This work aimed to study the effect of repeated exposure to low doses of ozone on alpha-synuclein and the inflammatory response in the substantia nigra, jejunum, and colon. Seventy-two male Wistar rats were divided into six groups. Each group received one of the following treatments: The control group was exposed to air. Ozone groups were exposed for 7, 15, 30, 60, and 90 days for 0.25 ppm. for four hours daily. Afterward, they were anesthetized, and their tissues were extracted and processed using western blotting, immunohistochemistry, and qPCR. The results indicate a significant increase in alpha-synuclein in the substantia nigra and jejunum from 7 to 60 days of exposure, an increase in NFκB from 7 to 90 days in the substantia nigra, while in the jejunum, a significant increase is observed at 7 and 15 days and a decrease at 60 and 90 days for the colon. Interleukin IL-17 shows an increase at 90 days in the substantia nigra in the jejunum and increases at 30 days and in the colon at 15 and 90 days. Exposure to ozone increases the presence of al-pha-synuclein and the loss of regulation of the inflammatory response, which contributes significantly to degenerative processes.

Most research on colostrum quality and colostrum management focuses on maternal IgG transfer to the newborn calf. However, in addition to being a source of antibodies, colostrum has other components that influence passive immune transfer, nutrition, gut maturation, and thermoregulation. In this review, the constituents in the bovine colostrum, as well as their variation, are explored and it is discussed the biological role of colostrum on the newborn calf. Protein is the nutrient in higher concentration and fat is the nutrient with the most variation. There is a pronounced amplitude in the total solids content of colostrum, but the average concentration does not vary much between studies (24.7%). Bovine colostrum major components can vary with several factors, such as the region, season, breed, dry period length, and nutritional aspects of the dam. Bioactive components, cells, and microbiome variability are less understood, besides IgG. Regardless, they play crucial distinct roles in the physiological development of the newborn. However, a multi-interactive effect between these components, cells, and microorganisms is more likely to occur. Recently researched components in colostrum like miRNA, nucleo(t)sides, the milk fat globule membrane, oligosaccharides, minor proteins, and the microbiome are examples of promising interest areas of study.

Recent research has highlighted associations between sleep and microbial taxa and pathways. However, the causal effect of these associations remains unknown. To investigate this, we performed a two-sample bidirectional Mendelian randomization (MR) analysis using summary statistics of genome-wide association studies (GWAS) from 412 gut microbiome traits (N = 7,738) and GWAS studies from seven sleep-associated traits (N = 345,552 to 386577). We employed multiple MR methods to assess causality, with Inverse Variance Weighted (IVW) as the primary method. We further applied Cochran’s Q statistical analysis, MR-Egger intercept, and MR-PRESSO for heterogeneity and pleiotropy assessment, alongside a Bonferroni correction ((P

Introduction: Despite great advances in the treatment of oncological diseases, the development of medical technologies to prevent or reduce complications of therapy, in particular, those associated with surgery and the introduction of antibiotics remains relevant. The aim of the study: to evaluate the effectiveness of the use of autoprobiotics based on indigenous non-pathogenic strains of Enterococcus faecium and Enterococcus hirae in the complex therapy of colorectal cancer (CRC) in the early postoperative period. Materials and methods: A total of 36 patients diagnosed with CRC were enrolled in the study. The study group (Group A) comprised 24 CRC patients who received autoprobiotic therapy in the early postoperative period, while the control group (Group C) included 12 CRC patients without autoprobiotic therapy.Prior to surgery and between days 14-16 post-surgery, comprehensive evaluations were conducted on all patients, encompassing the following: stool and gastroenterological complains analysis. examination of the gut microbiota (bacteriological study, quantitative polymerase chain reaction, metagenome analysis), analysis of interleukins in serum. Results: The use of autoprobiotics led to decrease dyspeptic complaints after surgery, was associated with absence of postoperative complications, did not cause side effects, led to a decrease in the level of pro-inflammatory cytokines (IL-6 and IL-18) in the blood serum. The use of autoprobiotics led to positive changes in the structure of escherichia and enterococci populations, the elimination of Parvomonas micra, Fusobacterium nucleatum, decrease in the quantitative content of Clostridium perfringens, Akkermansia muciniphila. Metagenomic analysis (16S rRNA) revealed an increase in alpha diversity. Conclusion: The administration of autoprobiotics in the postoperative period is highly effective and safe in the comprehensive treatment of colorectal cancer patients. Future studies will allow the discovery of additional fine mechanisms of autoprobiotic therapy and its impact on the digestive, immune, endocrine and neural systems.

In the world, migraine is one of the most common cause of disability in adults. To date, there is no a single cause for this disorder, but rather a set of physio-pathogenic triggers, in combination with a genetic predisposition. Among factors related to the migraine onset, a crucial role seems to be played by gut dysbiosis. In fact, it has been demonstrated how the intestine is able to modulate the central nervous system activities, through the gut-brain axis, and how gut dysbiosis can influence neurological pathologies, including migraine attacks. In this contest, in addition to migraine conventional pharmacological treatments, attention has been paid to an adjuvant therapeutic strategy based on different nutritional approaches and lifestyle changes able to positively modulate the gut microbiota composition. In fact, the restoration of the balance between the different gut bacterial species, the reconstruction of the gut barrier integrity and the control of the release of gut-derived inflammatory neuropeptides, obtained through specific nutritional patterns and lifestyle changes, represent a possible beneficial additive therapy for many migraine subtypes. Herein, this review explores the bi-directional correlation between migraine and the main chronic non-communicable diseases, like diabetes mellitus, arterial hypertension, obesity, cancer and chronic kidney diseases, whose link is represented by gut dysbiosis.

Insulin signaling plays a crucial role in cellular uptake of glucose and different metabolic pathways. Impairment in cellular insulin sensitivity due to various molecular pathways leads to Insulin resistance (IR) as well as fatty liver. In this review, mechanisms by which zinc involved in decreasing IR are described, focusing on oxidative stress, inflammation, immune system, gut flora and hepatic lipophagy. This study reviews the cause of IR and highlights the role of zinc in mechanisms diminishing IR and fatty liver.

The effect of defatted Hermetia illucens meal (HIM) dietary inclusion on growth performance, stress indicators and gut histological traits of Sparus aurata was studied. For 131 days, 312 fish were fed with one basal diet, containing fish meal as animal protein source, and three diets containing 25%, 35% and 50% HIM as a partial replacement for fishmeal. On all fish (26 fish per tank, 3 replicate tanks per diet, 78 fish per diet) the growth performance were calculated. At the end of the trial, on a subsample of 72 specimens (6 fish per tank, 3 replicate tanks per diet, 18 fish per diet), stress parameters were determined on blood samples and gut histological tract investigated. Insect meal inclusion did not affect (p > 0.05) growth performance, blood parameters, length and width of villi and goblet cell count of the posterior gut tract while, those of the anterior gut tract while increased (p < 0.05). The histological examination of the intestinal sections showed in fish fed the HIM25 and HIM50 diets, more frequent and evident morphological changes; instead, there were no substantial differences between HIM0 and HIM35 groups. In conclusion, the HIM35 was the most tolerated formulation by fish.

Gut dysbiosis, alongside with high-fat diet and cigarette smoking, is considered one of the factors promoting coronary arterial disease (CAD) development. The present study aimed to research whether gut dysbiosis can increase bacterial metabolites concentration in the blood of CAD patients and what impact these metabolites can exert on endothelial cells. The gut microbiome of 15 CAD patients and age-matched 15 healthy controls was analyzed by metagenome sequencing. The in vitro impact of LPS and indoxyl sulfate at concentrations present in patients sera on endothelial cells was investigated. A metagenome sequencing analysis revealed gut dysbiosis in CAD patients, further confirmed by elevated levels of LPS and indoxyl sulfate in patients sera. CAD was associated with depletion of Bacteroidetes and Alistipes. LPS and indoxyl sulfate in meager concentrations demonstrated co-toxicity to endothelial cells inducing reactive oxygen species, E-selectin, and monocyte chemoattractant protein-1 (MCP-1) production and promoting thrombogenicity of endothelial cells confirmed by monocyte adherence. The co-toxicity of LPS and indoxyl sulfate was associated with harmful effects on endothelial cells, strongly suggesting that gut dysbiosis-associated increased intestinal permeability can initiate or promote endothelial inflammation and atherosclerosis progression.

Eukaryotic enteric pathogens (EEP) are a public health issue in tropical areas. Yet, their interactions with the gut mycobiota remain poorly understood. We conducted a cross-sectional study in Malian children to analyze the impact of EEP on the gut fungal community. EEP were assessed by qPCR and the gut mycobiota was characterized by ITS1-2 metabarcoding in stool samples collected from 296 children. The 100 controls, in whom no EEP was detected, were compared to: a) 196 children with ≥1 EEP; b) 91 with only Blastocystis; c) 35 with only Giardia intestinalis; and d) 12 with another (&lt;1% each) EPP. The gut fungal community structure was homogenous in each children’s group. Linear size-effect discriminant analysis highlighted five relatively more abundant species, including Fusarium longipes and Penicillium caseifulvum, in children with ≥1 EEP, whereas 28, including Aspergillus sydowii and Microdochium colombiense were more abundant in controls. Fusarium, Pyxidiophora, and Stereum abundance was higher in Blastocystis-infected children, whereas Ogataea and Allocryptovalsa were more abundant in controls. Sordariales and Mortierellales abundance was higher in Giardia intestinalis-infected children, whereas Agaricales and Capnodiales abundance was higher in controls. In conclusion, EEP do not significantly alter the gut fungal community structure, and further studies are warranted to confirm our findings that particular taxa are associated with susceptibility or resistance to specific EEP.

The present study was conducted to evaluate encapsulated essential oils as an alternative anticoccidial in coccidiosis vaccine challenged broiler chickens. A total of 600 day-old male broiler chicks were provided with no-added corn-soybean meal-based control diet or diets that contained either salinomycin or EO at 60 and 120 mg per kg of diet. On day 21, half of the control groups were orally challenged with a coccidiosis vaccine at 25 times higher than the recommended vaccine dose. During 22 to 28 days (i.e., one-week post coccidiosis vaccine challenge), the challenged chickens had decrease (P < 0.05) in body weight gain and feed intake but increase in feed conversion ratio compared with the non-challenged, naïve control chickens. However, dietary EO significantly counteracted (P < 0.05) coccidiosis vaccine-induced depression in body weight gain and feed intake. Increasing dietary EO linearly decreased (P < 0.05) the concentrations of the volatile fatty acids. Dietary SAL and EO affected gut morphology in chickens at 20 days posthatch. Increasing dietary EO linearly (P = 0.073) increased serum catalase activity. Collectively, our study shows that dietary EO increased coccidiosis vaccine-induced growth depression and altered gut physiology in broiler chickens.

