Epilepsy is a neurological disorder that affects approximately 1% of the world's population. To diagnose and estimate the occurrence of epilepsy, the analysis of recorded brain activity is performed by a neurologist, which is not only time-consuming and tedious but also occasionally accompanied by human error. Therefore, in recent decades, researchers have aimed to unravel an approach for designing and building an automated method for diagnosing and estimating the occurrence of epilepsy. Accordingly, the present study proposed two new-fangled ways based on brain signals and a convolutional neural network (CNN). Moreover, this research implements a CNN with a sequential three-layer structure. Numerous experiments were performed, and the accuracy of estimating epilepsy using the developed methods was achieved at 95% without feedback and 97% with feedback. The proposed methods were proven to be more accurate than the previous techniques and can be employed as a physician's assistant once entering the field of operation.

Here, we review findings and trends in sleep research in 2020-2021 demonstrating how COVID-19 and sleep disorders can induce the BBB leakage via neuroinflammation, which might contribute to the 'coronasomnia' phenomenon. The new studies suggest that the controlling of sleep hygiene and quality should be incorporated into the rehabilitation of COVID-19 patients. We also discuss perspective strategies for prevention of COVID-19-related BBB disorders. We demonstrate that sleep might be a novel biomarker of the BBB leakage and the analysis of sleep EEG patterns can be a breakthrough non-invasive technology for diagnosis of the COVID-19-caused BBB disruption.

A facilitative transport system exists on the blood brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to brain. But glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter brain in material quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately. Facilitative transport of glutamate and glutamine exist only on the luminal membranes whereas Na+-dependent transport systems for glutamate, glutamine and some other amino acids are present only on the abluminal membrane. The Na+-dependent cotransporters of the abluminal membrane are in a position to actively transport amino acids from the extracellular fluid (ECF) into the endothelial cells of the BBB. These powerful secondary active transporters couple the energy of the Na+-gradient to move glutamate and glutamine into the ECF whereupon glutamate can exit to blood on the luminal facilitative glutamate transporter. Glutamine may also exit brain on a separate facilitative transport system that exists on the luminal membranes or glutamine can be hydrolyzed to glutamate within the BBB thereby releasing ammonia that is freely diffusible. The γ-glutamyl participate cycle participates indirectly by producing oxoproline (pyroglutamate) that stimulates almost all secondary active transporters yet discovered in the abluminal membranes of the BBB.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Mast cells are tissue-resident immune cells distributed in all tissues and strategically located close to blood and lymphatic vessels and nerves. Thanks to the expression of a wide array of receptors, mast cells act as tissue sentinels, able to detect the presence of bacteria and parasites and to respond to different environmental stimuli. Mast cells originate from bone marrow progenitors that enter the circulation and mature in peripheral organs under the influence of microenvironment factors, thus differentiating in heterogeneous tissue-specific subsets. Even though mast cell activation has been traditionally linked to IgE-mediated allergic reactions, a role for these cells in other pathological conditions including tumor progression has recently emerged. However, several aspects of mast cell biology remain to be clarified. The advent of single-cell RNA sequencing platforms has provided the opportunity to understand mast cell origin and differentiation as well as the phenotype and functions within different tissues, including the gut. This review recapitulates how single cell transcriptomic studies provided insight into mast cell development as well as into the functional role of intestinal MC subsets in health and disease.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

A bacterium known as Akkermansia muciniphila (AkkermansiaA. muciniphila) was detected in human feces in 2004. It is defined as a gram-negative, anaerobic, and mucin-degrading microbe belonging to the Verrucomicrobia species. Although the majority of A. muciniphila is found in the human intestinal tract playing a role in the gut microbiome, there are also smaller levels detected in breast milk and oral cavities as well as in the pancreas and appendix.Evidence suggests that having A. muciniphila present in the gut microbiome has positive effects on human health. As a result, A. muciniphila has been shown to have health benefits when taken as a dietary supplementation where it is considered a promising next-generation probiotic. However, the large-scale production of A. muciniphila remains a challenge due to its need for a stable environment. While culturing A. muciniphila in a mucin-based medium is one option, other strategies that use plate-based mediums have also been explored. Currently, both live and pasteurized forms of A. muciniphila are available on the market and shown to have promising outcomes in animal models. Additionally, researchers are investigating various prebiotics to increase the abundance of A. muciniphila in the human gut. This article presents a detailed summary of the phenotypic characteristics of A. muciniphila and its associations with various human health condition illnesses. Finally, the paper explores A. muciniphila's potential as an effective next-generation probiotic.

