavioral problems. Fragile X premutation associated conditions (FXPAC), also caused by a smaller CGG expansion (55 to 200 CGG repeats) in the FMR1 gene, is linked to other conditions that increase morbidity and mortality for affected persons. Limited research has been conducted on the burden, characteristics, diagnosis, and management of these conditions in Africa. This comprehensive review provides an overview of the current literature on FXS and FXPAC in Africa, epidemiology, clinical features and challenges faced, such as discrimination against affected persons, limited awareness and research, poor access to resources and genetic services and treatment. It further provides an in-depth analysis of the existing worldwide data for the diagnosis and treatment of these disorders. This review will improve understanding of FXS and FXPAC in Africa by incorporating existing knowledge, identifying research gaps, and potential topics for future research to enhance the well-being of individuals and families affected by FXS and FXPAC in the region.

Tumor-associated macrophages (TAMs) are the major component of the tumor microenvironment (TME), where they sustain tumour progression and anti-tumor immunity. Due to their plasticity, macrophages can exhibit anti- or pro-tumor functions through the expression of different gene sets leading to distinct macrophages phenotypes: M1-like or pro-inflammatory and M2-like or anti-inflammatory. NF-κB transcription factors are central regulators of TAMs in cancers, where they often drive macrophage polarization towards M2-like phenotype. Therefore, the NF-κB pathway is an attractive therapeutic target for cancer immunotherapy in a wide range of human cancers. Hence, targeting NF-κB pathways in the myeloid compartment is a potential clinically strategy to overcome microenvironment-induced immunosuppression and increase anti-tumor immunity. In this review, we discuss the role of NF-κB as key driver of macrophage functions in tumours as well as the principal strategies to overcome tumour immunosuppression by targeting NF-κB pathway.

Plastid-encoded RNA polymerase (PEP) forms a multisubunit complex in operating chloroplasts, where PEP subunits and a sigma factor are tightly associated with 12 additional nuclear-encoded proteins. Mutants with disrupted genes encoding PEP-associated proteins (PAPs) provide unique tools for deciphering mutual relationships among phytohormones. A block of chloroplast biogenesis in Arabidopsis pap mutants specifying highly altered metabolism in white tissues induced dramatic fluctuations in the content of major phytohormones and their metabolic genes, whereas hormone signaling circuits mostly remained functional. Reprogramming of the expression of biosynthetic and metabolic genes contributed to a greatly increased content of salicylic acid (SA) and a concomitant decrease in 1-aminocyclopropane-1-carboxylic acid (ACC) and oxophytodienoic acid (OPDA), precursors of ethylene and jasmonic acid, respectively, in parallel to reduced levels of abscisic acid (ABA). The lack of differences in the free levels of indole-3-acetic acid (IAA) between the pap mutants and wild-type plants was accompanied by fluctuations in the contents of IAA precursors and conjugated forms as well as multilayered changes in the expression of IAA metabolic genes. Along with cytokinin (CK) overproduction, all of these compensatory changes aim to balance plant growth and defense systems to ensure viability under highly modulated conditions.

Background and Objectives: Treatment for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) must deal with immunosuppression as well as infections associated with compromised immune system, such as tuberculosis (TB). Our aim was to overcome the gap in the literature concerning the risk of incidental TB after diagnosis of AAV. Materials and Methods: This retrospective population-based cohort study was based on the data from the National Health Insurance Research Database in Taiwan. We used a novel algorithm to identify patients with newly diagnosed granulomatous polyangiitis (GPA) or microscopic polyangiitis (MPA) between January 1, 2000 and December 31, 2012. The primary outcome was risk of incidental TB. Cox proportional hazard models were used to evaluate the association between AAV and incidental TB. Results: A total of 2,257 patients with AAV and a propensity-score matched cohort of 9,028 patients were studied. Overall, patients with AAV were at a 1.48x higher risk of contracting incidental TB than were patients in the matched cohort (adjusted HR 1.48; 95% confidence interval [CI], 1.02-2.15). Note that the highest risk of contracting incidental TB was in the first two years following a diagnosis of AAV, with a nearly 1-fold increase in risk (adjusted HR, 1.91; 95% CI, 1.01-3.60). Female AAV patients were 3.24x more likely than females without AAV to develop TB (adjusted HR 3.24; 95%CI, 1.85-5.67). Conclusion: Patients with AAV face an elevated risk of contracting incidental TB, particularly within the first two years after AAV diagnosis. The risk of contracting TB is higher among female AAV patients than among females without AAV.

Cellular aging has drawn the attention of researchers, scientists, and biotech businesses for the treatment of a number of medical conditions. Cellular aging is primarily defined by consistent cessation of proliferative development in response to internal and external stressors, including DNA damage, telomere shortening, mitochondrial dysfunction, and regulation of the senescence-associated secretory phenotype (SASP). Disturbances involving these factors may contribute to age-related disease development. Therefore, the current review aims to explore anti-aging factors targeting DNA damage response and SASP regulation and their detailed signaling networks. In addition, it provides an opportunity for researchers to identify not only anti-aging targets, but also anti-aging therapeutic strategies based on identified and non-identified targets.

Background and Objectives: Uveitis, a prevalent eye disorder characterized by inflammatory processes, often leads to cataract formation and significant visual impairment. This study aimed to evaluate preoperative conditions and postoperative outcomes following cataract surgery in uveitis patients. Materials and Methods: A retrospective study was conducted at the University Hospital Center Rebro Zagreb, Croatia, involving uveitis patients who underwent cataract surgery between 2013 and 2022. Eligible patients had uveitic cataracts affecting visual acuity or posterior segment visualization in a "quiet eye" and were disease-inactive for at least three months. Patients with certain preexisting ocular conditions were excluded. Data collected included patient demographics, uveitis type, preoperative therapy, preexisting lesions, and postoperative outcomes such as visual acuity, intraocular pressure, central macular thickness, and complications. Statistical analysis was performed to identify risk factors associated with complications. Results: The study included 105 patients. After cataract surgery, there was a significant improvement in visual acuity at various time points, with 90% of eyes showing improvement. Intraocular pressure decreased over time. Central macular thickness increased at three months post-surgery but remained stable thereafter. Early and late complications were observed in 52.4% and 63.8% of eyes, respectively. The most common complications were posterior capsular opacification, macular edema, and epiretinal membrane. Factors associated with complications varied between early and late stages but included age, age at onset of uveitis, and uveitis type. Conclusion: Cataract surgery in uveitis patients presents challenges but can lead to significant visual improvement. This study highlights the importance of careful patient selection, preoperative and postoperative inflammation management, and precise surgical techniques. Although complications were common, they were manageable, and most patients experienced improved vision, emphasizing the benefits of cataract surgery in this population. However, future investigations should address the study's limitations and further refine perioperative strategies.

Background: Fungi are ubiquitous microorganisms that are easily dispersed through the air. In healthcare environments, indoor air can favor the spread of healthcare-associated fungal infections, compromising mainly immunocompromised hospitalized individuals. Thus, this study aimed to evaluate the indoor air contamination in healthcare environments, investigating mainly the presence of potentially pathogenic yeasts. Methods: Indoor air samples were collected from twelve healthcare environments (hospital and medical clinics). After the growth, isolation, and purification of the yeast colonies, the isolates were identified by polymerase chain reaction using species-specific primers for yeasts of the genus Candida and sequencing of D1/D2 domains of the large ribosomal subunit (LSU rRNA). Results: Fourteen yeast species were identified, including emerging pathogens. Species of clinical importance such as Candida parapsilosis, Candida orthopsilosis, Candida glabrata, Rhodotorula mucilaginosa, and Trichosporon mucoides were present. C. Parapsilosis was the most prevalent species, followed by Rodothorula mucilaginosa. Conclusions: The present study shows that potentially fungal pathogens were present in air samples from healthcare environments, proving the role of indoor air in spreading infections. Thus, monitoring air quality in healthcare environments is a fundamental approach in developing infection control measures, especially those related to invasive fungal infections.

Metabolic-associated fatty liver disease (MAFLD) and diabetic kidney disease (DKD) share various pathophysiological factors, and epidemiological evidence suggests that these two diseases are associated. Albuminuria and the estimated glomerular filtration rate, which are conventional biomarkers of DKD, are reportedly associated with the risk or severity of MAFLD. Recently, novel DKD biomarkers reflecting renal tubular injury have been introduced to complement conventional DKD markers. In this article, we looked at previous studies that showed an association between MAFLD and DKD and also reviewed the significance of DKD biomarkers as predictive risk factors for MAFLD.

Cancer associated cachexia (CAC) is a critical contributor to pancreatic ductal adenocarcinoma (PDAC) mortality. Thus, there is an urgent need for new strategies to mitigate PDAC-associated cachexia; and the exploration of dietary interventions is a critical component. We previously observed that a ketogenic diet (KD) combined with gemcitabine enhances overall survival in the autochthonous LSL-KrasG12D/+; LSL-Trp53 R172H/+; Pdx1-Cre (KPC) mouse model. In this study, we investigated the effect and cellular mechanisms of a KD in combination with gemcitabine on the maintenance of skeletal muscle mass in KPC mice. For this purpose, male and female pancreatic tumor-bearing KPC mice were allocated to a control diet (CD), a KD, a CD + gemcitabine (CG), or a KD + gemcitabine (KG) group. We observed that a KD or a KG mitigated muscle strength decline over time and presented higher gastrocnemius weights compared CD-fed mice. Mechanistically, we observed sex-dependent effects of KG treatment, including the inhibition of autophagy, and increased phosphorylation levels of eIF2α in KG-treated KPC mice when compared to CG-treated mice. Our data suggests that a KG results in preservation of skeletal muscle mass. Additional research is warranted to explore whether this diet-treatment combination can be clinically effective in combating CAC in PDAC patients.

Acinetobacter baumannii (AB) is a bacterium that causes infections, particularly in immunocompromised patients. Treatment is challenging due to biofilm formation by AB strains, which hinders antibiotic effec-tiveness and promotes drug resistance. The aim of our study was to analyze the biofilm-producing capacity of AB isolates from various forms of infections in relation to biofilm-related genes and their drug resistance. We tested one hundred isolates for biofilm formation using the crystal violet microplate method. Drug re-sistance analyses were performed based on EUCAST and CLSI guidelines, and biofilm genes were detected using PCR. All tested strains were found to form biofilms, with 50% being ICU strains and 72% classified as strong biofilm-producers. Among these, 87% were extensively drug-resistant (XDR) and 2% were extra extensively drug-resistant (E-XDR). The most common gene set was bap, bfmS, csuE, and ompA, found in 57% of all isolates. Our research has shown that, regardless of the form of infection, biofilm-forming strains can be expected among AB isolates. The emergence of E-XDR and XDR strains among non-ICU infections highlights the necessity for the rational use of antibiotics to stop or limit the further acquisition of drug re-sistance by A. baumannii.

Introduction: Hemostatic dysfunction during extracorporeal membrane oxygenation (ECMO) due to blood-circuit interaction and the consequences of shear stress by flow rates lead to rapid activation of the coagulation cascade and thrombus formation in the ECMO system and blood vessels. In this study, we aimed to identify the incidence and risk factors for cannula-associated arterial thrombosis (CaAT) post-decannulation. Methods: A retrospective study of patients undergoing arterial cannula removal following ECMO. We evaluated the incidence of CaAT and compared clinical characteristics, pre-ECMO severity, and daily hemostasis parameters in patients with and without CaAT. Multivariate analysis revealed the risk factors for CaAT. Results: Forty-seven patients requiring venoarterial ECMO or hybrid methods were recruited to be screened for thrombosis. The median SOFA score was 11 (8-13). CaAT occurred in 29 patients (61.7%), with thrombosis in the superficial femoral artery accounting for 51.7%. Limb ischemia complications in the group with CaAT was 17.2%. In multivariate analysis, an ECMO flow rate of 100 mL/min was determined to be the independent factor for CaAT with an OR of 0.84 (95% CI, 0.73–0.95, p=0.008). Conclusion: In patients successfully weaned from ECMO, the incidence of CaAT was 61.7%. Our study found that a low-flow rate of ECMO was an independent risk factor for CaAT.

The traditional nomenclature system for classifying Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), based on clinical phenotype, described Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA) and Microscopic Polyangiitis (MPA) as distinct clinical entities. This classification has proved its expedience in clinical trials and every day clinical practice, yet, a substantial overlap in clinical presentation still exists, and often causes difficulties in prompt definition and clinical distinction. Additionally, new insights into the AAV pathogenesis point out that PR3 and MPO-AAV may not represent expressions of the same disease spectrum but rather two distinct disorders, as they display significant differences. Thus, it is supported that a classification based on ANCA serotype (PR3-ANCA, MPO-ANCA or ANCA-negative), could be more accurate and also closer to the nature of the disease, instead of the phenotype-based one. This review aims to elucidate the major differences between PR3 and MPO-AAV, in terms of epidemiology, pathogenesis, histological and clinical manifestations, and response to therapeutic approaches.

Classic Hodgkin lymphoma (cHL) is characterized by a few tumor cells surrounded by a protective, immunosuppressive tumor microenvironment composed of normal cells that are an active part of the disease. Hodgkin and Reed-Sternberg (HRS) cells evade the immune system through a variety of different mechanisms. They are invisible to antitumor effector T cells and natural killer cells and promote T cell exhaustion. Using cytokines and extracellular vesicles, they recruit normal cells, induce their proliferation, and “educate” (i.e., reprogram) them to become immunosuppressive and protumorigenic. Therefore, alternative treatment strategies, targeting not only tumor cells but also the tumor microenvironment, are being developed. Here we summarize current knowledge on the ability of HRS cells to build their microenvironment and to educate normal cells to become protective or immunosuppressive. We also describe therapeutic strategies to counteract formation of the tumor microenvironment and related processes leading to T cell exhaustion and repolarization of immunosuppressive tumor-associated macrophages.

Tumor microenvironment including cancer-associated fibroblasts (CAF) has developed as an important target for understanding tumor progression, clinical prognosis and treatment responses of cancer. Cancer cells appear to transform normal fibroblasts (NF) into CAFs involving direct cell-cell communication and epigenetic regulations. This review summarizes the current understanding on miR involvement in cancer cell – tumor environment/stroma communication, transformation of NFs into CAFs, their involved targets and signaling pathways in these interactions; and clinical relevance of CAF-related miR expression profiles. There is evidence that miRs have very similar roles in activating hepatic (HSC) and pancreatic stellate cells (PSC) as part of precancerous fibrotic diseases. In summary, deregulated miRs affect various intracellular functional complexes, such as transcriptional factors, extracellular matrix, cytoskeleton, EMT/MET regulation, soluble factors, tyrosine kinase and G-protein signaling, apoptosis and cell cycle & differentiation, but also formation and composition of the extracellular microenvironment. These processes result in the clinical appearance of desmoplasia involving CAFs and fibrosis characterized by deregulated stellate cells. In addition, modulated release of soluble factors can act as (auto)activating feedback loop for transition of NFs into their pathological counterparts. Furthermore, epigenetic communication between CAFs and cancer cells may confer to cancer specific functional readouts and transition of NF into their pathological counterparts. MiR related epigenetic regulation with many similarities should be considered as key factor in development of cancer and fibrosis specific environment.