The combination of freeze-dried aronia, red ginseng, ultraviolet-irradiated shiitake mushroom and natokinase (AGM; 3.4: 4.1: 2.4: 0.1) was examined to evaluate its effects on insulin resistance, insulin secretion and gut microbiome in a non-obese type 2 diabetic animal model. Pancreatectomized (Px) rats were provided high fat diets supplemented with either of 1) 0.5 g AGM (AGM-L), 2) 1 g AGM (AGM-H), 3) 1 g dextrin (control), or 4) 1g dextrin with 120 mg metformin (positive-control) per kg body weight for 12 weeks. AGM (1 g) contained 6.22 mg cyanidin-3-galactose, 2.5 mg ginsenoside Rg3 and 0.6 mg β-glucan. Px rats had decreased bone mineral density in the lumbar spine and femur and lean body mass in the hip and leg compared to the normal-control and AGM-L and AGM-H prevented the decrease. Visceral fat mass was lower in the control group than the normal-control group and its decrease was smaller by AGM-L and AGM-H. HOMA-IR was lower in descending order of the control, positive-control, AGM-L, AGM-H and normal-control groups. Glucose tolerance was deteriorated in the control group and it was improved by AGM-L and AGM-H more than in the positive-control group. Glucose tolerance is associated with insulin resistance and insulin secretion. Insulin tolerance indicated insulin resistance was highly impaired in diabetic rats, but it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Insulin secretion capacity, measured by hyperglycemic clamp, was much lower in the control group than the normal-control group and it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Diabetes modulated the composition of gut microbiome and AMG prevented the modulation of gut microbiome. In conclusion, AGM improved glucose metabolism by potentiating insulin secretion and reducing insulin resistance in insulin deficient type 2 diabetic rats. The improvement of diabetic status alleviated body composition changes and prevented changes of gut microbiome composition.

IBD, encompassing CD and UC, are characterized by chronic gastrointestinal inflammation due to abnormal immune responses to gut microflora. The bidirectional communication between the gut and the brain, known as the GBA, is disrupted in IBD, leading to neurobiological imbalances and affective symptoms. Systemic inflammation in IBD affects the brain's inflammatory response system, hormonal axis, and BBB integrity, influencing gut microbiota and clinical responses to probiotics. This review aims to explore the links between dysregulations in the GBA, serum biomarkers, and the development of MCI and NDDs. The objective is to identify potential correlations and propose future research directions to understand the impact of altered microbiomes and intestinal barrier functions on NDDs. Studies suggest a potential link between IBD and extraintestinal complications such as MCI and NDDs. Mechanisms include systemic inflammation, BBB dysfunction, autoimmune responses, GBA dysfunction, medication effects, and comorbidities. Serum biomarkers, including vitamin D3, C-reactive protein, high-sensitivity C-reactive protein, vitamin B12, homocysteine, serum amyloid, neuron-specific enolase, neurofilament light chain, S100 proteins, brain-derived neurotrophic factor, IL-6, LP-2 associated phospholipase, prostaglandin E2, IL-1β, and TNF-α, have been investigated for their potential to predict MCI but current results are lacking clarity.

Honey bee (Apis mellifera) health is crucial for honey bee products, and effective pollination and is closely associated with gut bacteria. Various factors such as reduced habitat, temperature, disease, and diet affect the health of honey bees, by disturbing the homeostasis of the gut microbiota. In this study, high-throughput 16S rRNA gene sequencing was used to analyze the gut microbiota of Apis mellifera subjected to seven different diets. The identified microbiota in the Apis mellifera gut from all the diets consisted of Lactobacillus (62%), followed by Rhizobiaceae (21%), Snodgrassella (4%), and Erwiniaceae (4%) among other 33 genera. Based on diet types, Lactobacillus a lactic acid bacteria (LAB), dominates the microbiota with the highest relative abundance in AIGT+SAC (91%), AIGT+Soytide (88%), and AIGT+Apple juice (69%) diet groups. Bifidobacterium and Commensalibacter appeared as the second most abundant genera in AIGT+SAC and AIGT+Soytide diet groups, respectively. These bacteria are important markers for honey bee health. Considering the importance of these diets in shaping their host microbiome into a healthy status. Individual honey bee health (IHH) was observed to validate the quality and correlation between the microbiota and honey bee health. The results were consistent, indicating that Apis mellifera fed on AIGT+Soytide and AIGT+SAC diet showed the highest health expression level of vitellogenin. The group with 60%Syrup possessing Rhizobiaceae as the dominant taxa showed poor health status. This finding paved the way for establishing a link between gut microbiota and IHH under different diets.

Despite substantial heterogeneity of studies, there is evidence that antibiotics commonly used in primary care influence the composition of the gastrointestinal microbiota in terms of changing the composition and/or diversity. Benzyl isothiocyanate (BITC) from the food and medicinal plant nasturtium (Tropaeolum majus) is known for its antimicrobial activity and is used for the treatment against infections of the draining urinary tract and upper respiratory tract. Against this background, we raised the question whether 14 d nasturtium intervention (3 g daily, N=30 healthy females) could also impact the normal gut microbiota composition. Spot urinary BITC excretion highly correlated with a weak, but significant antibacterial effect against Escherichia coli. A significant increase in human beta defensin 1 as parameter for host defense was seen in urine and exhaled breath condensate (EBC) upon verum intervention. Pre-to-post analysis revealed that mean gut microbiome composition did not significantly differ between groups, nor did circulating serum metabolome. On an individual level, partly large changes were observed between sampling points, though. Explorative Spearman rank correlation analysis in subgroups revealed associations between gut microbiota and the circulating metabolome, as well as between changes in blood markers and bacterial gut species.

Abstract: Autism spectrum disorders (ASDs) are complex, lifelong, neurodevelopmental conditions of largely unknown cause. The global prevalence of autism has increased twentyfold to thirtyfold since the earliest epidemiologic studies were conducted in the late 1960s and early 1970s. Recent reports agree on the association of ASD with the alteration of the microbiome (dysbiosis), which raises the possible role of external factors. Our study aimed at identifying antibiotic classes that might be associated with the development of ASD-related dysbiosis either promoting or inhibiting the process. Statistical comparison was made between the average yearly consumption of different antibiotic classes (1997-2020) and the number of individuals living with ASD estimated for 2023/100000 population in 30 European countries and the results were statistically analyzed. Tetracycline (J01A) showed significant positive (promoting) association with the prevalence of ASD (Pearson r: 0.373, p: 0.043. OR: 1.312, CI95%: 0.995-1.791, p: 0.065) and narrow-spectrum, beta-lactamase resistant penicillin (J01CF) (Pearson r: 0.524, p: 0.003, OR: 3.240, CI95%: 1.710-8.853, p: 0.004, Kruskal-Wallis p: 0.032). Mild, negative (inhibitory) association was observed with broad-spectrum, beta-lactamase sensitive penicillin (J01CA) (Pearson r: -0.278, p: 0.157, OR: 0.808, CI95%: 0649-0957, p: 0.028) and narrow-spectrum, beta-lactamase-sensitive penicillin (J01CE) (Pearson p: -0.032, r: 0.865, OR: 0.725, CI95%: 0.543-0.885, p: 0,009). Our findings strongly support the animal experiments when penicillin-exposed newborn mice developed "autism-like" behavior.

Background: Abdominal migraine (AM) is a clinical diagnosis specified by Rome IV and ICHD III as a functional gastrointestinal disease (FGID) and a migraine associated syndrome, respectively. AM is undiagnosed and undertreated, and thus far the FDA has not approved any drug for AM treatment. We and others showed that changes in the kynurenine (KYN) pathway of tryptophan (TRP) metabolism played an important role in the pathogenesis and treatment of FIGDs. Changes in the KYN pathway were shown in migraine. Findings: Abdominal migraine reflects impairments in communication within the gut-brain axis. Treatment approaches have not been sufficiently documented and are based on experience of physicians, presenting personal rather than evidence-based practice and including efficacy of some drugs used in adult migraine. Non-pharmacological treatment of AM is aimed preventing or ameliorating AM triggers. Modulations within the KYN pathway of TRP metabolism induced by changes in TRP content in the diet, may ameliorate FGIDs and support their pharmacological treatment. Pharmacological manipulations of brain KYNs in animals have brought promising results for clinical applications. Conclusions: In conclusion, controlled placebo-based clinical trials with dietary manipulation to adjust the amount of the product of the KYN pathway of TRP metabolism are justified in children and adolescents with AM. Further preclinical studies are needed to establish details of these trials.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterised by poor social interaction and communication, as well as restricted and stereotyped interests. Due of the high prevalence of gastrointestinal disorders in individuals with ASD, researchers have investigated the gut microbiota as a potential contributor to its aetiology. The relationship between the microbiome, gut, and brain (microbiome-gut-brain axis) has been acknowledged as a key factor in modulating brain function and social behaviour, but its connection to the aetiology of ASD is not well understood. Recently, there has been increasing attention on the relationship between the immune system, gastrointestinal disorders, and neurological issues in ASD, particularly in relation to the loss of specific species or a decrease in microbial diversity. It focuses on how gut microbiota dysbiosis can affect gut permeability, immune function, and microbiota metabolites in ASD. Although a very complete study suggests that dysbiosis is a consequence of the disease and that it has practically no effect on autistic manifestations. This is a review of the relationship between the immune system, microbial diversity, and the microbiome-gut-brain axis in the development of autistic symptoms severity and, a proposal of a novel role of gut microbiome in ASD, where dysbiosis is a consequence of ASD-related behaviour and where dysbiosis in turn accentuates the autistic manifestations of the patients via microbiome-gut-brain axis in a feedback circuit.

Red palm weevils (RPWs) are a major pest to coconut and palm trees, causing significant economic losses in many countries. The current control method involves using insecticides, which are unsustainable and environmentally damaging. Thus, it is necessary to develop an eco-friendly and sustainable approach to mitigate the RPW problem. Our studies have revealed that feeding RPWs with food containing specific herbs can affect the weevils' mutualistic relationship with gut microbiota or their growth hormones, resulting in a notable reduction in the metamorphosis rate at the pupation stage. For instance, the addition of Kra-jeab (a roselle Hibiscus sabdariffa) and Kra-pao (a holy basil Ocimum tenuiflorum) led to a reduction of 76.7% and 75.6%, respectively, in the metamorphosis rate, while combining the two herbs resulted in a higher reduction rate of 86.7%. In addition to these findings, altering their pupation nature by reducing the fiber length used in RPW feed to less than 1 centimeter can stop the weevil’s pupation entirely. These findings demonstrate the potential application of biological and physical factors to reduce RPWs' metamorphosis rate and control their destructive impact on palm industries, thus providing a promising solution for the conflict between palm and insect farmers.

The “Gut-Liver Axis” refers to physiological bidirectional interplay between the gut and its microbiota and the liver which, in health, occurs thanks to a condition of immune tolerance. In recent years, several studies have shown that, in case of modifications of gut bacterial homeostasis or impairment of intestinal barrier functions, cholangiocytes, which are the epithelial cells lining the bile ducts, activate innate immune responses against gut-derived microorganisms or bacterial products that reach the liver via enterohepatic circulation. Intestinal dysbiosis or impaired intestinal barrier functions expose cholangiocytes to an increasing amount of microorganisms and may exacerbate inflammatory responses thus leading to fibrotic remodeling of the organ. The present review focuses on the role of the gut liver axis in the pathogenesis of cholangiopathies.

Dietary factors play an important role in shaping the gut microbiome which, in turn, regulates the molecular events in colonic mucosa. The composition and resulting metabolism of the gut microbiome have been implicated in the development of colorectal cancer (CRC). Diets low in dietary fibers and phytomolecules as well as other lifestyle-related factors may predispose to CRC. Emerging evidence demonstrates that the predominance of microbes, such as Fusobacterium nucleatum, can predispose the colonic mucosa to malignant transformation. Dietary and lifestyle modifications have been demonstrated to restrict the growth of potentially harmful opportunistic organisms. In this study, we aim to present evidence regarding the relationship of dietary factors to the gut microbiome and development of CRC.