Previous investigations have illuminated the significant association between the gut microbiome and a broad spectrum of health conditions, including obesity, diabetes, cardiovascular diseases, and psychiatric disorders. Evidence from certain studies suggests that dysbiosis of the gut microbiota may play a role in the etiology of obesity and diabetes. Moreover, it is acknowledged that dietary habits, pharmacological interventions, psychological stress, and other exogenous factors can substantially influence the gut microbial composition. For instance, a diet rich in fiber has been demonstrated to increase the population of beneficial bacteria, whereas the consumption of antibiotics can reduce these advantageous microbial communities. In light of the established correlation between the gut microbiome and various pathologies, strategically altering the gut microbial profile represents an emerging therapeutic approach. This can be accomplished through the administration of probiotics or prebiotics, which aim to refine the gut microbiota and, consequently, mitigate the manifestations of associated diseases. The present manuscript evaluates recent literature on the relationship between gut microbiota and metabolic syndrome published over the past three years and anticipates future directions in this evolving field.

Primary biliary cholangitis (PBC) is a cholestatic liver disease characterized by immune-mediated injury to small bile ducts. Although PBC is an autoimmune disease, the results of traditional immunosuppressive therapy are disappointing. Nearly 40% of PBC patients do not respond to the first-line drug UDCA. Without appropriate intervention, PBC patients would eventually progress to liver cirrhosis and even death. There is an urgent need to develop new therapies. The gut-liver axis emphasizes the interconnection between the gut and the liver, and there is increasing evidence that gut microbiota and bile acids play an important role in cholestatic diseases. Dysbiosis of gut microbiota, imbalance of bile acids, and immune-mediated bile duct injury constitute the triad of pathophysiology in PBC. Understanding the gut microbiota-bile acid network and corresponding immune functions in PBC provides a new perspective for its treatment strategies. Therefore, we summarize the latest advancements in research of gut microbiota and bile acids in PBC and, for the first time, explore the potential of immune factors related to them as novel immunotherapy targets. This article discusses potential therapeutic approaches focusing on regulating gut microbiota, maintaining bile acid homeostasis, their interactions, and related immune factors.

Polyphenols, long-used components of medicinal plants, have drawn great interest in recent years as potential therapeutic agents because of their safety, efficacy, and wide range of biological effects. Approximately 74% of the world's population still uses plant-based medicines, indicating the ongoing significance of phytochemicals for human health. The study emphasizes the growing body of research examining the role of polyphenols in uncovering their anti-adipogenic and anti-obesity properties. Functions of polyphenols including phenylpropanoids, flavonoids, terpenoids, alkaloids, glycosides, and phenolic acids are distinct due to changes in chemical diversity, and structural characteristics. This review methodically investigates the mechanism of how naturally occurring polyphenols mediate obesity and metabolic function. To this end, hormonal control of hunger has the potential to inhibit pro-obesity enzymes such as pancreatic lipase, the promotion of energy expenditure, and the modulation of adipocytokine production. Specifically, polyphenols affect insulin, a hormone that is essential for regulating blood sugar, and they also play a role in part in a complex web of factors that affect the progression of obesity. This review also explores the immunomodulatory properties of polyphenols, providing insight into their ability to improve immune function. The effects of polyphenols on gut health, improving the number of commensal bacteria, cytokine production suppression, and immune cell mediation, including natural killer cells and macrophages. Taken together, continuous studies are required for prudent and precise mechanisms underlying polyphenols' therapeutic potential in obesity and immunomodulation. In the interim, this review emphasizes the holistic approach to health and promotes the consumption of a wide range of foods and drinks high in polyphenols. This review lays the groundwork for future developments, indicating that the components of polyphenols and their derivatives may provide the answer to urgent worldwide health issues. This compilation of the body of knowledge paves the way for future discoveries in the global treatment of pressing health concerns in obesity and metabolic diseases.