Recent advancements in gut microbiome research have highlighted the complex interplay between gut microbiota and various physiological and pathological processes, showing that gut microbiota plays a vital role in human health and disease. Imbalances in the gut microbiota, known as dysbiosis, have been associated with a range of health conditions, including gastrointestinal disorders, metabolic diseases, etc. In response to these findings, probiotics, prebiotics, synbiotics, and postbiotics have emerged as a promising therapeutic strategy to modulate gut microbiota composition and functionality. This review paper explores the latest research on how gut microbiota impacts host physiology, immune responses, and overall well-being. Furthermore, the paper delves into the therapeutic potential of probiotics, postbiotics, prebiotics, and synbiotics in therapeutic applications and curing various diseases. The paper also addresses the challenges and opportunities in the field, highlighting the need for personalized approaches to probiotic therapy and the importance of considering factors such as strain specificity, dosing, and safety.Overall, this review aims to provide a comprehensive overview of the evolving landscape of gut microbiota and probiotics, prebiotics, synbiotics, and postbiotics as novel therapeutic agents. It underscores the potential of harnessing the gut microbiome to improve health, prevent diseases, and complement traditional medical interventions. As research in this field continues to expand, a deeper understanding of the gut microbiota and probiotics, prebiotics, synbiotics, and postbiotics promises new avenues for preventive and therapeutic healthcare strategies.

Emerging evidence suggests that the human vermiform appendix is not a vestigial organ, but rather an immunological organ of biological relevance. It is hypothesised that the appendix acts as a bacterial ‘safe house’ for commensal gut bacteria and facilitates re-inoculation of the colon after disruption through the release of biofilms. To date, no studies have attempted to explore this potential mechanistic function of the appendix. We conducted a pre-post intervention study in adults (n=59) exploring reestablishment of the gut microbiota in those with and without an appendix after colonic disruption via bowel preparation and colonoscopy. Gut microbiota composition was measured one week before and one month after bowel preparation and colonoscopy using 16S rRNA sequencing. We observed between group differences in gut microbiota composition between those with (n=45) and without (n=13) an appendix at baseline. These differences were no longer evident one-month post-procedure, suggesting that this procedure may have ‘reset’ any potential appendix-related differences between groups. Both groups experienced reductions in gut microbiota richness and shifts in beta diversity post-procedure, with greater changes in those without an appendix, and there were five bacterial genera whose re-establishment post-procedure appeared to be moderated by appendicectomy status. This small experimental study provides preliminary evidence of a potential differential reestablishment of the gut microbiota after disruption in those with and without an appendix, warranting further investigation into the potential role of the appendix as a microbial safe house.

This study aimed to determine the impact of a novel formulation of a supplement composed of the natural ingredients: bromelain, quercetin, and Lentinula edodes, on the gut microbiota of healthy adult dogs. Adult healthy female dogs were administered either a placebo (CTR, n = 15) or the supplement (TRT, n=15) over 28 days. Stool samples were collected for 16S rRNA sequencing before supplement administration (T0), at completion of supplement administration (T28), and one week after the end of supplement administration (T35) to characterize changes in the gut microbial communities. QIIME was used to determine both alpha- and beta-diversity and ANCOM-BC was used to identify differences in taxonomic abundances before and after supplementation. We found a significant decrease in overall diversity in CTR group, but no significant differences in overall diversity in the TRT group over time. Furthermore, we found differences in the abundance of several taxa in both CTR and TRT groups but differences in abundance of beneficial bacteria were more pronounced in TRT group. Specifically, we found increases in the abundance of sequences belonging to the genera Bifidobacterium, Lactobacillus, and Pediococcus at T28 in the TRT group with significant increases in Bifidobacterium and Lactobacillus persisting at T35 when compared to T0. Importantly, members of these genera are known to be pro anti-inflammatory and associated with a healthy gut microbiota in dogs. The results of our study show the potential of our supplement to selectively enhance specific beneficial bacterial taxa, offering a targeted approach to modulating the gut microbiome without causing disruptions to the overall equilibrium.

This study addresses the urgent need for sustainable protein sources in aquaculture due to the depletion of marine resources and rising costs. Animal protein sources, particularly poultry by-product meal (PBM) and insect exuviae meal, are investigated as viable alternatives to fishmeal (FM). Research confirms the successful replacement of FM with a combination of PBM and insect exuviae meal (up to 50%) in the diet of European seabass without compromising growth, feed conversion, gut health and liver fat content. In particular, growth performance was robust with both PBM formulations, with the 25% PBM diet showing better results. Histological examinations showed good gut and liver health, contradicting the concerns of previous studies. The study emphasizes the importance of holistic analyzes that go beyond growth parameters and include histomorphological investigations. The results show that PBM in combination with insect/exuviae meal is well tolerated by seabass, which is consistent with literature reports of mitigating negative effects on gut health. A detailed analysis of the microbiota revealed a decrease in the Firmicutes/Proteobacteria ratio due to an increase in potentially pathogenic bacteria. However, the formulation containing insect exuviae partially counteracted this effect by preserving the beneficial Lactobacillus and promoting the synthesis of short-chain fatty acids (SCFA), particularly butyrate. Chitin-rich components from insect exuviae were associated with improved gut health, which was supported by increased production of SCFA, which are known for their anti-inflammatory properties. The study concludes that a combination of PBM and insect/exuviae meal can replace up to 50% of FM in the diet of seabass, supporting sustainable aquaculture practices. Despite some changes in the microbiota, the negative effects are mitigated by the addition of insect exuviae, highlighting their potential as a prebiotic to increase fish productivity and contribute to a circular economy in aquaculture.

Polyphenols and fermentable fibers have shown favorable effects on gut microbiota composition and metabolic function. However, few studies have investigated whether combining multiple fermentable fibers or polyphenols may have additive beneficial effects on gut microbial states. Here, an in vitro fer-mentation model, seeded with human stool combined from 30 healthy volunteers, was supplemented with blends of polyphenols (PP), dietary fibers (FB) or their combination (PPFB) to determine influence on gut bacteria growth dynamics and select metabolite changes. PP and FB blends independently lead to significant increases in the absolute abundance of select beneficial taxa, namely Ruminococcus bromii, Bifidobacterium spp., Lactobacillus spp. and Dorea spp. Total short chain fatty acid concentrations, relative to non-supplemented control (F), increased significantly with PPFB and FB supplementation, but not PP. Indole and ammonia concentrations decreased with FB and PPFB supplementation, but not PP alone while increased antioxidant capacity was only evident with both PP and PPFB. These findings demonstrated that, while the independent blends displayed selective positive impacts on gut states, combination of both blends provided an additive effect. The work outlines the potential of mixed substrate blends to elicit a broader positive influence on gut microbial composition and function to build resiliency toward dysbiosis.

Salmonella Typhimurium infection in pigs is characterized by an intense inflammatory response in early infection which seems to dysregulate host physiology including the gut microbiota. Both, changes in host physiology and microbiome composition, must entail modifications within the gut environment. This study analyzes the gut metabolome in early infected pigs (48 hours after infection) and non-infected controls by untargeted metabolomics (LC–QTOF MS/MS and GC–TOF MS), supported with microbiome data (16S rRNA abundance and prediction functional analyses). The metabolomic profile in Salmonella-infected pigs differed from healthy controls in 39 of these metabolites, including eight amino acids, four bile acids and carboxylic acids, three carnitines and sugar derivates, eleven fatty acids and six other compounds. Changes in amino acids abundance and the observed decrease of proteolytic bacteria such as Lactobacillus or Bacteroides could favor the niche colonization by Desulfovibrionaceae. In addition, the decrease in short chain fatty acids and tricarboxylic acids cycle was correlated to a decrease in beneficial bacteria in infected pigs. Interestingly, we observed an increase of bile acids concentration and compounds such as succinic acid or pantothenic acid, which may boost the inflammatory response. Altogether, the results reveal how S. Typhimurium infection alters the gut microbiome composition and prompts changes in the metabolism with a potential interaction between intestinal metabolism and microbiota abundance.

Background: Partially hydrolyzed guar gum (PHGG) is a water-soluble, prebiotic fiber that is used in foods and supplements. The effects of PHGG and its role in gut health are still being studied. The purpose of this study was to evaluate changes in the gut microbiome composition of healthy individuals in response to low-dose PHGG supplementation compared with a low fiber diet. Methods: A randomized, double-blind, placebo-controlled crossover study was performed on 33 healthy subjects (17 male, 16 female). Each subject completed three 14-day treatment periods with a 2-week washout between each period. Treatments included supplementation with 3 g PHGG, 6 g PHGG, or placebo. During all periods, the participants followed a low fiber diet (<14 g/day). Stools were collected on days 0 and 14 of each period. Gut microbiome profiling was performed using 16S rRNA sequencing. Results: Supplementation of 3 g and 6 g PHGG significantly increased Verrucomicrobia on day 14 when compared to the placebo (p=0.0066 and p= 0.0068, respectively). On the genus level, Akkermansia was significantly increased on day 14 with both the 3 g and 6 g PHGG doses (p=0.0081 and p=0.0083). Faecalibacterium was significantly decreased on day 14 with 3 g PHGG (p=0.0054). Conclusion: Supplementing with low doses of PHGG has the potential to cause shifts in gut microbiome composition. By increasing beneficial microbes, PHGG can improve the microbiome composition of healthy individuals and may play a role in the treatment of inflammatory gastrointestinal diseases.

Recent evidence suggests that the lower gut microbiome of ruminants presents roles in their health and environment, including the development of the mucosal immune system, milk production efficiency and quality and subsequent methane emissions. However, there are proportionately fewer studies on this complex microbial community in cattle and region-focus studies are non- existent. Herein, we present the research protocol of the GUTBIOME CY project pertaining to determine the composition of the lower gut microbiome in dairy cows situated in 37 farms across five districts of the island of Cyprus. Detailed questionnaires on animal husbandry and farming practices will be gathered from each farm. Faecal, milk (individual and bulk) and water samples will also be collected from cows and their offspring. Samples will be analysed using a combination of molecular biology and bioinformatics pipelines to define microbiome profiles and antimicrobial resistance (AMR). Information collected from the questionnaires will be use to test for associations between animal husbandry or farming practices and microbiome components and AMR. Collected samples will establish the first dairy cattle biobank in the country for contributing substantially towards scientific advancements in microbiome research and providing insights to all stakeholders, tailored to the unique agricultural context of Cyprus.

The increasing prevalence of diabetes mellitus (DM) worldwide is a cause for global concern. Recent evidence suggests that the interaction between one’s diet and the gut microbiome are key modifiers of diabetes, highlighting the potential role of microbiome-modulating nutraceuticals. This bibliometric analysis examines literature published between 2012 and 2022 to explore trends in the latest research, with additional discussion on major takeaways and future directions. We selected and analyzed 640 articles from an initial pool of 4,099 from the Web of Science using Microsoft Excel 2016 and VOSviewer software (version 1.6.19). Our exploration covered the most common journals, countries, study designs, experimental subjects, types of DM, organisms and nutraceuticals studied, and the most cited articles. We also evaluated the most cited publications in terms of journals, organizations, and countries, along with the collaborative networks among authors, organizations and countries, and the co-occurrence of author keywords from the selection. It is evident from the increasing number of publications each year that this field has attracted growing attention over the last decade. Nonetheless, continued research is essential to sustain this trend. Our overarching study of diabetes research marks steady progress in understanding the role of—and potentially discovering applications of—microbiome modulation to enhance metabolic pathways and health outcomes. Advancements in this field may lead to potential therapeutic applications for specific diets and nutraceuticals that modulate the gut microbiota in DM.

Serine is widely involved in antioxidant synthesis, immune response, and fat metabolism. However, it remains unclear whether dietary serine supplementation affects fat deposition in the skeletal muscles of pigs. Thus, we explored the effects of dietary serine supplementation on growth performance, meat quality, and composition of gut microbes and their metabolites in growing-finishing pigs. Forty-eight boars weighing approximately 20 kg were fed either a basal diet or a basal diet supplemented with 0.15% serine. The results showed that dietary serine increased the daily weight gain and improved the antioxidant ability of pigs, as indicated by the decreased malondialdehyde content and increased glutathione and superoxide dismutase content. Pigs supplemented with serine had better meat quality, as shown by the lower drip loss and higher IMF content. Furthermore, dietary serine increased the relative abundance of Streptococcus and Lactobacillus and decreased the relative abundance of Clostridium_sensu_stricto_1 and Terrisporobacter. Differential microbial metabolites were mostly enriched in metabolic pathways related to lipid synthesis, such as alpha-linolenic acid metabolism and steroid hormone biosynthesis. Correlation analysis showed that the altered metabolites were closely related to the intestinal microbiota. In conclusion, our results suggested that serine serves as a potential additive for improving meat quality in growing-finishing pigs.

Nutrition is one of the most influential environmental factor in both taxonomical shifts in gut microbiota as well as development of Type 2 Diabetes Mellitus (T2DM). Emerging evidence has shown that the effects of nutrition on both these parameters is not mutually exclusive and that changes in gut microbiota and related metabolites such as short chain fatty acids (SCFA) and branched chain amino acids (BCAA) may influence systemic inflammation and signaling pathways that contribute to pathophysiological processes associated with T2DM. With this background, our review highlights the effects of macronutrients, carbohydrates, proteins and lipids, as well as micronutrients, vitamins, and minerals, on T2DM, specifically through their alterations in gut microbiota and the metabolites they produce. Additionally, we describe the influences of common food groups, which incorporate varying combinations of these macronutrients and micronutrients, on both microbiota and metabolic parameters in the context of diabetes mellitus. Overall, nutrition is one of the first line modifiable therapies in the management of T2DM and better understanding of the mechanisms by which gut microbiota influence its pathophysiology provides opportunities for optimizing dietary interventions.