Plants and plant-derived food products have been used for medicinal purposes since the ancient. Medicinal Plant-based functional foods or plant-based dietary compounds are a re-emerged interest for their therapeutic benefits and nutritive supports which has implicated in healthcare systems across the world. Neurological disorders are one of the greatest threats to public health and according to the World Health Organization, about 100 million people are affected globally by several neurological and mental ailments. In a traditional medication system, medicinal plants have been applied as both neuro-therapeutic purposes and micro-macro nutrients provider for the wellbeing of psychological states e.g. anti-depressant, anti-anxiety, anti-convulsions, anti-dementia, anti-psychotic, etc. Herein, it is a topic of great interest to present a conceptual aspect by reviewing relevant scientific literature about the plant-based functional foods or bioactive phytochemicals for the prevention and treatment of mental and neurological disorders. From the literature assessment, we have found that nutritional neuroscience is becoming an advanced research discipline and there has been a growing pile of evidence concerning the therapeutic use of plant-based functional foods and/or plant-derived food compounds for the management of neurologic health, evolving with promising impact over the time.

Autoimmune kidney diseases arise from a loss of tolerance to antigens, often with unclear triggers. In this review we explore the role of the gut microbiome and how disease, diet and therapy can alter the gut microbiota consortium. Perturbations in the gut microbiota may induce the translocation of microbiota-derived inflammatory molecules such as liposaccharide (LPS) and other toxins systemically by penetrating the gut epithelial barrier. Once in the blood stream these pro-inflammatory mediators activate immune cells which release pro-inflammatory molecules many of which are antigens in autoimmune diseases. The ratio of gut bacteria Bacteroidetes:Firmicutes is associated with worse outcomes in multiple autoimmune kidney diseases including Lupus nephritis, MPO-ANCA vasculitis and Goodpasture’s syndrome. Therapies which enhance short chain fatty acid (SCFA)-producing bacteria in the gut have powerful therapeutic potential. Dietary fibre is fermented by gut bacteria which in turn release SCFAs which protect the gut barrier as well as modulate immune responses towards a tolerogenic anti-inflammatory state. Herein, we describe where the current field of research is and the strategies to harness the gut microbiome as potential therapy.

Distal Sensory Peripheral Neuropathy (DSP) is a common complication in HIV-infected individ-uals, leading to chronic pain and reduced quality of life. Despite antiretroviral therapy (ART), DSP persists, often prompting the use of opioid analgesics, which can paradoxically worsen symptoms through opioid-induced microbial dysbiosis. This study employs the HIV Tg26 mouse model to investigate HIV-DSP development and assess gut microbiome changes in response to chronic morphine treatment and ART using 16s rRNA sequencing. Our results reveal that chronic morphine and ART exacerbate HIV-DSP in Tg26 mice, primarily through mechanical pain path-ways. As the gut microbiome may be involved in chronic pain persistence, microbiome analysis indicated distinct bacterial community changes between WT and Tg26 mice as well as morphine and ART-induced microbial changes in the Tg26 mice. This study reveals the Tg26 mice model to be a relevant system that can help elucidate the pathogenic mechanisms of opioid and ART-induced exacerbation of HIV-associated pain. Our results shed light on the intricate inter-play between HIV infection, ART, opioid use, and the gut microbiome in chronic pain development. They hold implications for understanding the mechanisms underlying HIV-associated pain and microbial dysbiosis, with potential for future research focused on prevention and treatment strategies.

The makeup of human microbiota has been linked to a number of autoimmune disorders. Recent developments in whole metagenome sequencing and 16S rRNA sequencing technology have considerably aided research into the microbiome and its relationship to disease. Due to the inherent high dimensionality and complexity of data generated by high-throughput platforms, conventional bioinformatics techniques could only provide an inadequate explanation for the most relevant changes and seldom provide correct predictions. Machine learning, on the other hand, is a subset of artificial intelligence applications that enable the untangling of high-dimensional systems and intricate knots in correlation by learning complex patterns and improving automatically from training data without being explicitly programmed. Machine learning is increasingly being utilized to research the influence of microbes on the onset of illness and other clinical features since computer power has increased dramatically in the last few decades. In this review paper, we focused on emerging methodological approaches of supervised machine learning algorithms for identification of autoimmune disorders utilizing metagenomics data, as well as the potential benefits and limitations of machine learning models in clinical applications.

Apicomplexan infections, such as giardiasis and cryptosporidiosis, negatively impact a considerable proportion of human and commercial livestock populations. Despite this, the molecular mecha-nisms of disease, particularly the effect on the body beyond the gastrointestinal tract, are still poorly understood. To highlight host-parasite-microbiome biochemical interactions, we utilised integrated metabolomics-16S rRNA genomics and metabolomics-proteomics approaches in a C57BL/6J mouse model of giardiasis and compared these to Cryptosporidium and uropathogenic Escherichia coli (UPEC) infections. Comprehensive samples (faeces, blood, liver, and luminal contents from duo-denum, jejunum, ileum, caecum and colon) were collected 10 days post infection and subjected to proteome and metabolome analysis by liquid and gas chromatographic mass-spectrometry, re-spectively. Microbial populations in faeces and luminal washes were examined using 16S rRNA metagenomics. Proteome-metabolome analyses indicated that 12 and 16 key pathways were sig-nificantly altered in the gut and liver, respectively, during giardiasis with respect to other infections. Energy pathways including glycolysis and supporting pathways of glyoxylate and dicarboxylate metabolism, and redox pathway of glutathione metabolism, were upregulated in small intestinal luminal contents and the liver during giardiasis. Metabolomics-16S rRNA genetics integration in-dicated that populations of three bacterial families –Autopobiaceae (Up), Desulfovibrionaceae (Up) and Akkermanasiaceae (Down) – were most significantly affected across the gut during giardiasis, causing upregulated glycolysis and short-chained fatty acid (SCFA) metabolism. In particular, the perturbed Akkermanasiaceae population seemed to cause oxidative stress responses along the gut-liver axis. Overall, the systems biology approach applied in this study highlighted that the effects of host-parasite-microbiome biochemical interactions extended beyond the gut ecosystem to the gut-liver axis. These findings form the first steps in a comprehensive comparison to ascertain the major molecular and biochemical contributors of host-parasite interactions and contribute towards the development of biomarker discovery and precision health solutions for apicomplexan infections.

Hazardous toxic metals, such as lead and cadmium, and to a lesser extent aluminum, are extensively recognized as detrimental for health following ingestion within food and water, or following inhalation. Gut and food-derived microbes, by interacting with heavy metals, may actively or passively modulate their bioavailability inside the gut, either by adsorption or by sequestration. Such a bioremediation within the gut implies the selection of safe microbes, based on their specific capacities to immobilize metals. We investigated the metal removal ability of 225 bacteria toward the potential harmful trace elements lead, cadmium and aluminum in vitro, using Inductively Coupled Plasma Mass Spectrometry analysis. Interspecies and intraspecies comparisons were addressed and discussed among bacteria from the phylum Firmicutes, which are mostly lactic acid bacteria, including Lactobacillus spp, with some Lactococcus, Pediococcus and Carnobacterium representatives, Actinobacteria as well as Proteobacteria. The effect on mixture of lead and cadmium was also investigated. Although the purpose of such a screening is so far not to elucidate each of the various strain specific- and metal dependent- mechanisms of heavy metal removal, we identified potential bacteria which are able to alleviate Pb(II) and Cd(II) concerns in order to propose performing candidate probiotics for metal xenobiotic bioremediation.

Spondyloarthritis comprises of a group of inflammatory diseases of the joints and spine with various clinical manifestations. The group includes ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthritis. The exact etiology and pathogenesis of spondyloarthritis are still unknown, but five hypotheses explaining the pathogenesis exist. These hypotheses suggest that spondyloarthritis is caused by arthritogenic peptides, an unfolded protein response, HLA-B27 homodimer formation, malfunctioning endoplasmic reticulum aminopeptidases, and, last but not least, gut inflammation and dysbiosis. Here we discuss the five hypotheses and the evidence supporting each. In all of these hypotheses, HLA-B27 plays a central role. It is likely that a combination of these hypotheses, with HLA-B27 taking center stage, will eventually explain the development of spondyloarthritis in predisposed individuals.

Major depression (MDD) is accompanied by higher serum IgM/IgA responses to LPS of Gram-negative bacteria, suggesting increased bacterial translocation and gut dysbiosis. Gut dysbiosis may occur in bipolar disorder (BD) and there are differences between MDD and BD type 1 (BP1) and -2 (BP2) in nitro-oxidative stress biomarkers associated with leaky gut. This study examines serum IgM/IgA responses directed to LPS of 6 Gram-negative bacteria in 29 BP1, 37 BP2, 44 MDD and 30 healthy individuals. MDD plus BD was best discriminated from controls by increased IgM/IgA responses to Pseudomonas aeruginosa. BP1 patients showed higher IgM responses to Morganella morganii as compared with MDD and BP2 patients. Patients with melancholia showed higher IgA responses to Citrobacter koseri as compared to controls and non-melancholic depression. The total score on the Hamilton Depression Rating Scale was significantly associated with IgA responses, especially C. koseri. IgG responses to oxidized low-density lipoprotein were significantly associated with signs of increased bacterial translocation. In conclusion, not only MDD but also BP1 and BP2 are accompanied by an immune response due to the increased load of plasma LPS of gut commensal bacteria while these aberrations in the gut-brain axis are most pronounced in BP1 and patients with melancholic features. Activated oxidative stress pathways and autoimmune responses to oxidative specific epitopes in mood disorders may be driven by a breakdown in gut paracellular, transcellular and/or vascular pathways. If replicated, drugs that protect the integrity of the gut barrier may offer novel therapeutic opportunities for BP1 and MDD.

The farnesoid X receptor (FXR)/βKlotho/fibroblast growth factors (FGFs) pathway is crucial for maintaining the intestinal barrier and preventing colorectal cancer (CRC). We used an FXR ago-nist, GW4064, and FXR knockout (KO) mice to investigate the role of FXR/Klothos/FGFs pathways in lipopolysaccharide (LPS)-induced intestinal barrier dysfunction and colon carcinogenesis. The results showed that upregulation of FXR in enterocytes effectively ameliorated intestinal tight junction markers (claudin1, Zonula occludens-1), inflammation, and bile acid levels, thereby protecting mice from intestinal barrier dysfunction and colon carcinogenesis. GW4064 treatment increased FXR, αKlotho, βKlotho, FGF19, FGF21, and FGF23 in wild-type mice exposed to LPS, while FXR KO mice had decreased levels. FXR KO mice exhibited elevated colon cancer markers (β-catenin, LGR5, CD44, CD34, Cyclin D1) under LPS, underscoring the pivotal role of FXR in inhibiting the development of colon tumorigenesis. The varying gut microbiota responses in FXR KO mice versus wild-type mice post-LPS exposure emphasize the pivotal role of FXR in pre-serving intestinal microbial health, involving Bacteroides thetaiotaomicron, Bacteroides acidifaciens, and Helicobacter hepaticus. Our study validates the effectiveness of GW4064 in alleviating LPS-induced disruptions to the intestinal barrier and colon carcinogenesis, emphasizing the importance of the FXR/αKlotho/βKlotho/FGFs pathway and the interplay between bile acids and gut microbiota.