Coffee is one of the most widely consumed beverages in the world, with important repercussions on the health of the individual. Dysbiosis in the gut microbiota is implicated in the occurrence of numerous diseases, and knowledge of it has also proven to be of fundamental importance for the development of new therapeutic strategies. In this narrative review, we thoroughly investigated the link between coffee consumption and its effects on the gut microbiota and their consequences on human health. We have selected the most significant articles published on this very interesting link, with the aim of going deeper in the light of the latest evidence more and more about the relationship that links coffee consumption and its repercussions on the composition of the gut microbiota and on human health.

Bacteria in the gut microbiome play an intrinsic part in immune activation, intestinal permeability, enteric reflex, and entero-endocrine signaling. Gut microbiota communicates with the central nervous system (CNS) through the production of bile acids, short-chain fatty acids (SCFAs), glutamate (Glu), γ-aminobutyric acid (GABA), dopamine (DA), norepinephrine (NE), serotonin (5-HT) and histamine. A vast number of signals generated in the gastrointestinal tract (GIT) reaches the brain via afferent fibers of the vagus nerve (VN). Signals from the CNS are returned to entero-epithelial cells (EES) via efferent VN fibers and communicate with 100 to 500 million neurons in the submucosa and myenteric plexus of the gut wall, which is referred to as the enteric nervous system (ENS). Intercommunications between the gut and CNS regulate mood, cognitive behavior, and neuropsychiatric disorders such as autism, depression, and schizophrenia. The modulation, development, and renewal of nerves in the ENS, and changes in the gut microbiome alter the synthesis and degradation of neurotransmitters, which ultimately influence our mental health. The more we decipher the gut microbiome and understand its effect on neurotransmission, the closer we may get to the developing of novel therapeutic and psychobiotic compounds to improve cognitive functions and prevent mental disorders. In this review, the intricate control of entero-endocrine signaling and immune responses that keep the gut microbiome in a balanced state, and the influence that changing gut bacteria have on neuropsychiatric disorders are discussed.

Aquaculture is a fast-emerging food-producing sector in which fishery production plays an im-perative socio-economic role, providing ample resources and tremendous potential worldwide. However, aquatic animals are exposed to the deterioration of the ecological environment and in-fection outbreaks, which represent significant issues nowadays. One of the reasons for these threats is the excessive use of antibiotics and synthetic drugs that have harmful impacts on the aquatic atmosphere. It is not surprising that functional biotic feeds such as probiotics, prebiotics, postbiotics, and synbiotics have been developed as natural alternatives to sustain a healthy microbial envi-ronment in aquaculture. These functional feed additives possess several beneficial characteristics, including gut microbiota modulation, immune response reinforcement, resistance to pathogenic organisms, improved growth performance, and enhanced feed utilization in aquatic animals. Nevertheless, their mechanisms in modulating the immune system and gut microbiota in aquatic animals are largely unclear. This review discusses current research advancements to fill research gaps and promote effective and healthy aquaculture production.

The aim of the study was to investigate the association between maternal dietary iron intake during pregnancy and the gut microbiota characteristics of both the mother and neonate in a well-characterized cohort. A total of 95 mother-neonate dyads were included in our study, with basic information collected through questionnaires. A semi-quantitative Food Frequency Questionnaire (FFQ) was used to assess maternal dietary intake during pregnancy, and maternal dietary iron intake was categorized into <20 mg/d and ≥20 mg/d groups. Fecal samples were collected from the mother in the third trimester and the neonate, allowing for assessment of the community profile and diversity of gut microbiota via 16S rRNA amplicon sequencing. Then, a comparison between different maternal dietary iron intake groups was conducted, adjusting for delivery mode (VD, vaginal delivery; CS, cesarean section) and other potential confounding factors. No significant differences in community profile and diversity were observed for the maternal gut microbiota in different dietary iron intake groups. In neonate fecal samples, the Shannon (P = 0.044) and Simpson (P = 0.010) diversity indices of the gut microbiota were higher in the maternal dietary iron intake ≥20 mg/d group, while Simpson diversity presented the same tendency in vaginal delivery (P = 0.041) after stratification. The relative abundance of the core genus Bifidobacterium showed a significant difference between groups (4.69 [1.19–12.77] vs. 13.98 [3.44–27.28]; P = 0.044). The abundance of Lactobacillus was different in the ≥20 mg/d group under both delivery modes (VD: beta = 2.9, w = 4.13; CS: beta = 2.77, w = 3.8). Our findings suggest that adequate dietary iron intake during pregnancy may promote beneficial bacterial colonization and increase the biodiversity of the neonate gut microbiota.