This study evaluated the influence of methotrexate (MTX) and non-surgical periodontal treatment (NSPT) on the composition of the oral-gut microbiota in patients with rheumatoid arthritis (RA). Assessments were performed at baseline (T0), 6 months after MTX treatment (T1), and 45 days after NSPT (T2). The composition of the oral and gut microbiota was assessed by amplifying the V4 region of the 16S gene from subgingival plaques and stools. The results of the analysis of continuous variables were presented descriptively and non-parametric tests were adopted. Thirty-seven patients (27 with periodontitis) were evaluated at T0; 32 patients (24 with periodontitis) at T1; and 28 patients (17 with periodontitis) at T2. Nine individuals were lost to follow-up. MTX tended to reduce the alpha diversity of the oral-gut microbiota, while NSPT appeared to increase the number of different species of oral microbiota. MTX and NSPT influenced beta diversity in the oral microbiota. The relative abundance of oral microbiota was directly influenced by periodontal status. MTX did not affect the periodontal condition but modified the interactions between clinical parameters and the oral-gut microbiota. MTX and NSPT directly affected the composition and richness of the oral-gut microbiota. However, MTX did not influence periodontal clinical parameters.

This research was aimed to apply probiotics in aquaculture to improve fish health and growth performances of Nile tilapia. Fingerlings with a mean initial body weight of 11.43±1.27 and mean initial body length of 6.2±0.84 were stocked in 12 happas. Fish were fed four times daily with four different diets having 30% crude protein at 5% of their body weight and reared for two months. The four diets were control diet, diets treated with Saccharomyces cervisiae, Lactobacillus fermentum and their combinations at a dosage of (1.5×108CFU/ml). Growth performance and gut pathogenic microbial of fish were investigated. Accordingly results indicated that the highest performance interims of body weight gain (33.43±1.65g), daily growth rate (0.51±0.05g), feed conversion ratio (1.89±0.10), and protein efficiency ratio (1.78±0.09) was achieved in fish fed with L. fermentum whereas, the lowest performance (19.83±2.23, 0.33±0.04, 3.52±0.39, and 0.97±0.11) respectively was achieved in fish fed with control diet. Salmonella, Shigella, E. coli and, Proteus were detected in gut of fish. In conclusion, the present study confirmed that Nile tilapia fed with probiotics Lac-tobacillus fermentum and Saccharomyces cerevisiae based diets improved growth and health of Nile tilapia reared under pond culture condition.

China faces a persistent deficiency in feed protein resources. Enhancing the utilization efficiency of indigenous feed protein resources emerges as a viable strategy to alleviate the current deficit in protein feed supply. Corn gluten meal (CGM), characterized by high proportion of crude protein and glutamine, is predominantly employed in animal feed. Nonetheless, the water-insolubility of CGM protein hampers its protein bioavailability when utilized as feed material. This study aimed to augment protein bioavailability, liberate glutamine peptides from CGM, and produce gluta-mine-enriched CGM fermented feed. We executed a co-fermentation protocol using Bacillus subtilis A5, Lactobacillus 02002, and acid protease to generate the CGM fermented feed. Subsequent in vivo experiment with broilers were conducted to assess the efficacy of the fermented product. Findings revealed that the soluble protein, glutamine, small peptides, and lactic acid contents in the fer-mented feed increased by 69.1%, 700%, 47.6%, and 125.9%, respectively. Incorporating CGM fermented feed into the diet markedly enhanced the growth performance and intestinal health of broilers, positively modulated the cecal microbiota structure, and augmented the population of beneficial bacteria, specifically Lactobacillus. These results furnish both experimental and theoretical foundations for deploying CGM fermented feed as an alternative protein feed resource.

Ischemic stroke (IS) is a group of vascular disease concomitant with high morbidity and mortality. Berberine is a bioactive substance and it has known to improve stroke, but the mechanism is yet to be proven. Mice were fed with BBR for 14 days. Then, mice were made into MCAO/R models. Neurological score, infarct volume, neuronal damage and markers associated with inflammation were detected. We tested the changes of intestinal flora in model mice after BBR administration by 16SrRNA sequencing. Chromatography-mass spectrometry was used to detect butyrate chemically. Tissue immunofluorescence was used to detect the changes of microglia and astroglia in mice brain. Our findings suggest that berberine improves stroke outcomes by modulating gut microbiota. Specifically, after MCAO/R mice were given berberine, beneficial bacteria producing butyric acid increased significantly, and the mice also had significantly higher levels of butyric acid. Administration of butyric acid and an inhibitor of butyric acid synthesis, heptyl-coA, showed that butyric acid improved stroke outcomes in model mice. In addition, butyric acid could inhibit the activation of microglia and astrocytes in the brain of model mice, thereby inhibiting the release of inflammatory cytokines IL-6, IL-1β, TNF-α and improving stroke outcomes. Our results suggest that berberine may improve stroke outcomes by modulating the gut flora to increase the abundance of butyric acid. These findings elucidate the mechanisms by which berberine improves stroke outcomes and provide some basis for clinical treatment.

There is a growing interest in the endocannabinoid system and the gut microbiota. Both areas have been suggested to play a role in endometriosis, however this is yet to be studied comprehensively. The purpose of this narrative review is to identify the gaps in endometriosis research in the context of these two areas. It underscores the limited knowledge regarding the involvement of the endocannabinoid system and gut microbiota in endometriosis. Further research in these areas is essential to unlock the therapeutic potential of cannabis and enhance the understanding of endometriosis pathogenesis.

The microbiome is pivotal in maintaining health and influencing disease by modulating essential inflammatory and immune responses. Hepatocellular carcinoma (HCC), ranking as the third most common cause of cancer-related fatalities globally, is influenced by the gut microbiome through bidirectional interactions between the gut and liver, as evidenced in both mouse models and human studies. Consequently, biomarkers based on gut microbiota represent promising non-invasive tools for the early detection of HCC. There is a growing body of evidence suggesting that the composition of the gut microbiota may play a role in the efficacy of immunotherapy in different types of cancer, thus it could be used as a predictive biomarker. In this review, we will dissect the gut microbiome's role as a potential predictive and diagnostic marker in HCC and evaluate the latest progress in leveraging the gut microbiome as a novel therapeutic avenue for HCC patients, with a special emphasis on immunotherapy.

Maternal milk supports offspring development by providing microbiota, macronutrients, micronutrients, immune factors, and hormones. The hormone prolactin (PRL) is an important component of milk with protective effects against chronic non-communicable diseases (NCDs). Because maternal milk regulates microbiota composition and microbiota protect against NCDs, we aimed to investigate whether PRL regulates gut microbiota in newborn mice. 16SrRNA sequencing of feces and bioinformatics analysis were performed to evaluate gut microbiota in mice null for the PRL receptor (Prlr-KO) at the onset of weaning (postnatal day 21). The normalized colon and cecal weights were higher and lower, respectively, in Prlr-KO mice relative to wild-type mice (Prlr-WT). Relative abundance (Simpson Evenness Index), phylogenetic diversity, and bacterial concentration in gut contents were lower in the absence of the PRL receptor. Eleven bacteria species, out of 470, differed between Prlr-KO and Prlr-WT mice with two bacterial genera (Anaerotruncus and Lachnospiraceae) related to NCD development being the most common in Prlr-KO. Furthermore, a higher metabolism of terpenoids and polyketides was predicted in Prlr-KO mice compared to Prlr-WT mice; these metabolites have antimicrobial properties and are present in microbe-associated pathogenicity. In summary, the absence of the PRL receptor changes intestinal microbiota composition, resulting in lower microbiota abundance and richness, which could contribute to NCD development.

Worldwide, the demand for natural and synthetic sweeteners in the food industry as an alternative to refined sugar is increasing. This prompted more research to estimate its safety and effect on health. The gut microbiome is critical in metabolizing selected sweeteners, which might affect overall health. Recently, more studies evaluated the relationship between sweeteners and the gut microbiome. This review summarizes the current knowledge addressing the role played by the gut microbiome in metabolizing selected sweeteners. It also addresses the influence of the five selected sweeteners or their metabolites on GI cancer-related pathways. Overall, the observed positive effect of sweetener consumption on GI cancer pathways, such as apoptosis and cell cycle arrest, requires further investigation to understand the underlying mechanism. Furthermore, more research is needed to address the main challenges of studying the field, thus advancing it further.

Non-alcoholic fatty liver disease (NAFLD) affects about 20–40% of the adult population in high-income countries and is now a leading indication for liver transplantation and can drive to hepatocellular carcinoma. The link between gut microbiota dysbiosis and NAFLD is now clearly established. Through analyses of the gut microbiota with shotgun metagenomics, we observed that compared to healthy controls, Adlercreutzia equolifaciens is depleted in patients with liver diseases such as NAFLD. Its abundance also decreases as the disease progresses and eventually disappears in the last stages indicating a strong association with disease severity. Moreover, we show that A. equolifaciens possesses anti-inflammatory properties, both in vitro and in vivo in a humanized mouse model of NAFLD. Therefore, our results demonstrate a link between NAFLD and the severity of liver disease and the presence of A. equolifaciens and its anti-inflammatory actions. Counterbalancing dysbiosis with this bacterium may be a promising live biotherapeutic strategy of liver diseases..

The non-therapeutic use of antimicrobials in poultry production contribute to the spread of drug-resistant pathogens in both birds and humans. Antibiotics are known to enhance feed effi-ciency and promote growth and weight gain of poultry. New regulatory requirements and con-sumer preferences have led to a reduced use of antibiotics in poultry production and discover natural alternatives to the antibiotic growth promoters. This interest is not just focused on the di-rect removal or inhibition of the causative microorganisms but also the prevention diseases caused by enteric pathogens using a range of feed additives. A group of promising feed additives is short- and medium-chain fatty acids and their derivatives. MCFAs possess antibacterial, anticoccidial and antiviral effects. Also, it has been proven that these acids act synergistically if they are used together with organic acids, essential oils, or probiotics. These fatty acids also benefit intestinal health integrity and homeostasis in broilers. Other effects have also been documented, including increases in intestinal angiogenesis and gene expression of tight junctions. The aim of this review is to give an overview of SCFA, MCFA as alternatives of antibiotic growth promoters and by sum-marizing the current finding in the literature, to show their possible benefits on production, meat quality and gut health in poultry.

Numerous studies have demonstrated that multiple intrinsic and extrinsic factors shape the structure and composition of gut microbiota in a host. The disorder of gut microbiota may trigger various host diseases. Here, we collected fecal samples from wild-caught Japanese geckos (Gekko japonicus) and captive conspecifics fed with mealworms (mealworm-fed geckos) and fruit flies (fly-fed geckos), aiming to examine dietary and sexual correlates of gut microbiota. We used the 16S rRNA gene sequencing technology to determine the composition of gut microbiota. The dominant phyla with a mean relative abundance higher than 10% were Verrucomicrobiota, Bacteroidota and Firmicutes. Gut microbial community richness was higher in mealworm-fed geckos than in fly-fed and wild geckos, and community diversity was higher in mealworm-fed geckos than in wild geckos. Neither alpha nor beta diversity of gut microbiota differed among wild, mealworm-fed and fly-fed geckos. The beta rather than alpha diversity of gut microbiota was sex-dependent. Based on the relative abundance of gut bacteria and its gene functions, we concluded that gut microbiota contributed more significantly to the host’s metabolic and immune functions. Higher diversity of gut microbiota in mealworm-fed geckos could result from higher chitin contents of insects of the order Coleoptera. This study not only provides basic information about the gut microbiota of G. japonicus, but also shows that gut microbiota correlates with dietary habit and sex in the species.

Disorders associated with substance abuse are a major public health crisis with few treatment options. According to World Health Organization (WHO) ethanol is the most widely used drug in the world, and it represents a risk factor for the advent of disease, disability, and eventually death. Foetal Alcoholic Spectrum Disorders (FASD) is a diagnostic term to describe the range of effects that can occur in an individual whose mother drank alcohol during pregnancy. These effects encompass both physical, mental, behavioural and further lifelong disabilities. Besides, ethanol can harm the gut microbiota. Gut microbiome is firstly acquired from the mother and it is crucial for intestinal homeostasis during hosts’ lifetime. It is responsible for producing metabolites that benefits and protects the host from harm microbial colonization. Knowledge about the interactions between human gut microbes and the developing nervous system is still scarce. Nevertheless, animal models have shown that gut bacteria and microbial metabolites are strongly associated with Central Nervous System (CNS) homeostasis. Endotoxins such as Lipopolysaccharides (LPS) are hypothesized to have a major role in neurodegeneration, however, conclusions must be taken with care due to differences in sensitivity between humans and mice. In this review we focus on the role of gut microbiota on the neurodevelopment of mice when ethanol consumption is one of the major stressors during prenatal period. We detail the range of the endotoxin hypothesis in describing endotoxins’ contribution to neurodegeneration and the influence that kynurenine pathway has on the process.

Growing evidence suggests a possible involvement of the intestinal microbiota in generating new neurons, but a detailed breakdown of the microbiota composition is lacking. In this report, we systematically reviewed preclinical rodent reports addressing the connection between the composition of the intestinal microbiota and neurogenesis and neurogenesis-affecting neurotrophins in the hippocampus. Various changes in bacterial composition from low taxonomic resolution at the phylum level to high taxonomic resolution at the species level were identified. As for neurogenesis, studies predominantly used doublecortin (DCX) as a marker of newly formed neurons or bromodeoxyuridine (BrdU) as a marker of proliferation. Brain-derived neurotrophic factor (BDNF) was the only neurotrophin found researched in relation to the intestinal microbiota. Phylum Actinobacteria, genus Bifidobacterium and genus Lactobacillus found the strongest positive while phylum Firmicutes, phylum Bacteroidetes and family Enterobacteriaceae as well as germ-free status, showed the strongest negative correlation towards neurogenesis or BDNF mRNA expression. Age, short-chain fatty acids (SCFA), obesity and chronic stress were recurring topics in all studies identified. Overall, these findings add to the existing evidence of a connection between microbiota and processes in the brain. To better understand this interaction, further investigation based on analyses of higher taxonomic resolution and clinical studies would be a gain to the matter.

Obesity in pregnancy induces metabolic syndrome, low-grade inflammation, altered endocrine factors, placental function, and the maternal gut microbiome. All these factors impact fetal growth and development, including brain development. The lipid metabolic transporters of the maternal-fetal-placental unit are dysregulated in obesity. Consequently, the transport of essential long-chain PUFAs for fetal brain development is disturbed. The mother’s gut microbiota is vital in maintaining postnatal energy homeostasis and maternal-fetal immune competence. Obesity during pregnancy changes the gut microbiota, affecting fetal brain development. Obesity and a high-fat diet in pregnancy can induce placental and intrauterine inflammation and thus influence the neurodevelopmental outcomes of the offspring. Several epidemiological studies observed an association between maternal obesity and adverse neurodevelopment. This review discusses the effects of maternal obesity and gut microbiota on fetal neurodevelopment outcomes. In addition, the possible mechanisms of the impacts of obesity and gut microbiota on fetal brain development are discussed.