Research conducted on individuals with depression reveals that major depressive disorders (MDDs) coincide with diminished levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain, as well as modifications in the subunit composition of the primary receptors (GABAA receptors) responsible for mediating GABAergic inhibition. Furthermore, there is substantial evidence supporting the significant role of GABA in regulating stress within the brain, which is a pivotal vulnerability factor in mood disorders. Although there is substantial evidence indicating that GABA may be affecting GABA receptors in peripheral tissues, there is comparatively less evidence supporting its direct action within the brain. Emerging evidence highlights that GABA may exert beneficial effects on the brain and psyche through the gut-brain axis. GABA is readily available and approved as a food supplement in many countries. While GABA enjoys wide consumer acceptance in Eastern Asian markets, with many consumers reporting favorable effects on stress regulation, mood, and sleep, rigorous independent research is still largely lacking. Basic research, coupled with initial clinical findings, makes GABA an intriguing neuro-nutritional compound deserving of clinical studies in individuals with depression and other psychological problems.

Background: IBD is a spectrum of pathologies characterized by dysregulated immune activation leading to uncontrolled response against intestinal, thus resulting in chronic gut inflammation and tissue damage. Due to its complexity, the molecular mechanisms responsible for disease onset and progression are still elusive, thus requiring intense research effort. In this context, the development of models recapitulating the etiopathology of IBD is critical.Methods: Colon from C57BL/6 or BALB/c mice were cultivated in a gut-ex-vivo system (GEVS), exposed 5h to DNBS 1,5 or 2,5 mg/ml, and the main hallmarkers of IBD were evaluated.Results: Gene expression analysis revealed a DNBS-induced: i) compromised Tight junction organization, responsible for tissue permeability dysregulation; induction of ER stress, and iii) tissue inflammation in colon of C57BL/6 mice. Moreover, the concomitant DNBS-induced apoptosis and ferroptosis pathways was evident in colon from both BALB/c and C57BL/6 mice.Conclusions: Overall, we have provided results demonstrating that GEVS is a consistent, reliable, and cost-effective system for modeling DNBS-induced IBD, useful for studying the onset and progression of human disease at the molecular level, while also reducing animal suffering.

In the last three decades, the robust scientific data emerged, demonstrating that the immune-inflammatory response is a fundamental component of the pathophysiology of major depressive disorder (MDD). Psychological stress and various inflammatory comorbidities contribute to such immune activation. Still, this is not uncommon that patients with depression do not have defined inflammatory comorbidities, and alternative mechanisms of immune activation need to take place. The gastrointestinal (GI) tract, along with gut-associated lymphoid tissue (GALT), constitutes the largest lymphatic organ in the human body and forms the biggest surface of contact with the external environment. It is also the most significant source of bacterial and food-derived antigenic material. There is a broad range of reciprocal interactions between the GI tract, intestinal microbiota, increased intestinal permeability, activation of immune-inflammatory response, and the CNS that has crucial implications in brain function and mental health. This intercommunication takes place within the microbiota-gut-immune-glia (MGIG) axis, and glial cells are the main orchestrator of this communication. A broad range of factors, including psychological stress, inflammation, dysbiosis and other, may compromise the permeability of this barrier. This leads to excessive bacterial translocation and the excessive influx of food-derived antigenic material that contributes to activation of the immune-inflammatory response and depressive psychopathology. This chapter summarizes the role of increased intestinal permeability in MDD and mechanisms of how the "leaky gut" may contribute to immune-inflammatory response in this disorder.

Identifying appropriate animal models is critical in developing translatable in vitro and in vivo systems for therapeutic development and investigating disease pathophysiology. These animal models should have direct biological and translational relevance to the underlying disease they are supposed to mimic. Aging dogs naturally develop a cognitive decline in many aspects including learning and memory, but also exhibit human-like individual variability in the aging process. Neurodegenerative processes that can be observed in both human and canine brains include the progressive accumulation of β-amyloid (Aβ) found as diffuse plaques in the prefrontal cortex, including the gyrus proreus, the hippocampus, and in the cerebral vasculature. A growing body of epidemiological data shows that human patients with neurodegenerative diseases have concurrent intestinal lesions, and histopathological changes in the gastrointestinal (GI) tract occurs decades that evolve before neurodegenerative changes. Gut microbiome alterations also have been observed in many neurodegenerative diseases including Alzheimer’s and Parkinson’s diseases, and inflammatory CNS diseases. Interestingly, only recently has the dog gut microbiome been recognized to more closely resemble in composition and in functional overlap with the human gut microbiome as compared to rodent models. This article aims to review the physiology of the gut-brain axis (GBA), and its involvement with neurodegenerative diseases in dogs and humans. Additionally, we outline the advantages and disadvantages of traditional in vitro and in vivo models and discuss future research directions investigating major human neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases using dogs.

(1) The present study investigated the effect of orally administered Limosilactobacillus fermentum HY7302 (HY7302) on the relationship between ocular tissue and the microbiome in the corneal injured dry eye mice model. (2) 0.1% benzalkonium chloride (BAC) was applied to the ocular surface for 14 days to induce corneal injury in male Balb/c mice. During the BAC treatment period, HY7302 (1 × 108 CFU/kg/day or 1 × 109 CFU/kg/day) or omega-3 positive control (200 mg/kg/day) were administered orally (n = 8/group). To examine signaling pathways affected by HY7302 treatment, the in vitro effects of HY7302 on tight junctions and the inflammatory response were investigated in a mouse colon epithelial cell line, CMT-93. (3) BAC exposure decreased tear production, induced ocular inflammation and corneal epithelial detachment, and altered gut microbiota. However, oral administration of HY7302 restored tear secretion and decreased corneal epithelial detachment in BAC-treated corneal injury mice. Further, HY7302 alleviated corneal inflammation via modulation of matrix metalloproteinase-9 (MMP-9) expression and alterations in gut microbiota composition. (4) These findings suggest that the gut–eye axis interaction between gut microbiota and eye tissue affects disease severity in corneal injury, and that alteration of the microbiota by HY7302 could improve eye health by regulating the inflammatory response.

Background: Post-delivery period could be characterized by psychological distress (e.g., anxiety, sadness, and irritability), leading to post-partum depression (PPD). Objective: The present clinical study assess the effect of probiotic supplementation containing Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 (4x10⁹ CFU/day) on mother’s mood and breastfeeding quality during the first trimester after delivery. Methods: A Randomized Double Blind Controlled (RDBPC) trial has been carried out in 200 healthy new mothers divided into an active group taking a supplement containing Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 (4x10⁹ CFU/day) plus multivitamins, and a control group (multivitamin complex only) for 90 days. Symptoms related to maternal depression and breastfeeding quality were evaluated at days 45 and 90 by Edinburgh Postnatal Depression Scale (EPDS) and Breastfeeding Self-Efficacy Scale Short-Form (BSES-SF). Results: At days 45 and 90, probiotic treatment significantly ameliorated the mothers’ mood compared to the control treatment (p<0.001). Likewise, breastfeeding quality and baby’s cries significantly improved in the probiotic group (p<0.001). Conclusions: Microbiota alterations could influence post-delivery woman’s mental state. According to our results, L. reuteri PBS072 and B. breve BB077 are potential candidates able to improve stress resilience in the post-partum period.

Increasing clinical and preclinical evidences implicate gut microbiome (GM) dysbiosis as a key susceptibility factor for neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s diseases (PD). In recent years, neurodegenerative diseases have not been viewed as driven solely by defects in brain, and the role of GM in modulating the central nervous system function via gut-brain axis has attracted considerable interest. Encouraged by GM researches, the next-generation probiotics may lead to tangible impacts on the treatment of neurodegenerative disorders. This review summarizes the current understandings of GM composition and characteristics associated with neurodegenerative diseases, and the demonstrations of molecules from GM affecting neurodegeneration. Particularly, applications of next-generation probiotics such as Clostridium butyricum, Akkermansia muciniphila, Faecalibacterium prausnitzii, and Bacteroides fragilis for remediation of neurodegenerative diseases are discussed.

This study was first time designed to investigate the effect of oxidation on protein digestion and transport properties in boiled sea cucumber body wall (BSCBW) via simulated digestion combine with everted-rat-gut-sac models. Boiling heat treatments led to protein oxidation in SCBW, manifested by increases in free radical intensity, thiobarbituric acid reactive substances, carbonyl groups, disulfide bonds, dityrosine bonds, advanced glycation end products, protein hydrophobicity and aggregation, declines in free sulfhydryl group, and secondary structure transition from α-helix to β-sheet. Boiling for 2 h caused the anti-digestion collagen unfolding, provided the action site for protease, and improved the protein digestion and transport levels. On the contrary, excessive oxidative modification of 4 h-BSCBW resulted in decreased protein digestion and transport levels. From the perspective of texture, digestion and transport properties, boiling for 2 h can obtain sea cucumber products with better edible and digestible properties, which is considered to be a better processing condition.

The oral cavity is the gateway for microorganisms into your body where they disseminate not only to the directly connected respiratory and digestive tracts, but also to the many remote organs. Oral microbiota, traveling to the end of the intestine and circulating our body through blood vessels, not only affect a gut microbiome profile, but also many systemic diseases. By gathering information accumulated from the era of focal infection theory to the age of revolution in microbiome research, we propose a pivotal role of “leaky gum”, as an analogy of “leaky gut”, to underscore the importance of the oral cavity in systemic health. The oral cavity has unique structures, the gingival sulcus (GS) and the junctional epithelium (JE) below the GS, which are rarely found anywhere else in our body. The JE is attached to the tooth enamel and cementum by hemidesmosome (HD), which is structurally weaker than desmosome and is thus vulnerable to microbial infiltration. In the GS, microbial biofilms can build up for life, unlike the biofilms on the skin and intestinal mucosa that fall off by natural process. Thus, we emphasize that the GS and the JE are the weakest leaky point for microbes to invade human body, making the leaky gum just as important as, or even more important than, the leaky gut.

Background: The gut microbiome plays a major role in chronic diseases, of which several are characterized by an altered composition and diversity of bacterial communities. Large-scale sequencing projects allowed characterizing the perturbations of these communities. However, translating these discoveries into clinical applications remains a challenges. To facilitate routine implementation of microbiome profiling in clinical settings, portable, real-time, and low-cost sequencing technologies are needed. Results: Here, we propose a computational and experimental protocol for whole genome quantitative metagenomics studies of human gut microbiome with Oxford Nanopore sequencing technology (ONT) that could be applied to other microbial ecosystems. We developed a bioinformatic protocol to analyse ONT sequences taxonomically and functionally and optimized pre-analytic protocols including stool collection and DNA extraction methods to maximize read length. This is a critical parameter for the sequence alignment and classification. Our protocol was evaluated using simulations of metagenomic communities which reflect naturally occuring compositional variations. Next, we validated both protocols using stool samples from a bariatric surgery cohort, sequenced with ONT, Illumina and SOLiD technologies. Results revealed similar diversity and microbial composition profiles. Conclusion: This protocol can be implemented in the clinical or research setting, bringing rapid personalized whole genome profiling of target microbiome species.