Capsaicin, a lipophilic, volatile compound, is responsible for the pungent properties of chili peppers. In recent years, a significant increase in investigations into its properties has allowed the production of new formulations and the development of tools with biotechnological, diagnostic, and potential therapeutic applications. In this way, the possible clinical application of such compound is expanding every year. This opinion article aims to provide a synthesis of recent findings regarding the mechanisms by which capsaicin participates in the control of non-communicable diseases such as obesity, diabetes, and dyslipidemia. This opinion review also discusses the recent findings and clinical studies of the use of capsaicin in body weight control.

Cardiovascular disease (CVD), comprising heart and blood vessel disorders, persists as the foremost contributor to global morbidity and mortality. In modern times, the intricate composition of gut microbiota has garnered significant focus, particularly for its varying impact on diverse ailments. Perturbations in gut microbiota and consequent dysbiosis have demonstrated connections with the advancement and origin of CVD, including conditions like atherosclerosis, hypertension, and heart failure. This comprehensive review delves into the pivotal role of gut microbiota in maintaining cardiovascular well-being.

Background: Globally, about 3.5 billion people are affected by intestinal parasitic infections (IPIs). This study aimed to investigate the effects of IPIs on intestinal wall thickness and its potential association with hypertension in different genders. Methods: A total of 108 subjects, including 83 consecutive patients with symptomatic and laboratory-confirmed IPIs (male = 48; female = 35) and 25 healthy controls (male = 10; female = 15), were recruited. B-mode ultrasound grayscale and color images of the duodenum and colon were obtained with and without water contrast. Results: Patients with IPIs had a tendency towards greater duodenal wall thickness (DUOTHICK = 0.88 ± 0.73 cm) compared to controls (0.595 ± 0.089 cm), p = 0.056. Patients with IPIs also had significantly greater ascending colon wall thickness (ASCTHICK = 1.076 ± 0.29 cm) and descending colon wall thickness (DSCTHICK = 1.175 ± 0.366 cm) compared to controls (ASCTHICK = 0.6015 ± 0.1607 cm, DSCTHICK = 0.6223 ± 0.135 cm), p < 0.05. Men over 50 years had greater DSCTHICK (1.25 ± 0.434 cm) than post-menopausal women (0.986 ± 0.389 cm), p < 0.05. DSCTHICK significantly predicted diastolic blood pressure (β = -0.295, p < .05) and blood sodium level (β = -0.300, p < .05). Conclusion: We demonstrated the effects of IPIs on the intestinal microbiome causing intestinal wall cytoskeletal dysfunction, which led to the development of a "leaky gut syndrome."

Nutrigenomics is the study of the interaction of nutrition and genes, focusing on the influence of nutrients on the genome, proteome, and metabolome, and how nutrition affects human health. In the context of nutrigenomics, bioactive components are dietary ingredients that may transmit information from the external environment and alter gene expression in the cell, and hence the overall function of the organism. It is critical to consider food not only as a source of energy and essential nutrients necessary for life and growth, but also as a factor impacting health/disease, biochemical processes, biochemical pathway activation and affecting the diversity of the gut microbiome. Antimicrobial resistance in pathogenic and commensal microorganisms has emerged as a major public health concern due to emerging antimicrobial resistance genes in E. coli isolates from pig, cattle, chicken, and turkey meat, against tetracycline, streptomycin, and sulfonamides. Also, Salmonella spp. and Campylobacter spp. have shown antibiotic resistance at farms and slaughterhouses, and in animal-based food products. A correlation has been proven between a critical nutrient-responsive signaling system and catabolite control of gene expression, and a two-component signaling system that drives antibiotic resistance in E. faecalis, revealing a previously unknown integration between the nutritional status of the cell and intrinsic antibiotic resistance. Moreover, different nutrigenomic approaches can be applied to mitigate possible emergence of antimicrobial resistance against novel antibiotics. However, little progress has been achieved in converting nutrigenomics information into clinical advice, so far.