We demonstrated the role of natural probiotics 3L, 3 Lactobacilli, in the establishment of a strong and sustainable beneficial healthy gut flora, after chemotherapy through experimental results through in vivo model. Using rat CTX model (immunosuppression induced by cyclophosphamide), we suggested some new adjuvant to chemotherapy as drugs + lactobacillus treament. Further, we proposed a new probiotic formulation (L. acidophilus + L. casei + L. plantarum) to be explored in the prevention of health condition loss by alteration of the general immune system, in numerous studies that reported the use of probiotics involving Lactobacillus in the post-chemo or post-surgical procedures. Here, in our study, Illumina MiSeq sequencing was used to generate sequencing data from microbial genomic DNA libraries, which is appreciable to check for the effects of 3L on bacteria. Microbiome analysis, phylogenetic and classification reports, community data have supported the experiments and the results where 3L had strong beneficial effects on the microbiome. Further, the influence on specific metabolic pathways are assisted in deriving the conclusion of the study (use of 3L for cancer therapy) to the mode of action, mechanistically by correcting microbiota composition and enhancing specific gut metabolic functions.

The human gut microbiota consists of bacteria, archaea, fungi, and viruses. It is a dynamic ecosystem shaped by several factors, which play an essential role in both healthy and diseased states of humans. A disturbance of the gut microbiota, also termed “dysbiosis,” is associated with increased host susceptibility to a range of diseases. Because of splanchnic ischaemia, exposure to antibiotics, and/or underlying the disease critically ill patients loose 90% of the commensal organisms in their gut within hours after the insult. This is followed by a rapid overgrowth of potentially pathogenic and pro-inflammatory bacteria altering metabolic, immune, and even neurocognitive functions and turning the gut into the driver of systemic inflammation and multiorgan failure. Indeed, restoring healthy microbiota by means of faecal microbiota transplantation (FMT) in the critically ill is an attractive and plausible concept in intensive care. Yet, available data from controlled studies are limited to probiotics and FMT for severe C. difficile infection or severe inflammatory bowel disease. Case series and observational trials generate hypothesis that FMT might be feasible and safe in immunocompromised patients, refractory sepsis, or severe antibiotic-associated diarrhea in ICU. There is a burning need to test these hypotheses in randomized controlled trials powered for determination of patient-centered outcomes.

Antibiotic inefficacy in treating bacterial infections is largely studied in the context of developing resistance mechanisms. However, little attention has been paid to combined diseases mechanisms, interspecies pathogenesis and the resulting impact on antimicrobial treatment. This review will consider the co-infections of Salmonella and Schistosoma mansoni. It summarises the protective mechanisms that the pathophysiology of the two infections confer, which leads to an antibiotic protection phenomenon. This review will elucidate the functional characteristics of the gut microbiota in the context of these co-infections, the pathogenicity of these infections in infected mice, and the efficacy of the antibiotics used in treatment of these co-infections over time. Salmonella-Schistosoma interactions and the mechanism for antibiotic protection are not well established. However, antimicrobial drug inefficacy is an existing phenomenon in these co-infections. The treatment of schistosomiasis to ensure the efficacy of antibiotic therapy for bacterial infections should be considered in co-infected patients.

Understanding the importance of gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat associated with low abundance of Faecalibacterium prausnitzii in humans and further, administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed to target F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD) or low (LFD) fat-diet for 12-weeks in Wistar rats (n=10/group). XOS increased F. prausnitzii growth having only minor impact on the GM composition. When supplemented with HFD, XOS prevented hepatic steatosis. The underlying mechanisms involved enhanced hepatic β-oxidation and mitochondrial respiration. 1H-NMR analysis of caecal metabolites showed that compared to HFD, LFD group had healthier caecal short-chain fatty acid profile and the combination of HFD and XOS was associated with reduced caecal isovalerate and tyrosine, metabolites previously linked to NAFLD. Caecal branched-chain fatty acids associated positively and butyrate negatively with hepatic triglycerides. In conclusion, our study identifies F. prausnitzii as a possible target to treat NAFLD with XOS. The underlying preventive mechanisms involved improved hepatic oxidative metabolism.

Probiotics are increasingly used by consumers and practitioners to reduce gastrointestinal (GI) distress and improve gut function. Here, we sought to determine whether addition of supplemental bacteriophages (PreforPro) could enhance the effects of a common probiotic, Bifidobacterium animalis subsp. lactis (B. lactis) on GI health. We conducted a 4-week, randomized, parallel-arm, double-blind, placebo-controlled trial where primary outcomes included self-assessments of GI health, a daily stool log, and 16s rRNA analysis of gut microbial populations. We observed within group improvements in GI inflammation (p=0.01) and a trending improvement in colon pain (p=0.08) in individuals consuming B. lactis with PreforPro, but not in the group consuming only the probiotic. There was also a larger increase in Lactobacillus and short chain fatty acid-producing microbial taxa detected in stool of participants taking PreforPro with B. lactis compared to the probiotic alone. Overall, these results suggest the addition of PreforPro as a combination therapy may alter gut ecology to extend the GI benefits of consuming B. lactis or other probiotics.

Alzheimer's disease (AD) has been the subject of extensive investigation as to its biological underpinnings. However, this has produced little of therapeutic benefit or indeed provided any accepted biomarkers that could tailor treatment. This chapter reviews data on the main pathophysiologic processes that have been widely shown to be altered in AD, including circadian dysregulation, mitochondrial dysfunction, gut dysbiosis, and immune-glia-platelet activation. It is proposed that alterations in the gut microbiome, including gut dysbiosis and increased gut permeability drive changes in mitochondrial function that are intimately associated with significant variations in sirtuin expression. Both mitochondria-located and nucleus/cytoplasm located sirtuins can act on mitochondrial function in different cells and body systems to co-ordinate the ageing-associated changes that underpin AD. The sirtuins are therefore key aspect to a developmental model of AD that is more 'holistic' in perspective, thereby providing a framework for the detection of earlier biomarkers and more successful treatment for the heterogenous nature of AD pathoetiology.

There is robust evidence that major depression (MDD) is accompanied by a low-grade activation of the immune-inflammatory response system, which is involved in the pathophysiology of this disorder. It is also becoming apparent that glia cells are in reciprocal communication with neurons and orchestrate various neuromodulatory, homeostatic, metabolic, and immune mechanisms and have a crucial role in neuroinflammatory mechanisms in MDD. Those cells mediate the central nervous system (CNS) response to systemic inflammation and psychological stress, but at the same time, they may be an origin of the inflammatory response in the CNS. The sources of activation of the inflammatory response in MDD are immense, however, in recent years, it is becoming increasingly evident that the gastrointestinal tract with gut-associated lymphoid tissue (GALT) and increased intestinal permeability to bacterial LPS and food-derived antigens contribute to activation of low-grade inflammatory response with subsequent psychiatric manifestations. Furthermore, an excessive permeability to gut-derived antigenic material may lead to subsequent autoimmunities which are also known to be comorbid with MDD. In this chapter, we discuss fascinating interactions between the gastrointestinal tract, increased intestinal permeability, intestinal microbiota, and glia-neuron crosstalk, and their roles in the pathogenesis of the inflammatory hypothesis of MDD. To emphasize those crucial intercommunications for the brain functions, we propose the term of microbiota-gut-immune-glia (MGIG) axis.

Both lactic acid and short chain fatty acid (SCFA) play important roles in maintenance of intestinal epithelial structure and function. Trilactic glyceride (TLG) obtains both excellences of lactic acid and SCFA. This study was to investigate the effects of trilactic glyceride on growth performance, blood parameters, liver function, intestinal morphology and intestine function of piglets. Twelve weaned piglets (21±2 d) were randomly allocated to two treatment groups: 1) control group, piglets fed the basal diet; 2) TLG group, piglets fed the basal diet supplemented with 0.5 % TLG. On day 21 of the trial, D-xylose (0.1 g/kg·BW) was orally administrated to all piglets and blood samples were collected 1 h thereafter. Then, all the piglets were sacrificed to examine intestinal mucosal morphology and collect fatty tissue, liver and intestinal mucosa for further analysis. The results showed that: compared with the control group, TLG group decreased blood ALB and GGT on day 10 and 20, TLG group decreased blood TP and increased blood TG on day 20 of the trail (p < 0.05); TLG group decreased blood D-xylose and LDL, increased blood HDL (p < 0.05). These data suggested that supplementing trilactic glyceride had beneficial impacts on promoting nutrients’ metabolism, maintaining intestinal integrity, and alleviating oxidative stress and diarrhoea. Further research of molecular mechanisms showed changing expression levels of related proteins and genes, suggesting that these could be involved in the regulation of the impact. The community composition of the gut microbiota was also found to be altered in several operational taxonomic units within the genus, Prevotella (order Bacteroidales), and the order, Clostridiales.

Biological nitrogen (N) provisioning is a seminal function of the gut microbes in several terrestrial insects, given the unbalanced carbon (C) and N ratios of their diets. Although freshwater insects face comparable dietary N limitations like terrestrial insects, little is known about this function by their gut microbiomes. In this study, we investigated microbial nitrate reduction to ammonium pathways as possible routes of biological N provisioning in two freshwater insects; filter-feeding Hydropsychidae and grazers/collectors Baetidae. After incubation in filtered (microbe-free) artificial stream water (ASW) containing dissolved ¹⁵N-labeled nitrate (treatment) or standard nitrate (control), bulk δ¹⁵N values of treatment samples (Baetidae = 100.62 ± 10.23, mean ± S.E.; Hydropsychidae = 76.82 ± 7.20) were significantly higher than controls (Baetidae = 10.14 ± 0.12 ; Hydropsychidae = 9.03 ± 0.20) in both functional feeding groups (F _{(3, 13)} = 296, P < 0.0001). The treatment δ¹⁵N values are cautiously interpreted as reflecting uptake and incorporation of microbe-derived ¹⁵N-metabolites (¹⁵NH₄ or ¹⁵N-amino acids) into host tissues following nitrate reduction to ammonium pathways in the gut lumen. Microbial nitrate reduction to ammonium activities was assessed via the quantification of dissimilatory (nrfA) and assimilatory (nasA) nitrate reduction to ammonium gene transcripts. There were no significant differences between control and treatment groups within each insect groups. Overall, this study provides a demonstration of the feasibility of applying ¹⁵N-stable isotope analysis for investigating, potential symbiotic functions of freshwater insect gut microbiomes, despite the preliminary nature of the results.

Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities and neutrophil bacterial killing. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to impairment of homeostasis in the inter-tissue metabolism of amino acids. For this reason, glutamine is currently part of clinical nutrition supplementation protocols and/or recommended for immune suppressed individuals. However, in a wide range of catabolic/hypercatabolic situations (e.g. ill/critically ill, post-trauma, sepsis, exhausted athletes) it is currently difficult to determine whether glutamine parenteral or enteral supplementation should be recommended based on the amino acid plasma concentration (glutaminemia). Although the beneficial immune based effects of glutamine supplementation is already established, many questions and evidence for positive in vivo outcomes still remain to be presented. Therefore, this paper provides an integrated review on how glutamine metabolism in key organs is important to cells of the immune system. We also discuss glutamine metabolism, action and important issues related to the effects of glutamine supplementation in catabolic situations.

This research was to investigate beneficial impact and molecular mechanism of B. coagulans on piglets intestine. Twenty-four 21 days old weaned piglets were allotted to three treatments: control group (basal diet), B6 group (basal diet + 2×10⁶ CFU/g B. coagulans), B7 group (basal diet + 2×10⁷ CFU/g B. coagulans). The results showed that compared with control group, B6 and B7 group significantly decreased diarrhea rate and the concent of CHOL, GGT and DAO in plasma; decreased villus height and increase crypt depth in jejunum and ileum; increased the activities of SOD and CAT and decreased the concent of MDA and H₂O₂ in intestine. These data suggested that supplementing B. coagulans had beneficial impacts on promoting nutrients metabolism, maintaining intestinal integrity and alleviating oxidative stress and diarrhea. Futher research of molecular mechanisms showed that, these beneficial impacts were regulated by changing expression levels of related proteins (including HSP70, Caspase-3, Bax, Villin and Occludin), and genes (including RPL4, IFN-α, IFN-β, IFN-γ, MX1, MX2, OAS1, IL-1β, IL-4, CXCL-9, CCL-2, AQP3, SGLT-1, LPL, INSR and b^0,+AT), and altering community composition of gut microbiota (particularly family Clostridiaceae, Enterobacteriaceae, and Veillonellaceae and genus Prevotella, Turicibacter, and Lactobacillus).

This theoretical study presents a novel perspective on the potential anti-inflammatory properties of Bromelain, a natural agent extracted from pineapple stems. The investigation explores the binding capabilities of Bromelain to Apoptosis-associated speck-like containing CARD (ASC), a crucial adapter molecule known for its involvement in inflammatory processes and inflammasome formation. For the first time, these findings suggest that Bromelain exhibits a notable affinity for ASC, indicating its promising role as a natural anti-inflammatory agent. This study sheds light on the molecular interactions that may contribute to Bromelain's therapeutic potential in modulating inflammatory responses.

Background: Human papillomavirus is a common pathogen that infects the skin and mucosal epithelium, is transmitted sexually; causes condylomas or squamous cell carcinomas. Two (16 and 18) of the 150 HPV serotypes are oncogenic types. Studies have been done on the infection by oncogenic human papillomavirus 16/18 and associated factors are found to be very limited in Ethiopia. Objective: This study aimed to assess the prevalence of oncogenic human papillomavirus infection (HPV 16/18) and associated factors among women. Methods: An institutional-based cross-sectional study was conducted among 337 women screened for cervical cancer in two hospitals in East Gojjam Zone from February to April 2021 G.C. Four BSc-qualified nurses who worked in the chosen hospitals collected the data using pretested questionnaire and an HPV test (OncoE6TM Cervical Test) specific to HPV16/18 in cervical swabs. Descriptive analysis was performed to determine the prevalence and a multivariate logistic regression model was used to identify the associated factors of HPV16/18 infection. Finally, statistical significance was declared at P < 0.05.Results: The prevalence of HPV infection was 14.2% (95% CI: 10.7% -18.1%). The mean age of the respondents was 36.7±9.1 years. Women with the age group of 55-65 years (AOR = 7.91, 95% CI: 1.95-32.09), early initiation of sexual intercourse (AOR = 5.36, 95% CI: 1.58-18.13), history of sexually transmitted infection (STI) (AOR = 3.52, 95% CI: 1.27-9.72), human immunodeficiency virus (HIV) positive status (AOR = 6.8, 95% CI: 1.99-23.54), and number of lifetime sexual partners (AOR = 4.37, 95% CI: 1.15-17.3) were important independent factors associated with the presence of oncogenic HPV infection. Conclusion and Recommendation: We found a relatively low prevalence of high-risk HPV infection. Age, early initiation of sexual intercourse at less than 18 years, STI of women, being HIV seropositive, and a number of sexual partners were important factors for high-risk HPV infection. Women aged > 46 years, women with early initiation of sex, a history of STI, being HIV positive, and a history of multiple sexual partners should be encouraged to be screened and vaccinated for HPV infection. Wider-ranging studies are also needed in HPV-infected women in association with the cervical lesion.