The modification the gut microbiota in metabolic syndrome and associated chronic diseases is among leading tasks of microbiome research and needs for clinical use of probiotics. Evidence lack for the implications for microbiome modification to improve metabolic health in particular when applied impersonalized. Probiotics have tremendous potential in personalized nutrition and medicine to develop healthy diets. The aim was to to conduct comprehensive overview of recent updates of role of microbiota on human health and development of metabolic syndrome and efficacy of microbiota modulation considering specific properties of probiotic strain and particular aspects of metabolic syndrome and patient`s phenotype to fill the gap between probiotic product and individual to facilitate development of individualized / personalized probiotic and prebiotic treatments. We discuss the relevance of using host phenotype-associated biomarkers, those based on imaging and molecular and patrient`s history, reliable and accessible to facilitate person-specific appication of probiotics and prebiotic substances. Microbiome phenotypes can be parameters of predictive medicine to recognize patient`s predispositions and evaluate treatment responses; the number of phenotype markers can be effectively involved to monitor microbiome modulation. The studied strain-dependent properties of probiotic strains are potentially relevant for individualized treatment for gut and distant sites microbiome modulation. The evidence regarding probiotic strains properties can be taken to account via pathophysiology-based approach for most effective individualized treatment via gut, oral and vaginal and other sites microbiome modulation according to phenotype of the patient providing individualized and personalized medical approaches. Preventive potential of probiotics is strong and well-documented. Recommendations for individualized clinical use of probiotics, and for probiotic studies design have been suggested.

This study investigated a novel probiotic-enriched ice cream containing fermented white kidney bean homogenate to explore its potential health benefits. We assessed the viability of various probiotic strains during ice cream production and storage, focusing on their potential to reach the gut, and evaluated the overall antioxidant activity using DPPH, ABTS, FRAP, and TPC assays. The incorporation of fermented white bean homogenate significantly increased antioxidant capacity compared to the control group. Notably, strains like L. rhamnosus GG and L. plantarum 299v demonstrated the most pronounced effects on antioxidant activity, suggesting potential synergistic benefits between probiotics and bioactive compounds in fermented white beans. Although all probiotic strains experienced decreased viability during storage, certain strains, particularly L. plantarum 299v and L. casei DN-114001, showed promising survival rates even after 6 months. These results suggest the potential for developing probiotic ice cream containing viable bacteria capable of reaching the gut and contributing to a healthy gut microbiota. This could potentially improve digestion, reduce inflammation, and boost the immune system. Overall, this study highlights the potential of probiotic-enriched ice cream with fermented white kidney bean homogenate to combine the established benefits of probiotics for gut health with the enjoyment of consuming ice cream.

Health-Related Quality of Life (HRQoL) encompasses the comprehensive evaluation of an indi-vidual's health and well-being across multiple dimensions. Mindfulness, recognized as a scientifi-cally supported strategy for anxiety management, plays a role in enhancing both physical and mental health. The Gut-Brain Axis (GBA) serves as the bidirectional communication link between the gastrointestinal system and the central nervous system. This study aims to explore the associa-tion between Mindfulness and factors influencing the GBA in both healthy individuals and those with Inflammatory Bowel Diseases (IBD). A cross-sectional investigation involved 338 adults, in-cluding 50 IBD patients, utilizing validated Greek scales for Mindfulness (MAAS-15), Mediterra-nean Diet (14-MEDAS), and HRQoL (EQ-5D-5L). The questionnaire gathered demographic, an-thropometric, and lifestyle data. Among healthy participants, EQ-5D-5L showed a moderate cor-relation with the MAAS-15 scale (r=0.389, p

The gut-brain axis (GBA) represents a complex, bidirectional communication network that intri-cately connects the gastrointestinal tract with the central nervous system (CNS). Understanding and intervening in this axis opens a pathway for therapeutic advancements. In light of this, the current review assesses the effectiveness of neuromodulation techniques in treating neurological and gastrointestinal disorders by modulating the GBA, involving key elements such as gut micro-biota, neurotrophic factors, and proinflammatory cytokines. Through a comprehensive literature review encompassing PubMed, Google Scholar, Web of Science, and the Cochrane Library, and analyzing 182 relevant articles, this research highlights how neuromodulation can positively impact the management of functional gastrointestinal disorders (FGIDs), chronic pain, inflammation, and a range of GI disorders like Crohn's disease and ulcerative colitis. Despite existing challenges, the ability of neuromodulation to adjust disrupted neural pathways, alleviate pain, and mitigate in-flammation is significant in improving the quality of life for patients, thereby offering exciting prospects for future advancements in patient care.

: Microplastics and nanoplastics (MNPs) are becoming an increasingly severe global problem due to their widespread distribution and complex impact on living organisms. Apart from their environmental impact, the effects of MNPs on living organisms have also continued to attract attention. The harmful impact of MNPs has been extensively documented in marine invertebrates and larger marine vertebrates like fish. However, the research on the toxicity of these particles on mammals is still limited, and their possible effects on humans are poorly understood. Considering that MNPs are commonly found in food or food packaging, humans are primarily exposed to them through ingestion. It would be valuable to investigate the potential harmful effects of these particles on gut health. This review focuses on recent research exploring the toxicological impacts of micro- and nanoplastics on the gut, as observed in human cell lines and mammalian models. Available data from various studies indicate that the accumulation of MNPs in mammalian models and human cells may result in adverse consequences, in terms of epithelial toxicity, immune toxicity, and disruption of gut microbiota. The paper also discusses the current research limitations and prospects in this field, aiming to provide a scientific basis and reference for further studies on the toxic mechanisms of micro- and nanoplastics.

Gut luminal dysbiosis and pathobiosis result in compositional and biodiversify alterations in the microbial and host co-metabolites. The main mechanism of bacterial evolution is horizontal gene transfer (HGT) and acquisition of new traits can be achieved through mobile genetic element (MGEs) exchange. Introducing genetically engineered microbes (GEMs) might break the harmonized balance in the intestinal compartment. The present objectives are: 1. To reveal the role played by GEMs' horizontal gene transfers in changing the landscape of the enteric microbiome eubiosis 2. To expand on the potential detrimental effects of those changes on human genome and health. A search of articles published in PubMed/MEDLINE, EMBASE, and Scielo from 2000 to august 2023, using appropriate MeSH entry terms were performed. GEMs' horizontal gene exchanges might induce multiple human diseases. The new GEMs can change the long-term natural evolution of the enteric pro- or eukaryotic cells inhabitants. The worldwide regulatory authority's safety control of GEMs is not enough to protect public health. Viability and biocontainment and many other aspects are only partially controlled and harmful consequences for public health should be avoided. Always remember that prevention is the most cost- effective strategy and "primum non nocere" is the name of the game.

An array of diverse processes and factors have been linked to the pathoetiology and pathophysiology of Parkinson’s disease (PD), including systemic CNS factors. This article reviews some of the many processes and factors linked to the emergence and progression of PD that culminates in the loss of substantia nigra pars compacts (SNpc) in PD patients. It is proposed that SNpc astrocytes may be a key hub, with numerous systemic and CNS factors acting to suppress the astrocyte tryptophan-melatonin pathway, leading to a loss of astrocyte melatonin and lactate for SNpc dopamine neurons. Consequently, dopamine neurons show an increase in α-synuclein, oxidative stress and suboptimal mitochondrial function, partly due to the loss of melatonin induced PTEN-associated kinase (PINK)1/parkin and mitophagy. This leads to an increase in the major histocompatibility (MHC)-1 and the chemoattraction of CD8+ T cells that destroy SNpc dopamine neurons in an ‘autoimmune’/’immune-mediated’ manner. The upstream processes driving the end-point ‘chaos’ of SNpc dopamine neuron loss are proposed to be driven by the suppression of night-time pineal melatonin, gut microbiome derived butyrate and possibly bcl2-associated athanogene (BAG)-1, which all act to suppress the glucocorticoid receptor (GR) translocation to the nucleus in all systemic and CNS cells, thereby potentiating the effects of the rising levels of cortisol over the night and accelerated rise in the course of the cortisol awakening response (CAR). The potentiation of cortisol effects at the GR has consequences for the homeostatic regulation of the diverse array of systemic and CNS microenvironments, as well as a distinct regulation of different immune and glia cells. The morning CAR is classically proposed to ‘prepare the body for the coming day’. However, the differential regulation of the GR over the circadian rhythm at night would indicate that such preparation for the coming day may be powerfully determined by night-time factors and processes. The article integrates this systemic, night-time pathoetiology with the ‘immune-mediated’ processes that ultimately drive SNpc dopamine neuron loss. This has a number of novel future research and treatment implications.

Mallard (Anas platyrhynchos) are currently one of the most popular species in rare bird breeding in several southern provinces of China, but there are very few studies on the gut microbial communities of domestic and wild mallards. In this study, 16S rRNA gene high-throughput sequencing technology was used to compare the composition and diversity of gut microbial communities in domestic and wild mallards. Alpha diversity analysis revealed significant differences in the gut microbial communities of domestic and wild mallards. Beta diversity analysis showed that the two groups of stool samples were mostly separated on the principal coordinate analysis (PCOA) plot. In domestic mallards, Firmicutes (67.97%) was the most abundant bacterial phylum, followed by Proteobacteria (24.48%), Bacteroidetes (3.13%), Fusobacteria (2.21%), and Actinobacteria (1.10%). The dominant bacterial phyla in wild mallards were Firmicutes (79.02%), Proteobacteria (12.85%), Fusobacteria (3.37%), and Bacteroidetes (2.79%). At the genus level, a total of 10 dominant genera (Streptococcus, Enterococcus, Clostridium, Lactobacillus, Soilbacillus, Bacillus, Acinetobacter, Comamonas, Shigella, and Cetobacterium) with an average relative abundance greater than 1% were detected in the fecal samples of both groups. The average relative abundance of five potential pathogens (Streptococcus, Enterococcus, Acinetobacter, Comamonas, and Shigella) was higher in domestic mallards than in wild mallards. The enrichment of pathogenic bacteria in the intestinal tract of domestic mallards should be of sufficient concern.

Mallard (Anas platyrhynchos) are currently one of the most popular species in rare bird breeding in several southern provinces of China, but there are very few studies on the gut microbial communities of domestic and wild mallards. In this study, 16S rRNA gene high-throughput sequencing technology was used to compare the composition and diversity of gut microbial communities in domestic and wild mallards. Alpha diversity analysis revealed significant differences in the gut microbial communities of domestic and wild mallards. Beta diversity analysis showed that the two groups of stool samples were mostly separated on the principal coordinate analysis (PCOA) plot. In domestic mallards, Firmicutes (67.97%) was the most abundant bacterial phylum, followed by Proteobacteria (24.48%), Bacteroidetes (3.13%), Fusobacteria (2.21%), and Actinobacteria (1.10%). The dominant bacterial phyla in wild mallards were Firmicutes (79.02%), Proteobacteria (12.85%), Fusobacteria (3.37%), and Bacteroidetes (2.79%). At the genus level, a total of 10 dominant genera (Streptococcus, Enterococcus, Clostridium, Lactobacillus, Soilbacillus, Bacillus, Acinetobacter, Comamonas, Shigella, and Cetobacterium) with an average relative abundance greater than 1% were detected in the fecal samples of both groups. The average relative abundance of five potential pathogens (Streptococcus, Enterococcus, Acinetobacter, Comamonas, and Shigella) was higher in domestic mallards than in wild mallards. The enrichment of pathogenic bacteria in the intestinal tract of domestic mallards should be of sufficient concern.