The gut microbiota plays a crucial role in maintaining host health and has a significant impact on human health and disease. In this study, we investigated the alpha diversity of gut microbiota in COVID-19 patients and analyzed the impact of COVID-19 variants, antibiotic treatment, type 2 diabetes (T2D), and metformin therapy on gut microbiota composition and diversity. We used a culture-based method to analyze the gut microbiota and calculated alpha-diversity using the Shannon H' and Simpson 1/D indices. We collected clinical data, such as length of hospital stay (LoS), C-reactive protein (CRP) levels, and neutrophil-to-lymphocyte ratio (NLR). We found that patients with T2D had significantly lower alpha-diversity than those without T2D. Antibiotic use was associated with a reduction in alpha-diversity, while metformin therapy was associated with an increase. We did not find significant differences in alpha-diversity between the Delta and Omicron groups. Length of hospital stay, CRP levels, and NLR showed weak to moderate correlations with alpha diversity. Our findings suggest that maintaining a diverse gut microbiota may benefit COVID-19 patients with T2D. Interventions aimed at preserving or restoring gut microbiota diversity, such as avoiding unnecessary antibiotic use and promoting metformin therapy, may improve patient outcomes.

The gut microbiome offers numerous advantages to the hosts, through a variety of physiological mechanisms like firming up gut integrity or shaping the intestinal epithelium. Studies showed 2172 species are identified and isolated from human beings, ordered into twelve different phyla, of which 93.5% belonged to Bacteroidetes, Firmicutes, Proteobacteria and Actinobacteria. Out of the 12, three phyla are identified. Human microbial communities are affected by the host external factors like dietary patterns, lifestyle factors, antibiotic usage, internal factors gender, host genotype, age and race. To analyze the dysbiosis and bacterial variation in different areas of District Faisalabad 10,000 individuals of age 25–35 years were recruited from the two different rural and urban localities. The oral swab and fecal sample were collected according to prescribed manner. The collected samples from demographically and geographically distinct regions of District Faisalabad were subjected to DNA extraction and quantification. The amplification of 16s rRNA was carried out by PCR and visualized through a transilluminator. The results revealed significant elevated, % abundance of fecal microbial profile Blautia spp, Firmicutes, Ruminococcaceae, in rural population however non-significant difference % abundance of total Bifido, E. coli, Faecali bacteria, total Lactobacillus were identified in both demographically distinct regions. The pathogenic Gamma Protebacteria, Fusobacterium, Campylobacter coli were not detected in both study areas. Out of five orally detected microbial profiles, elevated % abundance of Firmicutes was detected in rural population however non-significant difference was observed in % abundance of total Bifido and E. coli in both populations. Total Lactobacillus and Fusobacterium were not detected in oral sample of both urban and rural population. Conclusively, this research accomplished the potential effects of demographic and geographical induced dysbiosis in the normal microbiome of the oral cavity and intestine that might cause dysbiosis associated disorders.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Given the growing evidence of gut microbiota being involved in psychiatric (including neurodevelopmental) disorders, we aimed to identify differences in gut microbiota composition between participants with ADHD and controls and to investigate the role of the microbiota in inattention and hyperactivity/impulsivity. Fecal samples were collected from 107 participants (NADHD=42; Ncontrols=50; NsubthreholdADHD=15; range age: 13-29 years). The relative quantification of bacterial taxa was done using 16S ribosomal RNA gene amplicon sequencing. Beta-diversity revealed significant differences in bacterial composition between participants with ADHD and healthy controls, which was also significant for inattention, but showing a trend in case of hyperactivity/impulsivity only. Ten genera showed nominal differences (P < 0.05) between both groups, of which seven genera were tested for their association with ADHD symptom scores (adjusting for age, sex, body mass index, time delay between feces collection and symptoms assessment, medication use and family relatedness). Our results show that variation of a genus from the Ruminococcaceae family (Ruminococcaceae_UCG_004) is associated (after multiple testing correction) with inattention symptoms, and suggest a role of gut microbiota in ADHD pathophysiology.