Objectives: The term "inflammageing” describes the process of inflammation-induced aging that leads living cells to a state of permanent cell cycle arrest due to chronic antigenic irritation. This in vitro study aimed to shed light on the mechanisms of “inflammageing” on human oral cells. Methods: Primary cultures of human gingival fibroblasts (hGFs) were exposed to variable pro-inflammatory stimuli, including lipopolysaccharide (LPS), Tumor Necrosis Factor-alpha (TNFa), and gingival crevicular fluid (GCF) collected from active periodontal pockets of systemically healthy patients. Inflammageing was studied through two experimental models, employing either late-passage (“aged”) cells (p.10) that were exposed to the pro-inflammatory stimuli or early-passage (“young”) cells (p.1) continuously exposed during a period of several passages (up to p.10) to the above-mentioned stimuli. Cells were evaluated for the expression of beta-galactosidase activity (histochemical staining), senescence-associated genes (qPCR analysis), and biomarkers related to a Senescence Associated Secretory Phenotype (SASP), through proteome profile analysis and bioinformatics. Results: A significant increase (p<0.05) of beta-galactosidase-positive cells was observed after exposure to each pro-inflammatory stimulus. The senescence-associated gene expression included upregulation for CCND1 and downregulation for SUSD6, and STAG1, a profile typical for cellular senescence. Overall, pro-inflammatory priming of late-passage cells caused more pronounced effects in terms of senescence, than long-term exposure of early-passage cells to these stimuli. Proteomic analysis showed induction of SASP, evidenced by upregulation of several pro-inflammatory proteins (IL-6, IL-10, IL-16, IP-10, MCP-1, MCP-2, M-CSF, MIP-1a, MIP-1b, TNFb, sTNF-RI, sTNF-RII, TIMP-2) implicated in cellular aging and immune responses. The least potent impact on the induction of SASP was provoked by LPS and the most pronounced by GCF. Conclusion: This study demonstrates that long-term exposure of hGFs to various pro-inflammatory signals induced or accelerated cellular senescence with the most pronounced impact noted for the late-passage cells. The outcome of this analyses provides insights into oral chronic inflammation, as a potential confounder of age-related diseases.

A retrospective study including 49 women with ovarian clear cell carcinoma between January 2009 and December 2021 at Oxford cancer centre was done. The mean age was 63 years, with 78% post-menopausal. All women underwent cytoreductive surgery with no residual disease (R0) in 39 women. The follow-up time ranged between 12-144 months, with mean of 105.5 months. The 3-year OS was 73.4%, and 3-year PFS was 81.3%, with a mean of 101.7months (95%CI, 84.63-118.93). As expected, women with stage 1 disease had the best outcome. In comparing OS in respect to absence or presence of residual disease, the 3-year OS was 88.6% (95% CI 108.6-141.8), compared to 12.5% (95% CI 4.48-32.11) respectively (P<0.001). In multivariant analysis the variables included were CA 125 (< or >200 IU/ml), Hb (< or >115 g/L), albumin (< or >40 g/L), associated endometriosis, ascites, residual disease, and FIGO staging. FIGO stage was the only independent prognostic indicator of OS with (p<0.05). Surgery to achieve no residual tumour is necessary to improve the prognosis in advanced OCCC. At present, the true challenge is to predict which patients with early-stage disease are at higher risk of recurrence and would most benefit from adjuvant treatments.

Neuroinflammation is a common hallmark in different neurodegenerative conditions that share neuronal dysfunction and a progressive loss of a selectively vulnerable brain cell population. Alongside ageing and genetics, inflammation, oxidative stress, and mitochondrial dysfunction are considered key risk factors. Microglia are considered immune sentinels of the central nervous system capable of initiating an innate and adaptive immune response. Nevertheless, the pathological mechanisms underlying the initiation and spread of inflammation in the brain are still poorly described. Recently, a new mechanism of intercellular signalling mediated by small extracellular vesicles (EVs) has been identified. EVs are nanosized particles (30-150 nm) with a bilipid membrane that carries cell-specific bioactive cargos that participate in physiological or pathological processes. Damage-associated molecular patterns (DAMPs) are cellular components recognized by the immune receptors of microglia, inducing or aggravating neuroinflammation in neurodegenerative disorders. Diverse evidence links mitochondrial dysfunction and inflammation mediated by mitochondrial-DAMPs (mtDAMPs) such as mitochondrial DNA, TFAM and cardiolipin, among others. Mitochondrial-derived vesicles (MDVs) are a subtype of EVs produced after mild damage to mitochondria and, upon fusion with multivesicular bodies (MVBs), are released as EVs to the extracellular space. MDVs are particularly enriched in mtDAMPs which can induce an immune response and the release of pro-inflammatory cytokines. Importantly, growing evidence supports the association between mitochondrial dysfunction, EVs release and inflammation. Here, we describe the role of extracellular vesicles-associated mtDAMPS in physiological conditions and as neuroinflammation activators contributing to neurodegenerative disorders.

In West Africa, research on the hepatitis E virus (HEV) is barely covered despite the recorded outbreaks. The still low level of access to safe water and adequate sanitation is one of the main factors of HEV spread in developing countries. HEV infection induces acute or sub-clinical liver diseases with a mortality rate ranging from 0.5 to 4%. The mortality rate is more alarming (15 to 25%) among pregnant women, especially in the last trimester of pregnancy. Here, we conducted a multicentric socio-demographic and seroepidemiological survey of HEV in Senegal among pregnant women. A total of 1,227 consenting participants attending antenatal clinics responded to our questionnaire. Plasma samples were collected and tested for anti-HEV IgM and IgG by using the WANTAI HEV-IgM and IgG ELISA assay. HEV global seroprevalence was 7.9% with 0.5% and 7.4% for HEV IgM and HEV IgG, respectively. One participant's sample was IgM/IgG positive, while four were declared indeterminate to anti-HEV IgM as per the manufacturer's instructions. From one locality to another, the seroprevalence of HEV antibodies varied from 0 to 1% for HEV IgM and from 1.5 to 10.5% for HEV IgG. The data also showed that seroprevalence varied significantly by marital status (p&lt;0.0001), by the regularity of income (p=0.0043) and by access to sanitation services (p=0.0006). These data could serve as a basis to setup national prevention strategies focused on socio-cultural, environmental and behavioral aspects for a better management of HEV infection in Senegal.

Trace amine-associated receptors (TAARs) are a family of G protein-coupled receptors present in mammals in the brain and in several peripheral organs. Apart from its olfactory role, TAAR5 is expressed in the major limbic brain areas and regulates brain serotonin functions and emotional behaviors. However, most of its functions remain undiscovered. Given the role of serotonin and limbic regions in some aspects of cognition, we used a temporal decision-making task to unveil a possible role of TAAR5 in cognitive processes. We found that TAAR5 knock-out (KO) mice showed a generally better performance due to a reduced number of errors and displayed a greater rate of improvement at the task than WT littermates. However, task-related parameters, such as time accuracy and uncertainty have not changed significantly. Overall, we show that TAAR5 modulates specific domains of cognition, highlighting a new role in brain physiology.

Apomictic plants (reproducing via asexual seeds), unlike sexual individuals, avoid meiosis and egg cell fertilization. Consequently, apomixis is very important for fixing maternal genotypes in the next plant generations. Despite the progress in the study of apomixis, molecular and genetic regulation of the latter remains poorly understood. So far APOLLO (Aspartate Glutamate Aspartate Aspartate histidine exonuclease) is one of the very few described genes associated with apomixis in Boechera species. The centromere-specific histone H3 variant encoded by CENH3 gene is essential for cell division. Mutations in CENH3 disrupt chromosome segregation during mitosis and meiosis since the attachment of spindle microtubules to a mutated form of the CENH3 histone fails. This paper presents in silico characteristic of APOLLO and CENH3 genes, which may affect apomixis. Also, we characterize the structure of CENH3, study expression levels of APOLLO and CENH3 in gynoecium/siliques of the natural diploid apomictic and sexual Boechera species at the stages of before and after fertilization. While CENH3 was a single copy gene in all Boechera species, the APOLLO gene have several polymorphic alleles associated with sexual and apomictic reproduction in the Boechera genera. Expression of the APOLLO apo-allele during meiosis was upregulated in gynoecium of apomict B. divaricarpa downregulating after meiosis until 4th day after pollination (DAP). On the 5th DAP, expression in apomictic siliques increased again. In sexual B. stricta gynoecium and siliques APOLLO apo-allele did not express. Expression of the APOLLO sex-allele during and after meiosis in gynoecium of sexual plants was several times higher than that in apomictic gynoecium. However, after pollination the sex-allele was downregulated in sexual siliques to the level of apomicts and increased sharply on the 5th DAP, while in apomictic siliques it almost did not express. At the meiotic stage, the expression level of CENH3 in the gynoecium of apomicts was two times lower than that of the sexual Boechera, decreasing in both species after meiosis and keep remaining very low in siliques of both species for several days after artificial pollination until the 4th DAP, when the expression level raised in sexual B. stricta siliques exceeding 5 times the level in apomictic B. divaricarpa siliques. We also discuss polymorphism and phylogeny of the APOLLO and CENH3 genes.

The Corona Virus Disease 2019 (COVID-19) outbreak is becoming pandemic with the highest mortality in people with associated comorbidities. These RNA viruses containing four structural proteins usually use spike protein to enter the host cell. It has been demonstrated that Angiotensin Converting Enzyme 2 (ACE2) ,as a part of renin-angiotensin-aldosterone system (RAAS), acts as a host receptor for the virus which is the main target of therapeutic approaches. However, medications acting on RAAS can lead to serious complications especially in people with diabetes and hypertension. To avoid this, other potential treatment modalities should be used in COVID-19 patients with associated comorbidities.

The psychedelic renaissance has reignited interest in the therapeutic potential of psychedelics for mental health and well-being. An emerging area of interest is the potential modulation of psychedelic effects by the gut microbiome - the ecosystem of microorganisms residing in our digestive tract. This review explores the intersection of the gut microbiome and psychedelic therapy, underlining potential implications for personalized medicine and mental health. We delve into the current understanding of the gut-brain axis, its influence on mood, cognition, and behavior, and how the microbiome may affect the metabolism and bioavailability of psychedelic substances. We also discuss the role of microbiome variations in shaping individual responses to psychedelics, along with potential risks and benefits. Moreover, we consider the prospect of microbiome-targeted interventions as a fresh approach to boost or modulate psychedelic therapy's effectiveness. By synthesizing insights from the fields of psychopharmacology, microbiology, and neuroscience, our objective is to advance knowledge about the intricate relationship between the microbiome and psychedelic substances, thereby paving the way for novel strategies to optimize mental health outcomes amid the ongoing psychedelic renaissance.

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged >=65 years in developed countries. Globally, it affects 30-50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many observational studies, such as AREDS-1 and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high fat and high glucose or fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.

Alcoholic liver disease (ALD) is a major cause of chronic liver disease. This term covers a broad spectrum of liver lesions, from simple steatosis to alcoholic hepatitis and cirrhosis. The patho-genesis of ALD is multifactorial and not fully elucidated due to complex mechanisms related to direct ethanol toxicity with subsequent hepatic and systemic inflammation. The accumulation of pro-inflammatory cytokines and the reduction of anti-inflammatory cytokines promote the development and progression of ALD. To date, there are no targeted therapies to counteract disease progression and prevent acute liver failure. Corticosteroids reduce mortality by acting on the hepatic-systemic inflammation. On the other hand, several studies analyzed the effect of the inhibition of pro-inflammatory cytokines and the stimulation of anti-inflammatory cytokines as potential therapeutic targets in ALD. This narrative review aims to clarify the role of the cy-tokines in the pathogenesis and treatment of ALD.

The global increase in obesity has significant health implications, with an increased BMI as a known risk factor for diseases such as type 2 diabetes, cardiovascular diseases, or different cancer types. Long-term effectiveness of diet therapy in addressing morbid obesity is extremely limited with no adequate pharmaceutical agents available as treatment option resulting in bariatric surgery as being the only viable option to achieve and maintain significant long-term weight loss. One important role in the overall human health plays the gut microbiome and its complex composition, which is usually altered and reduced in complexity/diversity in severely obese patients. In this study, the influence of bariatric surgery and the resulting weight-loss on the gut microbiome composition of twelve morbid obese (BMI ≥ 40) female adult central European patients was investigated by comparing the relative abundances of the major microbial phyla Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria prior- and post-surgery. We also aimed to give insight into the major changes of individual prominent and promising future probiotic bacteria characterized by an overall increase in abundance accompanied by a switch of enterotypes. Identifying specific microbial alterations associated with successful weight-loss outcomes may contribute to the development of future therapeutic interventions by supplementation with next-generation probiotics.