This study evaluated the anti-inflammatory effects, protection of gut barrier integrity, and stimulation of phagocytosis in peripheral cells of a nutritional supplement based on a synergistic combination of yeast-based ingredients with a unique 1,3/1,6-glucan complex and a consortium of postbiotic Saccharomyces cerevisiae rich in selenium and zinc. The anti-inflammatory effect in Caco-2 cells in the presence and absence of a pro-inflammatory challenge (tumour necrosis factor alpha [TNF-α]/interferon gamma [IFN-ɣ]) showed statistically significant reductions of IFN-ɣ induced protein-10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) levels vs. controls (p &lt; 0.001). Disruption of the gut integrity in the presence or absence of Escherichia coli (ETEC H10407) showed transepithelial electrical resistance (TEER) values higher in the ABB C1® group after 6 hours of testing. Spontaneous build-up of the gut epithelium monolayer over 22 days was also greater in the ABB C1® condition vs. a negative control. ABB C1® showed a significantly higher capacity to stimulate phagocytosis as compared with controls of algae β-1,3-glucan and yeast β-1,3/1,6 glucan (p &lt; 0.001). This study supports the mechanism of action by which ABB C1® may improve the immune response and be useful to prevent infection and allergy in clinical practice.

Probiotics are namely yeast and bacteria which are regarded as dietary supplements and food. Many probiotics are being commonly used now, the most frequently used, lactic acid bacteria are called Lactobacillus and Bifidobacterium. Many of the diseases associated with GIT are related to microbiota found in GIT, an imbalance of which causes gastrointestinal diseases. Probiotics, in light of scientific literature, are thought to play an important role in relieving symptoms of many diseases associated with GIT, i.e. beneficially regulating the microbiota composition. In the present review, we aimed to highlight the main considerations for main probiotic formulations to date. This study reviews the role of different probiotic formulations introduced so far in treating GI diseases in cohort ageing ≤18 years. We searched PubMed and Clinicaltrials.gov without any restrictions. This study comprises the descriptive and comparative analysis between Single-organism and Composite probiotics. These GI diseases include NEC, FAP, AGE, Acute Diarrhea, Ulcerative Colitis and etc. The results have been categorized according to title and outcomes. The positive outcomes emphasize the drug’s effectiveness in improving health and the negative outcome elaborates on the adverse effects the drug may have shown. Conclusively, discussed practices will assist in reducing GI disorders and strengthening the gut. Further insight into the various gut microbes and microbiomes with specific demographic is recommended.

‘Dysbiosis’ of the adult gut microbiota, in response to challenges such as infection, altered diet, stress, and antibiotics treatment has been recently linked to pathological alteration of brain func-tion and behavior. Moreover, gut microbiota composition constantly controls microglia matura-tion as revealed by morphological observations and gene expression analysis. However, it is un-clear whether gut microbiota influences microglia functional properties and crosstalk with neu-rons, known to shape and modulate synaptic development and function. Here, we investigated how antibiotic mediated alteration of the gut microbiota influences microglial and neuronal functions in adult mice hippocampus. Hippocampal microglia from adult mice treated with oral antibiotics exhibited increased microglia density, altered basal patrolling activity, and impaired process rearrangement in response to damage. Patch clamp recordings at CA3-CA1 synapses revealed that antibiotics treatment alters neuronal functions, reducing spontaneous postsynaptic glutamatergic currents and decreasing synaptic connectivity, without reducing dendritic spines density. The effect of dysbiosis on neuronal functions are mediated by microglia-neuron cross-talk through the CX3CL1-CX3CR1 axis, as antibiotics treatment of CX3CR1 deficient mice, mod-ulates microglia density and processes rearrangement leaving unaltered synaptic function. To-gether, our findings show that the antibiotics alteration of gut microbiota impairs synaptic effi-cacy, probably through CX3CL1-CX3CR1 signaling supporting microglia as a major player in in the gut-brain axis, and in particular in the gut microbiota-to-neuron communication pathway.

We have shown that prebiotic xylo-oligosaccharides (XOS) increased beneficial gut microbiota (GM) and prevented high fat diet-induced hepatic steatosis, but the mechanisms behind these effects are not clear. We studied whether XOS affects adipose tissue inflammation and insulin signaling, and whether the GM and fecal metabolome explain associated patterns. XOS was supplemented or not with high (HFD) or low (LFD) fat diet for 12-weeks in male Wistar rats (n = 10/group). Previously analyzed GM and fecal metabolites were biclustered to reduce data dimensionality and identify interpretable groups of co-occurring genera and metabolites. Based on our findings, biclustering provides a useful algorithmic method for capturing such joint signatures. On the HFD, XOS-supplemented rats showed lower number of adipose tissue crown-like structures, increased phosphorylation of AKT in liver and adipose tissue as well as lower expression of hepatic miRNAs. XOS-supplemented rats had more fecal glycine and less hypoxanthine, isovalerate, branched chain amino acids and aromatic amino acids. Several bacterial genera were associated with the metabolic signatures. In conclusion, the beneficial effects of XOS on hepatic steatosis involved decreased adipose tissue inflammation and likely improved insulin signaling, which were further associated with fecal metabolites and GM.

The underlying molecular basis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is not well understood. Characterized by chronic, unexplained fatigue, a disabling payback following exertion (“post-exertional malaise”) and variably presenting, multi-system symptoms, ME/CFS is a complex disease which demands concerted biomedical investigation from disparate fields of expertise. ME/CFS research and patient treatment have been challenged by the lack of diagnostic biomarkers and finding these is a prominent direction of current work. Despite these challenges, modern research demonstrates a tangible biomedical basis for the disorder across many body systems. This evidence is largely comprised of disturbances to immunological and inflammatory pathways, autonomic and neurologic systems, abnormalities in muscle and mitochondrial function, shifts in metabolism, and gut physiology or gut microbiome disturbances. It is possible that these threads are together entangled as parts of an underlying molecular pathology reflecting a far-reaching homeostatic shift affecting each of these systems. Due to the variability of non-overlapping symptom presentation or precipitating events such as infection or other bodily stresses, the initiation of body-wide pathological cascades with similar outcomes stemming from different causes may be implicated in the condition. Patient stratification to account for this heterogeneity is therefore one important consideration during exploration of potential diagnostic developments.

Compelling epidemiologic data support the critical role of dietary fructose in the epidemic of obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). The metabolic effects of fructose on the development of metabolic syndrome and NAFLD are not completely understood. High fructose intake impairs copper status, and copper-fructose interactions have been well documented in rats. Altered copper-fructose metabolism leads to exacerbated experimental metabolic syndrome and NAFLD. A growing body of evidence has demonstrated that copper levels are low in NAFLD patients. Moreover, hepatic and serum copper levels are inversely correlated with the severity of NAFLD. Thus, high fructose consumption and low copper availability are considered two important risk factors in NAFLD. However, the causal effect of copper-fructose interactions as well as the effects of fructose intake on copper status remain to be evaluated in humans. The aim of this review is to summarize the role of copper-fructose interactions in the pathogenesis of the metabolic syndrome and discuss the potential underlying mechanisms. This review will shed light on the role of copper homeostasis and high fructose intake and point to copper-fructose interactions as novel mechanisms in the fructose induced NAFLD.

Abstract: Supplementation of infant formula with ingredients potentially able to manage, in a way positive for the host, the gut microbiota of infants, is nowadays widely used by infant food producers. The impact of this class of compounds, named prebiotics, on gut microbiota composition, was initially measured on the enrichment of Bifidobacterium and Lactobacillus spp., but the use of culture-independent analytical techniques has allowed to establish that a larger number of intestinal microorganisms are affected by the ingestion of prebiotics. However, despite a relevant number of scientific publications, actually there is no consensus on the amount of prebiotics to be administered daily, the potentially different actions exerted by prebiotics which differ in biochemical structures, as well as the impact of different percentages of the same prebiotics when used in mixtures and/or combination. This paper is aimed to critically review the available data on the use of prebiotics in infant formula, with special attention paid to identify a link between, the dosage used, the mixture composition and the observed outcomes, keeping in mind the influences in nutrition quality and growth influence.

There is an important role non-human primates (NHP) play in biomedical research. Phylogenetic proximity of any of the NHP species to Homo sapiens assures that much better translatability of research outcomes from model studies involving human diseases can be achieved than from those generated with other pre-clinical systems. Our group and others used during past two decades NHPs in research directed towards viral and autoimmune disorders of the gastrointestinal tract. This review summarizes progress made in the area of enteric viral infections and its applicability to human disease.

Space exploration is an arduous journey, with future explorations extending in duration, increasing the risk for common space-related health issues such as bone density loss due to microgravity, impaired gut microbiota, cardiovascular ailments, and exposure to cosmic radiation. These ailments can be addressed using medicinal plants. Enhancing their efficacy entails employing gene editing to target specific secondary metabolite pathways associated with therapeutic properties. Moreover, gene editing can combine multiple medicinal properties from various plants, culminating in a singular 'superplant' with enhanced therapeutic benefits. This review discusses the current usage of medicinal plants in promoting human health during space travel, the application of gene editing technology in modifying medicinal plants and presents a vision for the utilization of gene-edited medicinal plants in space to mitigate the risk of various space-related health issues.

Background & Aims: Gut microbial imbalances are linked to colorectal cancer (CRC), but archae-‎a's role remains underexplored. Here, we performed bioinformatic and statistical analysis looking ‎for archaeal taxonomic and functional signatures related to CRC. Methods: We analyzed pub-‎lished fecal metagenomic data from 390 subjects, comparing the archaeomes of CRC and healthy ‎individuals. We conducted a biostatistical analysis to investigate the relationship between Candi-‎datus Mancarchaeum acidiphilum (DPANN superphylum) and other archaeal species associated ‎with CRC. Using the Prokka tool, we annotated the data focusing on archaeal genes, subsequently ‎linking them to CRC and mapping them against UniprotKB and GO databases for specific ar-‎chaeal gene functions. Results: Our analysis identified enrichment of methanogenic archaea in ‎healthy subjects, with an exception for Methanobrevibacter smithii, which correlated with CRC. ‎Notably, CRC showed a strong association with archaeal species, particularly Natrinema sp. J7-2, ‎Ferroglobus placidus, and Candidatus Mancarchaeum acidiphilum. Furthermore, the DPANN ar-‎chaeon exhibited a significant correlation with other CRC-associated archaea (p < 0.001). Func-‎tionally, we found a marked association between MvhB-type polyferredoxin and colorectal can-‎cer. We also highlighted the association of archaeal proteins involved in the biosynthesis of leucine ‎and the galactose metabolism process with the healthy phenotype. Conclusion: The archaeomes ‎of CRC patients show identifiable alterations, including a decline in methanogens and an increase ‎in Halobacteria species. MvhB-type polyferredoxin, linked with CRC and species like Candidatus ‎Mancarchaeum acidiphilum, Natrinema sp. J7-2 and Ferroglobus placidus emerge as potential archaeal ‎biomarkers. Archaeal proteins may also offer gut protection, underscoring archaea’s role in CRC ‎dynamics.