The composition of bacteria in the gastrointestinal tract of piglets is easily affected by environmental changes, particularly during the weaning period. Compound strains of Lactobacillus reuteri and Lactobacillus salivarius were supplemented to piglets during pre- and post-weaning to determine their effects in improving the growth performance and ameliorating the diarrhea rate and stress caused by antioxidation in piglets. A larger number of L. reuteri and L. salivarius colonized the distal segment of the ileum and the total numbers of Lactobacillus spp. and Bifidobacterium were higher in the ileal mucous membrane and cecal lumen with probiotics supplementation. The numbers of antioxidative and immune molecules were increased in the plasma following compound bacteria (CL) supplementation, whereas cortisol and endotoxin levels were lower and growth hormone and insulin-like growth factor 1 were higher. Spearman’s and KEGG analysis of the bacterial operational taxonomic unit and antioxidative and immune indices and metabolic genes indicated that the body growth modulation by CL supplementation could be attributed to optimization of the intestinal bacterial composition. Collectively, these results suggest that supplementation with CL could reduce stress and improve the growth performance of piglets during weaning by optimizing the intestinal bacterial composition.

The human gastrointestinal tract is inhabited by trillions of commensal bacteria collectively known as the gut microbiota. Our recognition of the significance of the complex interaction between the microbiota, and its host has grown dramatically over the past years. A balanced microbial community is a key regulator of the immune response, and metabolism of dietary components, which in turn, modulates several brain processes impacting mood and behavior. Consequently, it is likely that disruptions within the composition of the microbiota would remotely affect the mental state of the host. Here, we discuss how intestinal bacteria and their metabolites can orchestrate gut-associated neuroimmune mechanisms that influence mood and behavior leading to depression. In particular, we focus on microbiota-triggered gut inflammation and its implications in shifting the tryptophan metabolism towards kynurenine biosynthesis while disrupting the serotonergic signaling. We further investigate the gaps to be bridged in this exciting field of research in order to clarify our understanding of the multifaceted crosstalk in the microbiota-gut-brain interphase, bringing about a novel microbiota-targeted therapeutics for mental illnesses.

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

Introduction: Adverse events related to vaccines are reactions that can lead to serious complications, in the present that we live at the publication of this article with the need to generate high rates of vaccination have been presented in the case of vaccine agents against COVID-19 adverse events, with thrombotic events being the most important. Case Presentation: This is a 37-year-old female patient who presents 11 days after ChAdOx1-S vaccination against COVID-19 presents with intense headache associated with symptoms of intracranial hypertension, she was initially taken to simple cranial tomography showing presence of cerebral edema and indirect signs of cerebral venous thrombosis, it is proposed to carry out cerebral angiography which showed the presence of thrombosis of both transverse venous sinuses, no hypercoagulability states were found in the laboratories, the immunological tests carried out for antiphospholipid syndrome were negative, the thrombotic event was associated with the ChAdOx1-S vaccine, later the patient was taken to thrombectomy by Neuroradiology, achieving complete channeling of both transverse venous sinuses. Conclusions: Adverse events associated with vaccination have been described with multiple vaccine agents, this component against COVID-19 is also an event to consider, knowing the pathophysiology of these events is essential to be able to reduce these risks and select the least risky agent. Despite this risk, vaccination remains the only cost-effective measure to reduce the morbidity and mortality associated with COVID-19.

Brain magnetic resonance imaging (MRI) offers a unique lens to study neuroanatomic support of human neurocognition and intelligence. A core mystery is the MRI explanation of individual differences in neurocognition and intelligence. The past four decades have seen great advancement in studying this century-long mystery, but the sample size and population-level studies limit the explanation at the individual level. The recent rise of big data and artificial intelligence offers novel opportunities. Yet, data sources, harmonization, study design, and interpretation need to be carefully considered. This review aims to summarize past work, discuss rising opportunities and challenges, and facilitate further investigations on machine intelligence inferring human intelligence.