Concern for global health security and the environment due to the emergence of antibiotic-resistant bacteria and antibiotic residues in meat and other livestock products has led many countries to restrict the use of antibiotics in animal feed. This experiment was performed to assess the impact of dietary supplementation with a probiotic (Bacillus subtilis) and a postbiotic (Saccharomyces cerevisiae fermentation product) on growth performance, carcass traits, blood haemato-biochemical profile, gut microbiome, gut morphology, and immune response in broilers as an alternative to antimicrobials in poultry production system to minimize the effect on global health security. A total of 324-day-old Ven Cobb 400 broiler chicks were randomly divided into three dietary groups, each containing 12 replicated pens (n = 12), .and each replicate contained nine broiler chickens. The dietary groups consisted of 1) a basal diet without any growth promoting (T1), 2) the basal diet augmented with Bacillus subtilis at 200 g/MT feed (T2), and 3) the basal diet supplemented with Saccharomyces cerevisiae fermentation product at 1.25 kg/MT feed (T3). To calculate body weight gain, all birds and residual feed were weighed on a replicated basis over days 0, 7, 14, 21, 28, 35, and 42; mortality was recorded daily. Each replicate's mortality percentage was calculated and used to adjust BW, ADFI, and FCR calculations at the trial's end. At the end of the trial (42 d), two chickens from each replicate (24 chickens per group) were slaughtered for carcass traits, gut microbiome, and morphology measurements. Blood samples were collected for the haemato-biochemical profile on 35d and antibody titer on 28d and 35d.Feeding with SCFP (T3 group) significantly improved average daily feed intake (ADFI) and average daily gain (ADG) of chickens compared to the T1 (control) and T2 (probiotic) groups from 1 to 14 days of age. FCR was significantly improved (P<0.05) in SCFP-fed birds (T3) relative to the control (T1)over the entire experimental period (1-42 days). Carcass traits and blood haemato-biochemical parameters remained unaffected (P>0.05) by any diets. However, cholesterol levels and concentrations of corticosterone were significantly lower (P<0.05) in SCFP-fed birds (T3) compared to those of the probiotic (T2) and control (T1) groups. Total E. coli, Enterohaemorrhagic E. coli, ESBL-producing Enterobacteriaceae, and Salmonella counts were significantly higher in the T1group compared to T3 and T2 groups (P<0.05) and Salmonella counts were lower in T3 when compared to T2 (P<0.05). However, there was no significant difference in Lactobacillus count among treatment groups. PCR based characterization of ESBL- producing Enterobacteriaceae revealed maximum presence of blaCTX-M-Type (6/15, 40%), followed by blaSHV-Type (5/15, 33.3%) and blaTEM-Type (4/15, 26.6%). No variation in the occurrence pattern of ESBL/beta-lactamase associated genes in the studied ESBL- producing Enterobacteriaceae isolates was observed between the treatment groups. A significant increase in villi height and villi height to crypt depth ratio (VH: CD) (P<0.05) was observed in both T3 and T2 groups. Contrarily, villi widths did not vary across the dietary groups (P>0.05). The control group (T1) displayed a notable deeper in crypts when compared to the T3 and T2 groups (P<0.05). On day 28, the SCFP-fed birds (T3) and those fed the probiotics (T2) exhibited a significant increase (P<0.05) in antibody titers against Newcastle disease virus and Infectious bursal disease virus. Increase in antibody titre against IBDV in birds with the addition of SCFP in the diet was detected for the first time. However, there were no significant differences observed on day 35. The phagocytic activity of neutrophils and lymphocytes in broiler chickens did not show any noticeable variations among the different groups at day 35(P>0.05).It can be concluded that Saccharomyces cerevisiae fermentation product and Bacillus subtilis probiotic could be viable alternatives to antimicrobials in poultry production considering beneficial impacts in broilers fed antibiotic-free diet.

Microbiota-based strategies are a novel auxiliary therapeutic and preventative way of moderating chronic kidney disease. Lactobacillus mixture (Lm) was previously demonstrated to exert a renal-protective function in the CKD mice model. The efficacy of probiotics in pet foods is a relatively new area of study, and thus verifying the potential health benefits is necessary. This study evaluated the efficacy of Lm treats in feline CKD and elucidated the mechanisms underlying host-microbe interactions. CKD cats (2 and 3 stages) were administrated probiotic pet treats daily (10 g) for 8 weeks. The results demonstrated that during the eight weeks of Lm administration, creatinine was reduced or maintained in all cats with CKD. Similarly, gut-derived uremic toxins (GDUT), IS, and TMAO were significantly downregulated in the serum (confidence intervals = 90%). The life quality of the cats also improved. Feline gut microbiome data, KEGG pathway, and renal function indicator analyses revealed the possible mechanisms involved in modulating CKD feline microbial composition. Further regulation of the microbial functions in amino acid metabolism after Lm administration contributed to downregulating deleterious IS, PCS, and TMAO. The current study provides potential adjuvant therapeutic insights into probiotic pet foods or treats for pets with CKD.

Saccharomyces cerevisiae fermentation products (SCFP) can potentially promote gastrointestinal growth and immunity in young livestock. However, reports within the existing literature on the effects of SCFP supplements on calves have been inconsistent; therefore, we perform the following experiments to resolve the inconsistencies. A total of 22 Holstein calves [10 d after birth, BW = 48.93 ± 3.99 kg (mean ± SD)] were assigned randomly into two groups, namely the control group (CON) and SCFP group, each having 11 replicas. The calves in the CON were fed a basal diet, while the SCFP group was fed the basal diet supplemented with 5g/head/d SCFP (NutriTek, Diamond V, Cedar Rapids, IA52404, United States) incorporated into feed. All the calves were regularly fed thrice daily at 08:00, 14:30, and 21:00 and had free access to water. A 5-day adaptation phase was followed by a 45-day experimental period. The results showed that compared to the CON, at the end of the d-45 trial, the body weight was significantly greater in the SCFP group (p < 0.05), and during the 1-45 days, the ADG was higher (p < 0.05). The FCR in the 30-45 days SCFP group was higher (p < 0.05). Furthermore, the apparent digestibility of DM, CP, EE, ADF, Ca, and P were significantly increased in the SCFP group, except for NDF (p < 0.05). The concentration of GH and IGF-1 in serum showed a tremendous increase (p < 0.05) with SCFP supplementation on d 15 and d 45. On d 15, SCFP supplementation significantly increased the serum IgA contents (p < 0.05). Notably, on d 15 and d 45, the serum concentrations of IL-1β, IL-6, and TNF-α reduced (p < 0.001). Moreover, the Actinobacteriota in the SCFP group were significantly lower than those in the CON group (p = 0.034). SCFP significantly increased the abundance of Butyricimonas, Parabacteroides, and Ruminococcus. The differences among sob, Chao1, and PD-tree groups were statistically significant (p < 0.05). In conclusion, these results demonstrate that SCFP supplementation improved ADG, apparent digestibility and serum hormone, enhanced immunity, and regulated gut microbiota, thereby jointly promoting the growth of pre-weaning calves.

Colorectal cancer is the second leading cause of cancer-related mortality worldwide. Numerous pathophysiological mechanisms, such as abnormal cell proliferation, cell differentiation, resistance to apoptosis, invasion of structures adjacent to colorectal tumor cells, and distant metastasis, are involved in colorectal carcinogenesis. These processes are initiated by the complex interaction of a number of genetic and environmental factors, including sedentary lifestyle, obesity, alcohol consumption, smoking or gut microbiota. Despite the significant progress achieved in the diagnostic and therapeutic management of patients with colorectal cancer, there has been recently a noteworthy increase in the incidence of colorectal cancer in individuals below the age of 50 years. Early-onset colorectal cancer has a different frequency of oncogenic mutations, a higher prevalence of mucinous histology, a distinct deoxyribonucleic acid (DNA) methylation profile, a more distal location, and lower survival rates. A significant improvement in the prognosis of these patients can be achieved through the detection and removal of modifiable risk factors, along with the implementation of personalized screening strategies for individuals at high risk for this malignancy. Furthermore, gaining comprehension of the pathophysiological mechanisms by which these risk factors contribute to the process of oncogenesis may facilitate the discovery of novel therapeutic targets.

The most common method for establishing bioequivalence (BE) is to demonstrate similarity of concentration-time profiles in the systemic circulation, as a surrogate to the site of action. However, the similarity, or otherwise, of profiles from two different formulation in the gastrointestinal tract (GIT) may not be associated with same conclusions based on systemic circulation. Here, we have explored the concordance of BE conclusions (or otherwise) for a set of hypothetical formulations based on drug concentration-profiles in various segments of gut vs those in systemic circulation using virtual trials powered by physiologically-based (PBPK) models. Moreover, by changing physiological and biological attributes of the GIT, the impact of Crohn’s Disease on the BE conclusions was explored. The virtual BE (VBE) was applied to an Entocort EC, a pH/time-dependent release formulation of budesonide, as model drug that is targeted at ileum and colon. Substantial “discordance” between the local and systemic outcomes of VBE was observed. Upper GIT segments were much more sensitive to formulation changes than systemic circulation, where the latter led to false conclusions for BE. The ileum and colon showed a lower frequency of discordance with systemic-derived VBE. Nonetheless, a higher f2 value than the default similarity standard (50) was required to achieve local BE. In the case of Crohn’s Disease, a product-specific f2 value might be needed for drugs such as Entocort EC to ensure local BE, knowing the insensitivity of systemic data to show lack of BE. The results, being limited to the single model drug product, Entocort EC, may not provide a a general and conclusive picture. However, for the first time, it demonstrated the potential discordances between the local gut vs systemic BE.

Background: Alkylresorcinols (ARs) are polyphenolic compounds with a wide spectrum of biological activities and potentially implicated in the regulation of host metabolism. The present study is aimed to establish whether ARs can be produced by human gut microbiota and to evaluate alterations in the content of ARs in stool samples of C57BL and db/db and LDLR (-/-) mice in dependence on diet specifications and olivetol (5-n-pentylresorcinol) supplementation in order to estimate a regulatory potential of ARs. Methods: The quantita-tive analysis of ARs levels in mice stool samples was performed using gas chromatography with mass spectrometric detection; fecal microbiota transplantation (FMT) from human donor to germ-free mice was performed to explore whether the intestinal microbiota could produce ARs molecules. Results: A significant increase in the amounts of individual mem-bers of ARs homologues in stool samples was revealed in 14 days after FMT. 5-n-Pentylresorcinol supplementation to a regular-chow diet influences the amounts of sev-eral ARs in stool of C57BL/6 and LDLR (-/-), but not db/db mice. Conclusions: For the first time, we have shown that several ARs can be produced by the intestinal microbiota. Taking into account, that AR concentrations in human serum are correlated with LPS levels and with microbiota diversity indexes in human stool samples, it can be assumed that ARs may serve as quorum-sensing molecules, influencing gut microbiota composition and host me-tabolism as well.

Background: Atherosclerosis (AS), a key pathological contributor of cardiovascular diseases (CVDs), was characterized by formation of atherosclerotic plaque in aortic wall and caused high mortality and morbidity worldwide. Factors contributing to the initiation and progression of AS included vascular endothelial dysfunction, dyslipidemia, inflammation, and oxidative stress. Shexiang Baoxin Pill (SBP) was a traditional Chinese medicine that had been widely applied in clinic and proved to be effective for patients with CVDs. However, the mechanisms underlying its anti-atherosclerotic effects have not been completely elucidated. The study aimed to investigate the protective effects of SBP on AS and its potential mechanisms. Methods: Different dose of SBP was orally administered in apolipoprotein E-deficient (ApoE-/-) mice treated with a high-fat diet (HFD). Histopathological and immunohistochemical analysis, ELISA, untargeted metabolomics analysis, 16S rRNA sequence analysis, and spearman analysis were applied to identify the protective effects and mechanisms of SBP in HFD-induced AS. Results: SBP significantly alleviated HFD-induced atherosclerotic lesion both in aorta and aortic sinus with a reduction in serum levels of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), as well as interleukin-6 (IL-6) and interleukin-1β (IL-1β), and increased high-density lipoprotein cholesterol (HFD-C) level with no significant change of body weight in HFD-induced ApoE-/- mice. Mechanismly, SBP markedly reshaped the gut microbiota composition and associated metabolomic characteristics. 2 differential intestinal floras at phylum level and 8 differential microbes at genus level, 5 metabolic pathways and 9 differential fecal metabolites related to CVDs were figured out. Besides, intensive correlation between 8 differential microbes and 9 fecal metabolites was observed. Conclusions: Our results showed that SBP could improve HFD-triggered serum lipid disorder, systematic inflammation, and contribute to the alleviation of atherosclerotic lesion. The antiatherogenic properties of SBP might partly result from the reshaping of the gut microbiota and fecal metabolic profile.

Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research pro-gresses in the effect of bacterial dysbiosis from a metabolic point of view, particularly on the bio-chemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with an-ti-inflammatory and anti-tumor properties in CRC. Increased daily intake of omega-3 polyun-saturated fatty acids (PUFAs) significantly increases the density of bacteria that are known to produce butyrate. Omega-3 PUFAs have been proposed as a treatment to prevent gut microbiota dysregulation and lower the risk or progression of CRC.

Background: Obesity and diabetes are two metabolic disorders linked by an inflammatory process named insulin resistance (IR). Various research on the role of gut microbiota in developing obesity and its associated disorders has led to the growing interest in probiotic supplementation. Considering the life-threatening complications of diabesity this mini-review explored the effects of probiotic supplementation on IR in obesity-associated diabetes. Method: This review is based on recent articles from 2005-2020, studying the role of probiotic supplementation on glucose and insulin parameters in healthy and diabetic mouse models. Result: Probiotic supplementation altered the gut microbiota composition, increased short-chain fatty acid production, and decreased pro-inflammatory cytokines. Additionally, they decreased intestinal permeability, circulating lipopolysaccharide, and metabolic endotoxemia hence improved insulin sensitivity and reduced obesity. Although multi-strain probiotic supplementation showed greater benefits than single strain interventions, variations in the concentration of probiotics used and the duration of treatment also influenced the results. Conclusion: Probiotic supplementation could manipulate the gut microbiota by reducing intestinal permeability, inflammation and ameliorate IR and obesity-associated diabetes in animal models which requires further long-term clinical studies in humans.

The onset and progression of the salivary and gut microbiota, the transmission and the impact of the salivary microbiota on the development of early fecal microbial communities was herein explored. We characterized the microbiota of 82 faecal and 80 salivary samples, collected from 82 healty newborns at birth, 7, 15, 30, 90 and 180 days of life, by 16S rRNA targeted-metagenomics approach. Correlation heat-maps and co-occurrence networks were used to investigate microbial taxa relationship in saliva, gut and between the two ecosystems. In saliva microbiota, Streptococcus and Staphylococcus appeared as early commensals, dominating this ecosystem through the time, while Fusobacterium, Prevotella, Porphyromonas, Granulicatella and Veillonella were late colonizers. anaerobes as Enterobacteriace, Staphylococcus and Streptococcus, were gut microbiota pioneers, followed by the anaerobic Bifidobacterium, Veillonella, Eggerthella and Bacteroides. Streptococcus, Staphylococcus and Veillonella were shared by gut and saliva ecosystems (core microbiota). Early saliva and gut microbiota seem to evolve independently driven by local adaptation strategies, with the only exception for the oral Streptococcus and Veillonella genera, involved in gut microbiota development as seeding species. A more comprehensive knowledge of how oral microbiota may impact pathophysiological conditions of gut microbiota may open new avenues on the design of postbiotics.