Chronic gastroduodenal symptoms are prevalent worldwide, and there is a need for new diagnostic and treatment approaches. Several overlapping processes may contribute to these symptoms, including gastric dysmotility, hypersensitivity, gut-brain axis disorders, gastric outflow resistance, and duodenal inflammation. Gastric Alimetry® (Alimetry, New Zealand) is a non-invasive test for evaluating gastric function that combines body surface gastric mapping (high-resolution electrophysiology) with validated symptom profiling. Together, these complementary data streams enable important new clinical insights into gastric disorders and their symptom correlations, with emerging therapeutic implications. A comprehensive database has been established, currently comprising >2,000 Gastric Alimetry tests, including both controls and patients with various gastroduodenal disorders. From studies employing this database, this pa-per presents a systematic methodology for Gastric Alimetry test interpretation, together with an extensive supporting literature review. Reporting is grouped into four sections: Test Quality, Spectral Analysis, Symptoms, and Conclusions. This review compiles, assesses, and evaluates each of these aspects of test assessment, with discussion of relevant evidence, example cases, limitations, and areas for future work. The resultant interpretation methodology is recommended for use in clinical practice and research to assist clinicians in their use of Gastric Alimetry as a diagnostic aid, and is expected to continue to evolve with further development.

We set up this preliminary study to evaluate one main question: could strengthening the microbiome have potential benefits for patients suffering with adverse effects after stopping long term topical steroid use? We aim to turn it into a much larger study if the results show promise. After commonly being prescribed for eczema, cessation of topical steroid use, especially after long periods of inappropriate use, can leave lasting adverse effects on the body and skin, known by some as topical steroid withdrawal (TSW). Furthermore, the subsequent withdrawal the body experiences when coming off the drug can leave lasting adverse effects on the body and skin, known by some as topical steroid withdrawal (TSW). This preliminary study involved seven human participants suffering with skin problems associated with TSW who approached Dr. Anja Gijsberts-Veens of their own volition because they were interested in more natural recovery methods. Five completed the study in full. Progress in skin condition was tracked by self-assessed symptom severity questionnaires filled out at the beginning and end of the study. The skin microbiome was addressed by using a 100% natural product shown in previous work to significantly increase skin microbiome biodiversity. Three participants implemented dietary changes and supplementation in response to guidance after fecal sample analysis to improve their gut health and biodiversity. The average improvement in skin symptoms for all participants was 40% and average symptom improvement ranged from 14% for Patient 5 to 92% for Patient 1. On average, the participants saw an improvement in 85% of their symptoms and a stagnation or regression in 11% and 4% respectively. We believe these results show enough promise to warrant expansion of this research to use a larger sample size, preferably 50+ participants, in future work. We also aim to swab the skin of participants to assess the effect on the skin microbiome from skin and gut treatments, as well as including more in-depth analysis of skin and gut microbiomes.

Recent research has identified the gut-brain axis as a key mechanistic pathway and potential therapeutic target in depression. In this paper, the potential role of gut hormones as potential treatments or predictors of response in depression is examined, with specific reference to the peptide hormone motilin. This possibility is explored through two methods: (a) a conceptual review of the possible links between motilin and depression, including evidence from animal and human research as well as clinical trials, and (b) an analysis of the relationship between a functional polymorphism (rs2281820) of the motilin (MLN) gene and cross-national variations in the prevalence of depression. It was observed that (a) there are several plausible mechanisms, including interactions with diet, monoamine, and neuroendocrine pathways, to suggest that motilin may be relevant to the pathophysiology and treatment of depression, and (b) there was a significant correlation between rs2281820 allele frequencies and the prevalence of depression after correcting for multiple confounding factors. These results suggest that further evaluation of the utility of motilin and related gut peptides as markers of antidepressant response is required, and that these molecular pathways represent potential future mechanisms for antidepressant drug development.

Introduction: Despite the introduction of increasingly multifaceted diagnostic techniques and the general progress of emergency abdominal and vascular surgery, the outcome of treatment of patients with acute impaired intestinal circulation remains unsatisfactory. The non-invasive and high-resolution technique of optical coherence tomography (OCT) can be used intraoperatively to assess intestine viability and associated conditions that frequently emerge under conditions of impaired blood circulation. This study aims to demonstrate the effectiveness of multimodal (MM) OCT for intraoperative diagnostics of both the microstructure (cross-polarization OCT mode) and microcirculation (OCT angiography mode) of the small intestine wall in patients with acute mesenteric ischemia (AMI). Methods and Participants: A total of 18 patients were enrolled in the study. Nine of them suffered from AMI in segments II-III of the superior mesenteric artery (AMI group), where the ischemic segments of the intestine were examined. Nine others were operated for adenocarcinoma of the colon (control group), thus allowing areas of their normal small intestine to be examined for comparison. Data on the microstructure and microcirculation in the walls of the small intestine were obtained intraoperatively from the side of the serous membrane using the MM OCT system (IAP RAS, Russia) before bowel resection. The MM OCT data were compared with the results of histological examination. Results: The study finds that MM OCT visualized the damage to serosa, muscularis externa, and blood vessels localized in these layers in 100% of AMI cases. It also visualized the submucosa in 33.3% of AMI cases. The MM OCT image of non-ischemic (control group), viable ischemic and necrotic small intestines (AMI group) differed significantly across stratification of the distinguishable layers, the severity of intermuscular fluid accumulations and the type and density of the vasculature. Conclusion: The MM OCT diagnostic procedure optimally meets the requirements of emergency surgery. Data on the microstructure and microcirculation of the intestinal wall can be obtained simultaneously in real time without requiring contrast agent injections. The depth of visualization of the intestinal wall from the side of the serous membrane is sufficient to assess the volume of the affected tissues. However, the methodology for obtaining MM OCT data needs to be improved to minimize the motion artefacts generated in actual clinical conditions.

Our knowledge on the plastic functions of the serotonin (5-HT) receptor subtype 7 (5-HT7R) in the brain physiology and pathology considerably advanced in the last few years. A wealth of data show that the 5-HT7R is a key player in the establishment and remodeling of neuronal cytoarchitecture during development and in the mature brain, and its dysfunction is linked to neuropsychiatric and neurodevelopmental diseases. The involvement of this receptor in synaptic plasticity is further demonstrated by data showing that its activation allows to rescue long term potentiation (LTP) and long term depression (LTD) deficits in various animal models of neurodevelopmental diseases. In addition, it is becoming clear that the 5-HT7R is involved in inflammatory intestinal diseases, possibly playing a role in the gut-brain axis, and modulates the function of immune cells. In this review, we will mainly focus on recent findings on this receptor’s role in the structural and synaptic plasticity of the mammalian brain, although we will also illustrate novel aspects highlighted in gut and immune system.

Major depressive disorder (MDD) and substance use disorder (SUD) are of immense medical and social concerns. Although significant progress on neuronal involvement in mood and reward circuitries has been achieved, only relatively recently the role of glia in these disorders have attracted attention. Detail understanding of the glial function in these devastating diseases could offer novel interventions. Here, following a brief review of circuitries involved in mood regulation and reward perception, specific contribution of the neurotrophic factors, neuroinflammation and gut microbiota to these diseases are highlighted. In this context, the role of specific glial cells (e.g., microglia, astroglia, oligodendrocytes and synantocytes) on phenotypic manifestation of MDD or SUD are emphasized. In addition, potential use of this knowledge in developing novel therapeutics is touched upon.

Keywords: bariatric surgery, sleeve gastrectomy, Roux-en-y gastric bypass, obesity, microbiota, gut-brain axis, beck scale, depression, diet, probiotics

Background: allergic diseases and, in particular food allergy (FA), have been identified as one of the major diseases in the world. The first 1000 days of life can be a “window of opportunity” or a “window of susceptibility” during which several factors can predispose children to FA development. Changes in gut microbiota composition, from pregnancy to infancy, could have a pivotal role in this regard: some bacterial genus such as Lactobacillus or Bifidobacterium seem to be protective from FA development, on the contrary Clostridium and Staphylococcus appear to be unprotective. Methods: we conducted a research through the most recent literature (2013-2023), using Pubmed and Scopus as databases. We included English original papers, clinical trials, metanalysis and reviews. Case reports, series and letters have been excluded. Results: during pregnancy, maternal diet can play a fundamental role in influencing gut microbiota composition of newborns. After birth, human milk can promote the development of protective microbial species by human milk oligosaccharides (HMOs), that play a prebiotic role. Also complementary feeding can modify gut microbiota composition. Conclusions: the first two years of life are a critical period where several factors, in genetic predisposed children, can increase the risk of FA development.

Mood disorders are among the commonest mental disorders worldwide. Epidemiological and clinical evidence suggests that there are close links between infectious diseases and mood disorders, but the strength and direction of these association remain largely unknown. Theoretical models have attempted to explain this link based on evolutionary or immune-related factors, but these have not been empirically verified. The current study examined cross-sectional and longitudinal associations between the incidence of infectious diseases and mood disorders, while correcting for climate and economic factors, based on data from the Global Burden of Disease Studies, 1990-2019. It was found that major depressive disorder was positively associated with lower respiratory infections, while bipolar disorder was positively associated with upper respiratory infections and negatively associated with enteric and tropical infections, both cross-sectionally and over a period of thirty years. These results suggest that a complex, bidirectional relationship exists between these disorders. This relationship may be mediated through the immune system as well as through the gut-brain and lung-brain axes. Understanding the mechanisms that link these groups of disorders could lead to advances in the prevention and treatment of both.

The enteric nervous system is affected by inflammatory bowel diseases (IBD). Gut microbiota ferment dietary fibers and produce short-chain fatty acids, such as Butyrate, which bind to G protein-coupled receptors, such as GPR41, and contribute to maintaining intestinal health. This work aimed to study the GPR41 in myenteric neurons and analyze the effect of Butyrate in mice submitted to experimental ulcerative colitis. The 2, 4, 6 trinitrobenzene sulfonic acid (TNBS) was injected intrarectally in C57BL/6 mice (Colitis). Sham group received ethanol (vehicle). One group was treated with 100mg/kg of Sodium Butyrate (Butyrate), and the other groups received saline. Animals were euthanized 7 days after colitis induction. Analyzes demonstrated colocalization of GPR41 with neurons immunoreactive (-ir) to nNOS and ChAT-ir, and absence of colocalization of the GPR41 with GFAP-ir glia. Quantitative results demonstrated losses of nNOS-ir, ChAT-ir, and GPR41-ir neurons in Colitis group, and Butyrate treatment attenuated neuronal loss. The number of GFAP-ir glia increased in Colitis group, whereas Butyrate reduced the number of these cells. In addition, morphological alterations observed in Colitis group were attenuated in Butyrate group. The presence of GPR41 in myenteric neurons was identified and the treatment with Butyrate attenuated the damage caused by experimental ulcerative colitis.