Background: Traumatic brain injury (TBI) remains a significant risk factor for post-traumatic epilepsy (PTE). The pathophysiological mechanisms underlying the injury-induced epileptogenesis are under under investigation. The dentate gyrus, a structure highly susceptible to injury, and has been implicated in the evolution of seizure development. Methods: Utilizing the murine unilateral focal control cortical impact (CCI) injury, we evaluated seizure onset using 24/7 EEG video analysis at 2-4 months post-injury. Cellular changes in the dentate gyrus and hilus of the hippocampus were quantified by non-biased stereology and Imaris image analysis to evaluate Prox1-positive cell migration, astrocyte branching and morphology, as well as neuronal loss at four months post-injury. Isolation of region-specific astrocytes and RNA-seq was performed to determine differential gene expression in PTE+ vs. PTE- that may comport with the epileptogenic process. Results: CCI injury resulted in 37% PTE+-incidence, which increased with injury severity and hippocampal damage. Histological assessments uncovered a significant loss of hilar interneurons that coincided with aberrant migration of Prox1-positive granule cells and reduced astroglial branching in PTE+ compared to PTE- mice. We uniquely identified Cst3 as a PTE+-specific gene signature in astrocytes across all brain regions. Conclusions: These findings suggest that epileptogenesis may emerge following TBI due to distinct aberrant cellular remodeling events and key molecular changes in the dentate gyrus of the hippocampus.

We introduce a mission design for an interstellar expedition to nearby earth-like exoplanets, which our analysis determined to be Tau Ceti and Gliese 667C, at the time of analysis in 2013. We review the research problems in propulsion and AGI that must be addressed to launch an AI guided interstellar probe within 100 years. We propose a new semi-autonomous agent approach for intelligent control of the spacecraft. We introduce the concept of a semi-autonomous agent as having built-in safety guarantees that constrain operation. An autonomous agent case study is presented formulating the objective, constraints, AGI implementation of the agent based on Solomono's Alpha architecture, and adding specicity. We discuss the training required to reach human-level and trans-sapient levels of intelligence which corresponds to an entire crew of AI experts specialized in elds such as astrophysics, astromechanics, astrobiology, quantum physics, computer science, molecular biology, and so forth. We project the feasibility of the human-level AI technology based on empirical ndings in neuroscience, and nd that it should be feasible by 2030. We analyze Solomono's innity point hypothesis in light of Koomey's law about energy eciency of computing and nd that the trends in 2013 indicated an early singularity by 2035, which implies that we might encounter physical bottlenecks which will decelerate computing technology improvements signicantly. We recommend thus year 2040 for launching the probe by which date other required technologies will have been developed. We discuss the scenario of a virtual crew made of brain simulations, which is a bio-information based AI approach. We detail the subsystems of command and control, communication, scientic instrumentation, power, propulsion, navigation, and shielding. We propose a variation of ICAN-II/AIMStar propulsion which uses a positron source instead of anti-protons to initiate micro-fusion reactions. We combine the positron initiated fusion pulse propulsion scheme with a miniaturized version of the Daedelus fusion thruster obtaining high performance. We derive two mission proles one for fusion pulse propulsion, and the yet hypothetical Q-Thruster. Fusion thruster requires 132.2 years for Tau Ceti, and 233.2 years for Gliese 667C, while Q-Thruster takes only 42.3 years for Tau Ceti, and 62.5 years for Gliese 667C. We also discuss extended roles for intelligent interstellar probes such as self-reproduction via nanotechnology, refueling, construction, robotic bodies, and transmission of brain simulations.

There is evidence that spaceflight poses acute and late risks on the central nervous system. To explore possible mechanisms, the proteomic changes following spaceflight in mouse brain were characterized. Space Shuttle Atlantis (STS-135) was launched at the Kennedy Space Center on a 13-day mission. Within 3–5 hours after landing, brain tissue was collected to evaluate protein expression profiles using quantitative proteomic analysis. Our results showed that there were 26 proteins that were significantly altered after spaceflight in the grey and/or white matter. While there was no overlap between the white and grey matter in terms of individual proteins, there was overlap in terms of function, synaptic plasticity, vesical activity, protein/organelle transport, and metabolism. Our data demonstrate that exposure to the spaceflight environment induces significant changes in protein expression related to neuronal structure and metabolic function. This might lead to a significant impact on brain structural and functional integrity that could affect the outcome of space missions.