We report on the isolation of the previously uncultured Neocallimastigomycota SK4 lineage by two independent research groups from a wild aoudad sheep rumen sample (Texas, USA) and an alpaca fecal sample (Baden-Württemberg, Germany). Isolates from both locations showed near identical morphological and microscopic features, forming medium-sized white filamentous colonies with a white center of sporangia on agar roll tubes and a heavy biofilm in liquid media. Microscopic analysis revealed monocentric thalli, and spherical polyflagellated zoospores with 7–20 flagella. Zoospore release occurred through an apical pore as well as by sporangial wall rupturing, a duality that is unique amongst described AGF strains. Isolates were capable of growing on a wide range of mono-, oligo-, and polysaccharides substrates. Phylogenetic assessment based on the D1-D2 large rRNA subunit (D1-D2 LSU) and internal transcribed spacer-1 (ITS-1) regions demonstrated high sequence identity (minimum identity of 99.07% and 96.96%, respectively) between all isolates; but low sequence identity (92.4% and 86.7%, respectively) to their closest cultured relatives. D1-D2 LSU phylogenetic trees grouped the isolates as a new monophyletic clade within the Orpinomyces-Neocallimastix-Pecoramyces-Feramyces-Ghazallamyces supragenus group. D1-D2 LSU and ITS-1 sequences from the obtained isolates were either identical, or displayed extremely high sequence similarity to sequences recovered from the same Aoudad sheep sample on which isolation was conducted, as well as several sequences recovered from domestic sheep and few other herbivores. Interestingly, members of the SK4 clade seem to be encountered in animals grazing on summer pasture. We hence propose accommodating these novel isolates in a new genus, Aestipascuomyces (derived from the Latin word for “summer pasture”), and a new species, A. dupliciliberatus. The type strain is Aestipascuomyces dupliciliberatus strain R4.

AMR and drug void have caused huge panic today with few thousand death per year. MDR Typhoid was a serious old disease and caused serious health hazard in humen and animals demanding an update on molecular biology of the status on transferable genetic elements. R-plasmids combined in F’-plasmid and the new MDR conjugative plasmids were shown abundant in Sanmonella ranging 70-440kb with similarities. BlaTEM, blaCTX-M, blaOXA, blaNDM mdr genes were abundant in >50 plasmids analyzed and metal resistant gene clusters are predominant in most large plasmids. Among the acetyltransferase all catA1, aacA1 and aac-1b-cr genes were located. Abundant streptomycin phosphotransferases (StrAB) and rarely colistin resistant Mcr-5/9 phosphoethanolamine–lipid A transferase were detected. Altered isomeric dihydropterote synthases (Sul1/2/3) were present giving sulfamethoxazole resistance and dhfr gene frequently associated giving trimethoprim resistance. Metal resistant gene clusters like SilABC (CusABC), PcoAB, RcnA, terABC, and merABCXT etc were found in many Salmonella enterica plasmids. Toxin genes like HipA and virulence genes like spvABD were located in few plasmids increasing virulence and pathogenesis. Drug efflux genes tetA or tetB and OqxB, floR, CmlA were frequent where as QepA and EamA genes were rarely seen. Thus, Salmonella metal resistant genes combined with antibiotic resistant genes has tried to overcome the both toxic antibiotics and metalions causing Typhoid AMR. Such acquisition spreads salmoniasis in the live stocks (pig, cow, chicken) where toxic soil and water dominate increasing chance of MDR typhoid in human.

Existing evidence suggest that lactoferrin might be beneficial for Alzheimer’s disease. We aimed to determine the effects of lactoferrin intervention on cognitive function from APP/PS1 mice, and possible mechanisms involved in. Both young and middle-aged male APP/PS1 mice were divided into control and lactoferrin group with 16 weeks’ intervention. Lactoferrin intervention had no effects on cognitive function from both young and middle-aged mice, and no key markers involved in Aβ, tau pathology, neuro-inflammation and synaptic plasticity were altered post lactoferrin intervention. In regards to gut microbiota profiles, in the young mice, lactoferrin elevated α diversity index including ACE and Chao 1, and reduced the relative abundance of the genera Bacteroides and Alistipes and elevated Oscillibacter, in addition, Oscillibacter, Anaerotruncus, EF096579_g, EU454405_g, Mollicutes_RF39, EU474361_g, EU774448_g, and EF096976_g were specifically abundant post Lf intervention via LEfSe analysis. In the middle-aged mice, the relative abundance of the phylum Proteobacteria, as well as the genera Oscillospira, Coprococcus and Ruminococcus was significantly reduced post Lf intervention, additionally, S24_7, Bacteroidia, Bacteroidetes and Methylobacterium were specific via LEfSe analysis post lactoferrin intervention. In conclusion, dietary lactoferrin might be beneficial for gut microbiota homeostasis although might have no effects on cognition.

In schizophrenia, a single latent trait underlies psychosis, hostility, excitation, mannerism, negative (PHEMN) symptoms, formal thought disorders (FTD) and psychomotor retardation (PMR). Schizophrenia is accompanied by a breakdown of gut and blood-brain-barrier (BBB) pathways, increased tryptophan catabolite (TRYCAT) levels, bacterial translocation, and lowered natural IgM and paraoxonase (PON)1 activity. The aim of this study was to examine the factor structure of schizophrenia symptom domains and the biomarker correlates of these factors. We recruited 80 patients with schizophrenia and 40 healthy subjects and assessed the IgA/IgM responses to paracellular/transcellular (PARA/TRANS) ratios, IgA responses to TRYCATs, natural IgM to malondialdehyde and Gram-negative bacteria, and PON1 enzymatic activity.Direct Hierarchical Exploratory Factor Analysis showed a bifactorial oblique model with a) a general factor which loaded highly on all symptom domains, named overall severity of schizophrenia (“OSOS”); and b) a single-group factor (SGF) loading on negative symptoms and PMR. We found that 40% of the variance in the OSOS score was explained by IgA/IgM to PARA/TRANS ratio, male sex and education while 36.9% of the variance in SGF score was explained by IgA to PARA/TRANS, IgM to Gram-negative bacteria, female sex (positively associated) and IgM to MDA, and PON1 activity (negatively associated). Schizophrenia phenomenology comprises two biologically-validated dimensions, namely a general OSOS dimension and a single-group negative symptom dimension, which are associated with a breakdown of gut/BBB barriers, increased bacterial translocation and lowered protection against oxidation, inflammation and bacterial infections through lowered PON1 and natural IgM.

Background: Diets based on meat products are not recommended in the case of ulcerative colitis (UC). However, some foods, as those containing high oleic acid and a low omega-6/omega-3 ratio show anti-inflammatory properties. The objective here is to test if some traditional cured meat products, as acorn-fed ham (high levels of oleic acid), may be useful for controlling inflammatory diseases as UC in animal models. Methods: 3 rat cohorts have been used: vegetable rat feed, control ham and acorn-fed ham (a traditional ham where high oleic acid concentration from acorns is storage in the muscle fat). UC was induced with DSS in drinking water ad libitum for one week. Short-chain fatty acids (SCFAs) and 16S rRNA from bacterial populations were analyzed in cecum samples. Colon samples were analyzed for histological parameters (inflammatory cell density, mucosa damages, myeloperoxidase). Results: In the acorn-fed ham cohort, a protective effect was observed with respect to UC disease activity index, inflammatory cells density, colon mucosa alterations, myeloperoxidase levels, blood total antioxidant capacity and lower levels of pro-inflammatory cytokines, in comparison with feed cohort. Both ham diets caused a reduction in Firmicutes and an increase in Actinobacteria, Bacteroidetes and Proteobacteria in comparison with rat feed diet. Also, acorn-fed ham diet induced changes in gut microbiota composition, with pronounced enrichments in anti-inflammatory bacterial genera such as Alistipes, Bacteroides, Blautia, Butyricimonas and Parabacteroides. Conclusions: In the acorn-fed ham cohort, as a result of the dietary intake of oleic acid and low intake of omega-6 fatty acids, a strong preventive effect against UC symptoms was observed, indicating a valuable effect of this traditional Mediterranean cured meat product.

Deficit schizophrenia is characterized by leaky tight and adherens junctions and bacterial translocation. Here we examine whether (deficit) schizophrenia is accompanied by leaky paracellular, transcellular and vascular barriers in the gut and blood brain barriers. We measured IgA responses to occludin, claudin-5, E-cadherin and β-catenin (paracellular pathway, PARA), talin, actin, vinculin and epithelial intermediate filament (transcellular pathway, TRANS) and plasmalemma vesicle-associated protein (PLVAP, vascular pathway) in 78 schizophrenia patients and 40 controls. IgA responses to claudin-5, E-cadherin and β-catenin, the sum of the four PARA proteins and the ratio PARA/TRANS were significantly higher in deficit schizophrenia than in non-deficit schizophrenia and controls. A large part of the variance in PHEMN (psychosis, hostility, excitation, mannerism and negative) symptoms, psychomotor retardation, formal thought disorders, verbal fluency, word list memory, word list recall and executive functions was explained by the PARA/TRANS ratio coupled with plasma IgA responses to Gram-negative bacteria, IgM to malondialdehyde, CCL-11 (eotaxin), IgA levels of the ratio of noxious to more protective tryptophan catabolites (NOX/PRO TRYCATs) and a plasma immune activation index. Moreover, IgA levels to Gram-negative bacteria were significantly associated with IgA to E-cadherin, β-catenin and PLVAP, while IgA levels to claudin-5 were significantly predicted by IgA to E-cadherin, NOX/PRO TRYCAT ratio, Gram-negative bacteria and CCL11. The phenomenology of the deficit syndrome is to a large extent explained by the cumulative effects of lowered natural IgM, breakdown of the paracellular and vascular pathways, increased bacterial translocation, peripheral immune-inflammatory responses and indices of BBB breakdown.

Perturbation in the microbial population/colony index has harmful consequences on human health. Both biological and social factors influence the composition of the gut microbiota and promote gastric diseases. Changes in the gut microbiota manifest in disease progression owing to epigenetic modification in host which influences differentiation and function of immune cells adversely. Uncontrolled use of antibiotics; chemotherapeutic drugs and change in the diet pattern usually contribute to the changes in the colony index of sensitive strains known to release microbial content in the tissue micromillieu. Ligands released from dying microbes induce TLR mimicry on interaction with TLR abnormally which skew hypoxia and sterile inflammation contributing to severity of disease like IBD autoimmunity and cancer. Various modalities/interventions practiced across the globe and future strategies for microbiota based therapeutic approaches with special emphasis on tumor and inflammatory diseases are reviewed here. Therefore the major aim and scope of this manuscript is to both discuss various modalities/interventions across the globe and to design future microbiota based therapeutic approaches for mitigating the burden with special emphasis on tumor and Inflammatory diseases.

Psoriasis is a chronic inflammatory disease characterized by skin lesions. Psoriasis development has been associated both with genetic and environmental factors. Though skin and gut microbiota has been implicated in number of pathologies including atopic dermatitis, inflammatory bowel disease, Crohn’s disease, allergy, obesity, its role has been poorly studied in psoriatic disease, which incorporates both psoriasis and psoriatic arthritis. This literature review summarizes the most recent and major findings on microbiota features in psoriatic disease as well as gives immune system role in the given condition. Despite conflicting findings, psoriasis patients were frequently found to have distinct microbial composition in both skin and guts especially in the major bacterial phyla, Firmicutes, Bacteroidetes, and Akkermansia. Furthermore, bacterial DNA has been found in psoriatic patients both locally and systemically, and altogether suggesting role of bacteria in the chronic disease and future studies in this field.

Muscle mass, strength and physical function are known to decline with age. This is associated with the development of geriatric syndromes including sarcopenia and frailty. These conditions are associated with disability, falls, longer hospital stay, higher readmission rates, institutionalisation, osteoporosis, and death. Moreover, they are associated with reduced quality of life, as well as substantial costs to health services around the world. Dietary protein is essential for skeletal muscle function. Older adults have shown evidence of anabolic resistance, where greater amounts of protein are required to stimulate muscle protein synthesis and therefore require higher daily amounts of dietary protein. Research shows that resistance exercise has the most beneficial effect on preserving skeletal muscle. A synergistic effect has been noted when this is combined with dietary protein, yet studies in this area lack consistency. This is due, in part, to the variation that exists within dietary protein, in terms of dose, quality, source, amino acid composition and timing. Research has targeted participants that are replete in dietary protein with negative results. Inconsistent measures of muscle mass, muscle function, physical activity and diet are used. This review attempts to summarise these issues, as well as introduce the possible role of the gut microbiome and its metabolome in this area.

Gut microbiota play critical roles in development of obese-related metabolic diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes, and insulin resistance, which highlighted the potential of gut microbiota-targeted therapies on these diseases. There are various ways that can manipulate gut microbiota including probiotics, prebiotics, synbiotics, antibiotics and some active components from herbal medicines. In this review, we first reviewed the main roles of gut microbiota in mediating the development of NAFLD, and the advances in gut microbiota-targeted therapies on NAFLD in both the experimental and clinical studies, as well as the conclusions on the prospect of gut microbiota-targeted therapies in the future.

Autism spectrum disorder (ASD) is a neuropsychiatric condition characterized by impaired social interactions and repetitive stereotyped behaviors. Growing evidence highlights an important role of the gut-brain-microbiome axis in the pathogenesis of ASD. Research indicates an abnormal composition of the gut microbiome and the potential involvement of bacterial molecules in neuroinflammation and brain development disruptions. Concurrently, attention is directed towards the role of short-chain fatty acids (SCFAs) and impaired intestinal tightness. This comprehensive review emphasizes the potential impact of maternal gut microbiota changes on the development of autism in children, especially considering maternal immune activation (MIA). The following paper evaluates the impact of the birth route on the colonization of the child with bacteria in the first weeks of life. Furthermore, it explores the role of pro-inflammatory cytokines, such as IL-6 and IL-17a and mother’s obesity as potentially environmental factors of ASD. The purpose of the present analysis is to advance our understanding of ASD pathogenesis, while also searching for the positive implications of the latest therapies, such as probiotics, prebiotics or fecal microbiota transplantation, targeting the gut microbiota and reducing inflammation. This review aims to provide valuable insights that could instruct future studies and treatments for individuals affected by ASD.

Oral squamous cell carcinoma (OSCC) remains an under-studied and significant global cancer killer and dismal survival rates have not changed in decades. A better understanding of the molecular basis of OSCC progression and metastasis is needed to develop new approaches for treating this disease. The supportive network surrounding cancer tumor cells known as the tumor microenvironment (TME) has gained increasing interest lately since it performs essential pro-tumorigenic functions. Cancer-associated fibroblasts (CAFs) are one of the main cell types in the TME and are known to play a key role in influencing the biological behavior of tumors. CAFs present a heterogeneity both in phenotype as well as functions, leading to the suggestion of different CAF subtypes in several cancer forms. The task to subtype CAFs in OSCC has however just begun and there is today no united way of subtyping CAFs in this disease. This review aims to define the features of CAFs and to summarize CAF subtype research in OSCC including aspects as disease prognosis and therapeutic opportunities.