HIV-1 is a complicated and perplexing virus. It infects T cells, reverse transcribes its RNA into DNA, utilizes its host DNA machinery to replicate its HIV-DNA, translates the HIV-DNA into proteins, assembles itself for a budding escape from the T cell, and rapidly mutates its conformation. Partially, due to its complexity, there remains no cure for HIV or AIDs. However, recently with the discovery of TALENs, the use of zinc fingers, and most of all the applications of CRISPR-Cas9 technology, has given researchers new hope in finding alternative gene therapies and treatments for diseases. With more focus on CRISPR-Cas9, this new and novel technology uses a guiding RNA, sgRNA, to lead a Cas9 nuclease to its target for deletion or to change that DNA site. CRISPR-Cas9 can delete point mutations and multiple DNA sites. Because CRISPR can alter DNA sequences, several scientists have conducted research into CRISPR, possibly treating more diseases such as cancer, diabetes, and even HIV. HIV-1 drew the focus of a researcher named Dr. Ebina in 2013 when he was the first to design and apply CRISPR-Cas9 to genes found in the binding sites of HIV-1, inhibiting HIV-1 gene expression. Since 2013, several other researchers have blocked HIV replication and infection through CRISPR-Cas9 targeting the receptors of T cells called the CC chemokine receptor 5 or CCR5. HIV-1 binds to the CD4 receptor of T cells, which consists of co-receptors CCR5 and CXCR4. If CCR5 expression can be removed, the HIV virus cannot bind to T-cells, blocking the initial attachment stage, and discontinuing the infection. However, there remain obstacles and issues for the CRISPR deletion of CCR5 for treating HIV-1. The issues include: 1) finding new and safe methods of CRISPR-Cas9 delivery, 2) clearing the latent HIV reservoirs, 3) improving the sgRNA design to avoid off-target mutations or deletions, and 4) effectively analyze the viral escape of HIV from CRISPR-Cas9 modifications. Therefore, the purpose of this review is to discuss possible techniques for removing the obstacles that can lessen the potential of CRISPR to delete CCR5, repressing HIV-1 into long-term remission or a functional cure.

Three different fields intersect in search of an understanding of the point-of-origin of modern-age diseases: 1) D-amino acids and their role under stress conditions; 2) evolutionary origin of the mitochondrion organelle in the eukaryotic cell; and 3) gut microbiota and human healthHere it is first suggested that D-amino acids function as universal signaling agents, after having evolved as prokaryotic communication, part of an organic communication process that governs the basic activities of all the cells and coordinates cell action.Mitochondria (symbiotic prokaryotic organelles), are creative source of D-amino acids as signaling agents in the central nervous system and in the neuroendocrine systems.Amino acids racemases catalyzes the conversion between the L-enantiomers ( protein building blocks) into D-enantiomers (signaling agents).It is suggested that hectic modern life may affect human health by causing stress to the gut microbiota. These affected, gut microbiota then secrete D-amino acids that enter the blood stream, as signaling agents, causing communication errors in the central nervous system, and in the neuroendocrine systems due to excessive quantity of D-amino acids.Treating gut microbiota with inhibitors of amino acids racemases or finding D-amino acid scavengers may be used in developing novel therapeutic strategies for diseases related to the central nervous system and neuroendocrine systems caused by stressed gut microbiota.

About 10% of angiosperms, an estimated 20,000 species, produce latex from ubiquitous isoprene precursors. Latex, an aqueous suspension of rubber particles and other compounds, functions as an antifeedant and herbivory deterrent. Here, I propose that the solubility of latex in neutral to alkaline pH supports the hypothesis that foregut-fermenting herbivores such as ruminants, kangaroos, sloths, insect larvae and tadpoles have evolved to adapt to the ingestion of latex with the evolution of alkaline anterior digestive chamber(s). However, they consequently become susceptible to the action of Bacillus thuringiensis (Bt) -endotoxin and related bioinsecticides which are activated in alkaline environments. By contrast, hindgut-fermenting herbivores such as horses and rabbits have acidic anterior digestive chambers in which latex coagulates and may cause gut blockage, but in which Bt is not activated. The latex-adapted foregut herbivore vs. latex-maladapted hindgut herbivore hypothesis developed in this paper has implications for foregut-fermenting husbanded livestock and zoo animals which may be provided with latex-containing forage that is detrimental to their gut health. Further, ruminants and herbivorous tadpoles with alkaline anterior chambers are at risk for damage by the supposedly “environmentally-friendly” Bt bioinsecticide which is widely disseminated, or engineered into crops which may enter animal feed streams.

The gut plays a key role in drug absorption and metabolism of orally ingested drugs. Additionally, characterization of intestinal disease processes are increasingly gaining more attention as gut health is an important contributor to our overall health. The most recent innovation to study intestinal processes in vitro is the development of gut-on-a-chip (GOC) systems. Compared to conventional in vitro models they offer more translational value, and many different GOC models have been presented over the past years. Here, we reflect on the almost unlimited choices in designing and selecting a GOC for preclinical drug (or food) development research. Four components that largely influence the GOC design are highlighted, namely 1) the biological research questions, 2) chip fabrication and materials, 3) tissue engineering, and 4) the environmental and biochemical cues to add or measure in the GOC. Examples are presented of GOC studies in the two major areas of preclinical intestinal research: 1) intestinal absorption and metabolism to study the oral bioavailability of compounds, and 2) treatment-orientated research for intestinal diseases. The last section of this review presents an outlook on the limitations to overcome in order to accelerate preclinical GOC research.

Mediterranean Diet (MD), rich in minimally processed plant foods and in monounsaturated fats, but low in saturated fats, meat and dairy products, represents one of the most studied diets for cardiovascular health. It has been shown, from both observational and randomized controlled trials, that MD reduces body weight, improves cardiovascular disease surrogates such as waist-to-hip ratio, lipids, and inflammation markers, and even prevents the development of fatal and non-fatal cardiovascular disease, diabetes, obesity, and other diseases. However, it is unclear whether it offers cardiovascular benefits from its individual components or as a whole. Furthermore, limitations in the methodology of studies and meta-analyses have raised some concerns on its potential cardiovascular benefits. MD is also associated with characteristic changes in the intestinal microbiota, mediated through its constituents. These include increased growth of species producing short-chain fatty acids, such as Clostridium leptum and Eubacterium rectale, increased growth of Bifidobacteria, Bacteroides and Faecalibacterium prausnitzii species, and reduced growth of Firmicutes and Blautia species. Such changes are known to be favorably associated with inflammation, oxidative status, and overall metabolic health. This review will focus on the effects of MD on cardiovascular health through its action on gut microbioma.

Different nutraceuticals are often considered by parents of infants and children with abdominal pain and disorders of the gut-brain interaction. Herb extracts and natural compounds have long been used in traditional medicine, but clinical pediatric trials are very limited. This narrative review based on relevant studies identified through Pubmed-Medline literature search updated to October 2023, focused on the effect of nutraceuticals in infantile colic, functional abdominal pain and irritable bowel syndrome in children and adolescents. Significant reduction of colic episodes and crying time was reported in two studies on fennel (seeds oil or tea), in three studies on different multiple herbal extracts (all including fennel), in one study on Mentha piperita, and in at least two double-blind randomized controlled studies on Lactobacillus reuteri DSM 17938 and Bifidobacterium lactis BB-12 (108 CFU/day for at least 21 days) in breast-fed infants. Compared to placebo, in children with functional abdominal pain or irritable bowel syndrome a significant reduction of pain was reported in two studies supplementing peppermint oil capsules or psyllium fibers, in one study on corn fiber cookies or partial hydrolysed guar gum or a specific multiple herbal extract (STW-5) or vitamin D supplementation. To date, there is a moderate certainty of evidence with a weak grade of recommendation for Lactobacillus reuteri DSM 17938 (108 CFU/day) for reducing pain intensity in children with functional abdominal pain and for Lactobacillus rhamnosus GG (1-3 x109 CFU twice daily) for reducing pain frequency and intensity in children with IBS. Further large and well-designed pediatric studies are needed to prove efficacy and safety of different herbal extracts and prolonged use of studied products in infants and children with pain disorders of the gut-brain interaction.

Traumatic spinal cord injury (SCI) elicits an acute inflammatory response which comprises numerous cell populations. It is driven by the immediate response of macro-phages and reactive M1 microglia, which triggers activation of genes responsible for the dysregulated microenvironment within the lesion site and in the spinal cord parenchyma immediately adjacent to the lesion. Recently published data indicate that microglia induces astrocyte activation and determines the fate of astrocytes. Conversely, astrocytes have the potency to trigger microglial activation and control their cellular functions. Here we review current information about the release of diverse signaling molecules (pro-inflammatory vs anti-inflammatory) in individual cell phenotypes (microglia, astrocytes, blood inflammatory cells) in acute and subacute SCI stages, and how they contribute to delayed neuronal death in a the surrounding spinal cord tissue which is spared and functional but reactive. In addition, temporal correlation in progressive degeneration of neurons and astrocytes and their functional interactions after SCI are discussed. Finally, the review highlight the time-dependent transformation of reactive mi-croglia (M1) and astrocytes (A1) into their neuroprotective phenotypes (M2a, M2c and A2) which are crucial for spontaneous post-SCI locomotor recovery. We also provide sug-gestions on how to increase functional outcome after SCI and discuss key therapeutic approaches.

This study investigated the impact of seven-strain probiotic supplementation on the frequency of T helper 17 (Th17) cells, regulatory T (T-reg) cells, Treg/Th17 ratio, and their gene expression in individuals with severe traumatic brain injury (STBI). Probiotics can influence the gut microbiota, modulate the immune response, and prevent or alleviate certain immune diseases. However, it is necessary to clarify whether probiotics can effectively impact Th cells in STBI patient. Despite the great attention to improving the immune system in most diseases, there is currently no accurate mechanism for the use of probiotics in diseases with damage to the head injury, which can be a basis for the use of probiotics. The primary objective of this study is to address this research gap. The present study was a randomized, double-blind, placebo-controlled trial that enrolled 48 STBI patients. They were treated with probiotics or placebo: 4 capsule/day for 14 days. The pre- and post-study evaluation included examining the frequency of Treg, Th17 cells, as well as the expression of associated immunological parameters (Foxp3 and RORγt) and Treg/Th17 ratio in both groups. No significant differences were found between the two groups in terms of subject characteristics (P>0.05). GCS scores at 14 days were significantly higher in the probiotic compared to the placebo group. The probiotic group showed a significant decrease in Th17 cell and RORγt gene expression (P = 0.022 and P< 0.001, respectively), a notable increase in T-reg and FoxP3 gene expression (P= 0.025 and P< 0.001, respectively), and a higher Treg/Th17 ratio compared to the placebo group. Our study provides promising evidence of the beneficial effects of seven-strain probiotic supplementation on Th cells in individuals with STBI.

The brain reciprocally communicates with the rest of the body via neural, endocrine, immune, and other systems. This is crucial for coordinating the complex behavioral and physiological responses needed to cope with the many challenges of life. The Anterior Cingulate Cortex (ACC) is a key brain structure involved in assessing rewards and threats, as well as activating appropriate responses. This is a dynamic process that depends on evolving needs and challenges. Important challenges include illness or injury. These typically involve inflammation and pain, which evoke neuroinflammatory processes in the brain to drive sickness behaviours. In the short term, sickness behaviours are considered adaptive, as they promote convalescence (e.g. low mood; lethargy, fatigue, social withdrawal), and enhanced threat appraisal (e.g. anxiety) to combat increased risk/vulnerability associated with sickness. Chronic inflammation, however, appears to remodel the system to inappropriately activate threat-coping responses, resulting in depressive and/or anxious phenotypes. These mood disorders are particularly pronounced in diseases and disorders associated with gut dysfunction, which feature chronic inflammation and altered ACC function. We propose that chronic inflammation remodels ACC physiology such that it errantly predicts heightened danger based on a mental model (a.k.a ‘schema’) of the world. This evokes chronic activation of threat-coping systems, including endocrine signaling (e.g. adrenaline), and anxiety. Inflammation can be driven by brain systems involving ACC, leading to a feedback-cycle that self-reinforces pathological states. This theory accounts for a wealth of clinical and preclinical data that implicate the ACC in disorders of mood and gastrointestinal function, and reveals a key player in the gut-brain axis that may represent a novel therapeutic target.