Nowadays, healthcare-associated infections (HAIs) represent a major global public health problem and the burden of these infections is high. In order to reduce the incidence of HAIs and to prevent the spread antibi-otics resistant organisms is mandatory to develop surveillance systems. We undertook a retrospective case-control study of all patients presenting HAIs admitted in Intensive Care Unit (ICU) in order to assess risk factors associated with death among patients with HAIs. Patients admitted to Intensive Care Unit who died were more likely to present an infection with a multidrug resistant bacteria, an infection with Acineto-bacter baumannii, and to suffer from acute myocardial infarction. Among the patients enrolled in the study, a higher probability of death was also observed in association with certain gram-negative pathogens: Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. The longer the patient remains admitted in ICU, the higher the risk of getting an infection that can often become fatal. Acquiring a noso-comial infection also increases the length of hospitalization which will lead to increased financial damage.

This study investigated clinical nurses’ knowledge and visual differentiation ability of the pressure injury classification system (PICS) and incontinence-associated dermatitis (IAD), additionally analyzing possible influencing factors. A convenience sample of 248 nurses took the PICS and IAD knowledge test (KT) and completed the visual differentiation ability test (VDAT), consisting of 21 photographs with clinical information. The overall mean score for correct answers was 12.65±2.90 points in PICS & IAD KT and 11.43±4.57 points in VDAT. Incorrect responses were most common for statements related to stage Ⅱ, Ⅲ, IAD for PICS & IAD KT, and deep tissue pressure injury (DTPI), unstageable, and stage Ⅲ for VDAT. Significant correlations were found between PICS & IAD KT and VDAT (r=.252, p<.001). Factors affecting scores for VDAT were the scores of PICS & IAD KT, debridement experience in nursing patients with PI, and the management frequency of PI and IAD. Results indicate that nurses have an overall understanding of PICS and IAD, but low visual differentiation ability regarding stage Ⅲ, DTPI, and unstageable PI. Continuing education is needed to further improve knowledge and visual differentiation ability for PICS and IAD.

Head and neck squamous cell carcinoma (HNSCC) takes the sixth place among the most common cancers in the world. Abnormal methylation can be one of the reasons for this cancer. The aim of this study was to investigate the DNA promotor methylation status of cancer-associated genes (ATM, APC, CDO1, RB1, TP53, WIF1) in patients with HNSCC. Bisulfite Conversion and Methylation-Sensitive High-Resolution Melting was used for analysis of the DNA methylation level of normal and tumor tissues in 44 patients. There were significant differences in DNA methylation level between patient’s tumor and normal tissues for CDO1 and WIF1 genes in all subjects and subgroups (p<0.05). In T3 subgroup there was significant correlation between CDO1 gene methylation and age in the normal tissue. The same correlation was detected also for the WIF1 gene methylation in tumor tissue samples in the subgroup with T3 and in normal tissue samples in the subgroup with T4 (p<0,05). In all genes no significant differences were found between the subgroups (T2, T3, T4 stage, primary/recurrent lesion, non-keratinizing/keratinizing SCC, age before/ after 50, smokers/non-smokers) of the patients. Thus, changes in the expression of the CDO1 and WIF1 genes can affect mechanisms of the occurrence and development of HNSCC.

The objective of this study is to examine a nonparametric estimate , using the kernel approach, of the conditional distribution function of a scalar response variable that is given a random variable whose values take place in a separable real Hilbert space. The observations will be dependent on one another in a quasi-associated fashion. The pointwise practically perfect consistencies with rates of this estimator are established by us under some broad conditions. The study’s major objective is to investigate the convergence rate of the proposed estimator and its application in the convergence rate and asymptotic normality of the hazard function. The asymptotic normality of the developed estimator is established precisely. Simulation studies were conducted to investigate the behavior of the asymptotic property in the context of finite sample data.

Secretory and membrane proteins are vital for cell activities, including intra- and intercellular communication. Therefore, protein quality control in the endoplasmic reticulum (ER) is an essential and crucial process for eukaryotic cells. Endoplasmic reticulum-associated degradation (ERAD) targets misfolded proteins during the protein maturation process in the ER and leads to their disposal. This process maintains the ER productive function and prevents misfolded protein stress (i.e., ER stress). The ERAD-stimulating factor ER degradation-enhancing α mannosidase-like 1 protein (EDEM1) acts on misfolded proteins to accelerate ERAD, thereby maintaining the productivity of the ER. However, the detail mechanism underlying the function of EDEM1 in ERAD is not completely understood due to lack of established physiological substrate proteins. In this study, we attempted to identify substrate proteins for EDEM1 using siRNA. The matrix component thrombospondin-1 (TSP1) and epidermal growth factor receptor (EGFR) were identified as candidate targets of EDEM1. Their protein maturation status and cellular localization were markedly affected by knockdown of EDEM1. We also showed that EDEM1 physically associates with EGFR and enhances EGFR degradation via ERAD. Our data highlight the physiological role of EDEM1 in maintaining specific target proteins and provide a potential approach to the regulation of expression of clinically important proteins.

Cells respond to a myriad of stressors by senescing, acquiring stable growth arrest, morphologic and metabolic changes, and a senescence-associated-secretory-phenotype (SASP). The heterogeneity of senescent cells (SnCs) and their SASP is vast, yet poorly characterized. SnCs have diverse roles in health and disease and are therapeutically targetable, making characterization of SnCs and harmonization of their nomenclature a priority. The Cellular Senescence Network (SenNet), a NIH Common Fund initiative, will leverage emerging single cell and spatial-omics to identify and map SnCs in numerous organs across the lifespan of humans and mice. A common coordinate framework will integrate the data, using validated, standardized methods, creating public 4-dimensional SnC atlases. Key SenNet deliverables include development of innovative tools/technologies to detect SnCs, biomarker discovery, common annotations to describe SnCs and extensive public data sets. The goal is to comprehensively understand and map SnCs for diagnostic and therapeutic purposes to improve human health.

MicroRNAs (miRNAs) are a class of small non-coding RNAs, which function as regulators of gene expression and contribute in numerous physiological processes. However, little is known referring to miRNAs function in insect chemosensation. In the current study, nine small RNA libraries were constructed and sequenced from the antennae of nymphs, adult males and females of Apolygus lucorum. In total, 399 miRNAs were identified including 275 known and 124 novel miRNAs. Known miRNAs were classified into 71 families, amongst which, 23 families were insect-specific. Expression profile analysis showed that miR-7-5p_1 was the most abundant miRNAs in the antennae of A. lucorum. Altogether, 69708 target genes related to biogenesis, membrane and binding activities were predicted for 399 miRNAs. Particularly, 15 miRNAs were found to target 16 olfactory genes. These miRNAs could be involved in regulation of olfactory-associated genes ex-pression. Comparing the antennae of nymphs, adult males and females, 94 miRNAs were found to be differentially expressed. The expression levels of some differentially expressed miRNAs measured by qPCR were consistent with sequencing results. This study provides a global miRNAs transcriptome in the antennae of A. lucorum and valuable information for further investigation on miRNA-mRNA interactions, especially the functions of miRNAs in regulating chemosensation.

Statistical data on officially registered cases of health care-associated infections (HCAIs) in Ukraine in the period 2009-2019 have been analysed. On average, 5089±756 cases of HCAIs were registered annually. Odessa region of Ukraine is the leading country in the number of reported cases. The majority of HCAIs cases involve surgical and therapeutic invasive interventions and perinatal HCAIs. On average, 78.0±5.8 % of HCAIs cases involved adults. The estimated minimum number of HCAIs in Ukraine was expected to be about 1 million per year. Official statistics on registered cases of HCAIs in Ukraine do not reflect reality, so the system of registration and investigation of HCAIs in Ukraine needs to be reformed.

Relationships between the Farey sequence and the Riemann hypothesis other than the Franel-Landau theorem are discussed. Whether a function similar to Chebyshev’s second function is square-root close to a line having a slope different from 1 is discussed. The nontrivial zeros of the Riemann zeta function can be used to approximate many functions in analytic number theory. For example, it could be said that the nontrival zeta function zeros and the Möbius function generate in essence the same function - the Mertens function. A different approach is to start with a sequence that is analogous to the nontrivial zeros of the zeta function and follow the same procedure with both this sequence and the nontrivial zeros of the zeta function to generate in essence the same function. A procedure for generating such a function is given.

Salmonella infections can lead to intestinal inflammation and metabolic disorders in birds. However, whether ARA metabolism is involved in Salmonella-induced intestinal inflammation remains unclear. This experiment investigated the changes in cecal flora and arachidonic acid (ARA) metabolism in Hainan Wenchang chickens infected with S. Typhimurium using 16s rDNA sequencing and targeted metabolomics. The results showed that the levels of ARA metabolites were increased in the cecum tissue of Wenchang chickens after infection with S. Typhimurium, including prostaglandin E2, prostaglandin F2α, lipoxin A4, ±8(9)-EET, ±11(12)-EET, and ±8,9-DiHETrE. The content of key enzymes for ARA production and metabolism (PLA2 and COX-2) in chicken cecum tissues was increased after S. Typhimurium infection. The relative mRNA levels of inflammatory factors were also increased after infection, including IFN-γ, TGF-β1, IL-4, and IL-6. In HD11 cells, the use of a cyclooxygenase (COX) inhibitor reduced the increased levels of COX-2 and PGF2α induced by S. Typhimurium infection and effectively reduced the inflammatory response. In addition, the number of beneficial genera (e.g., Bifidobacterium, Lactobacillus, and Odorobacterium) in the cecum of Wenchang chickens was significantly reduced after infection with S. Typhimurium. In this study, we revealed the structure of the cecal flora of Wenchang chickens infected with S. Typhimurium and demonstrated that S. Typhimurium can mediate the onset and development of intestinal inflammation through the activation of the metabolic pathway of ARA cyclooxygenase in Wenchang chickens. The results can provide data support and theoretical support for the prevention and control of avian salmonellosis.

Background: This study explored maternal gut, breast milk and infant gut microbiomes as possi-ble mediators of the observed effects of a relaxation intervention which reduced maternal stress and promoted infant weight gain. Methods: A randomized controlled trial was conducted in healthy Chinese primiparous mother-infant pairs. Mothers were randomly assigned to interven-tion group (IG, listening to relaxation meditation) or control group (CG). Outcomes were differ-ences in microbiome composition and diversity in maternal gut, breast milk and infant gut at 1- and 8-weeks between IG and CG, assessed by 16S rRNA gene amplicon sequencing of fecal and breastmilk samples. Results: 38 mother-infant pairs were included in this analysis (IG=19, CG=19). Overall microbiome community structure in the maternal gut was significantly different between IG and CG at 1-week and the difference was more significant at 8 weeks (Bray-Curtis distance R2=0.04 vs. R2=0.13). Post-intervention, the α-diversity was significantly lower in IG breast milk (observed features: CG=295 vs. IG=255, p=0.032); the Bifidobacterium genera presented higher relative abundance. In parallel, significantly higher α-diversity was observed in IG infant gut (observed features: CG=73 vs. IG=113, p

This review investigates the multifaceted role of the p66Shc adaptor protein and the gut microbiota in regulating mitochondrial function and oxidative stress, and their collective impact on the pathogenesis of chronic diseases. The study delves into molecular mechanisms by which p66Shc influences cellular stress responses through Rac1 activation, Forkhead-type transcription factors inactivation, and mitochondria-mediated apoptosis, alongside modulatory effects of gut microbiota-derived metabolites and endotoxins. Employing an integrative approach, the review synthesizes findings from a broad array of studies, including molecular biology techniques and analyses of microbial metabolites' impacts on host cellular pathways. The results underscore a complex interplay between microbial metabolites, p66Shc activation, and mitochondrial dysfunction, highlighting the significance of the gut microbiome in influencing disease outcomes through oxidative stress pathways. Conclusively, the review posits that targeting the gut microbiota-p66Shc-mitochondrial axis could offer novel therapeutic strategies for mitigating the development and progression of metabolic diseases. This underscores the potential of dietary interventions and microbiota modulation in managing oxidative stress and inflammation, pivotal factors in chronic disease etiology.

A compositional data vector is a special type of multivariate observation in which the elements of the vector are non-negative and sum to a constant, usually taken to be unity. A compositional data does not have zero and only retains relative information. Furthermore, comparisons can only be made between compositional data of the same component. The relevant sample space is the standard simplex. A simplex space is a space that is a generalized form of a triangle. For compositional data, many of the operations defined in Euclidean space are meaningless. Microbiome analyzes have become popular in recent years. Operational Taxonomic Units (OTU) and Amplicon Sequence Variants (ASVs) used in microbiome analysis are one type of compositional data. The microbiome data are counts of different species within a sample and it is compositional. Although there is an order of bacterial abundance within a sample, there is no order of bacterial abundance between samples. Firmicutes and Bacteroidetes, the major phyla in the colon, have been observed in humans worldwide. Gut microbiome analyses often use the Firmicutes/Bacteroidetes ratio and principal coordinates analysis (PCoA). Alpha and beta diversities are used as indicators of bacterial flora diversity. However, misinformation is pervasive in the human microbiome literature and analysis. There is a lot of misunderstanding regarding compositional data and its analysis. An attempt was made to demonstrate how to analyze using the “National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN JMD) (Public Data).” The results showed that PCoA did not work, and principal component analysis (PCA) was useful for analyzing the gut microbiome relative diversity.

Zn2+ has been implicated in the regulation of intestinal redox and microbial homeostasis, and we recently reported that transient receptor potential canonical (TRPC) 6 channel activity contributes to intracellular Zn2+ homeostasis in mammalian cells. This study aims to investigate the role of TRPC6-mediated Zn2+ influx in stress resistance of intestine. Expression profile of TRPC1-C7 mRNAs in the actively inflamed mucosa from inflammatory bowel disease (IBD) patients was analyzed using GEO database. Systemic TRPC3-knockout (KO) and TRPC6-KO mice were treated with dextran sulphate sodium (DSS) to induce colitis. The Zn2+ concentration and the mRNA expression levels of oxidative/inflammatory markers in colon tissues were quantitatively analyzed, and gut microbiota profiles were compared. TRPC6 mRNA expression level was increased in IBD patients and DSS-treated mouse colon tissues. DSS-treated TRPC6-KO mice, but not TRPC3-KO mice, showed severe weight loss and increased disease activity index compared with DSS-treated WT mice. The mRNA abundances of antioxidant proteins were basically increased in TRPC6-KO colon, with changes in gut microbiota profiles. Treatment with TRPC6 activator prevented the DSS-induced colitis progression accompanied by increasing Zn2+ concentration. We suggest that TRPC6-mediated Zn2+ influx activity plays a key role in stress resistance against IBD, providing a new strategy for treating colitis.