Traumatic Brain Injury represents a significant public health concern due to its role in traumatic death and disability, often caused by head impacts or rapid accelerations. Despite advancements in Finite Element Head Models, existing models primarily represent adult males, neglecting anatomical and physiological differences between genders and age groups. Additionally, the mechanistic roles of specific intracranial tissues, such as the dura mater, have conventionally been overlooked. To better understand the mechanical behavior of the brain and its injured regions in the context of TBI, including the dura mater, this study proposes the development of a Female Finite Element Head Model. This model, representative of a middle-aged female subject, was developed using medical image-derived geometry and finite element modeling techniques. The validation results demonstrate a similarity between the numerical displacement curves and those obtained experimentally. In the model with dura mater, the numerical results show analogous behavior to the experimental results, despite minimal variations in the amplitude of the curves. These advancements highlight the significance of including the dura mater in biomechanical brain modeling. Incorporating the dura mater in Finite Element Head Models produces more realistic results than models without it. This emphasizes the importance of enhancing biomechanical models to better represent anatomical complexity.

Extracellular vesicles (EVs), including exosomes, microvesicles, and other lipid vesicles derived from cells, play a pivotal role in intercellular communication by transferring information between cells. EVs secreted by progenitor and stem cells have been associated with the therapeutic effects observed in cell-based therapies, and they also contribute to tissue regeneration following injury, such as in orthopedic surgery cases. This review briefly explores the involvement of EVs in tissue repair and nerve regeneration, their potential as drug carriers, and their significance in stem cell research and cell-based therapies. It underscores the importance for bioengineers to comprehend and manipulate EV activity to optimize the efficacy of tissue engineering and regenerative therapies.

The abnormal accumulation of cells in the human brain, if left untreated, may cause brain damage. Management and treatment of these tumours require an early and accurate diagnosis, while their prognostic characterisation can also be beneficial in the choice of care planning for the patient. CDSSs are being continuously developed and integrated into routine clinical practice as they assist clinicians and radiologists to deal with an enormous amount of medical data, reduce clinical errors, and improve diagnostic capabilities. They assist detection, classification, and grading of brain tumours as well as alerting physicians of requirement of change in treatment plans. The aim of this systematic review is to identify various CDSSs used in brain tumour diagnosis and prognosis, that rely on data captured by any imaging modality. Based on the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, the literature search was conducted in PubMed and Engineering Village Compendex databases. This review examines various CDSS tool types, system features, techniques used, accuracy, and outcome, to provide the latest evidence available in the field of neuro-oncology. An overview of different types of CDSSs used to support clinical decision-making in the management and treatment of brain tumours, along with highlighting their benefits, challenges, and future perspectives has been provided.

The appearance of brain metastasis is the most serious complication of breast cancer with mostly fatal outcomes. To reach the brain, tumor cells need to pass the blood-brain barrier (BBB). The molecular mechanisms underlying penetration of the BBB are largely unknown. Previously we found that tumor-infiltrating T lymphocytes enhance the development of brain metastasis of estrogen receptor-negative (ER-) breast cancer. In the current study, we investigate the contribution of T lymphocytes and the IFN- pathway in enabling breast cancer cells to pass the in vitro BBB. CD8+ cells display the strongest stimulatory effect on breast cancer cell passage. We show that inhibition of the IFN- receptor in MDA-MB-231 breast cancer cells, or neutralization of soluble IFN-, impairs the in vitro trespassing of breast cancer cells. Importantly, we validated our findings using gene expression data of breast cancer patients. CXCL-9,-10,-11/CXCR3 axis, dependent on IFN- signaling activity, was overexpressed in primary breast cancer samples of patients who developed brain metastasis. The data support a role for T-lymphocytes and the IFN- pathway in the formation of brain metastasis of ER- breast cancer, and offer targets to design future therapies for preventing breast cancer cells to cross the BBB.

Malignant gliomas are the most common primary brain tumors in adults up to an extent of 78% of all primary malignant brain tumors. However, total surgical resection is almost unachievable due to considerable infiltrative ability of glial cells. The efficacy of current multimodal therapeutic strategies is, furthermore, limited by the lack of specific therapies against malignant cells, and, therefore, the prognosis these in patients is still very unfavorable. The limitation of conventional therapies, which may result from inefficient delivery of the therapeutic or contrast agent to brain tumors are major reasons for this unsolved clinical problem. The major problem in brain drug delivery is the presence of the blood brain barrier which limits the delivery of many chemotherapeutic agents. Nanoparticles, thanks to their chemical configuration, are able to go through the blood-brain barrier carrying drugs or genes targeted against gliomas. Carbon nanomaterials show distinct properties including electronic properties, penetrating capability on the cell membrane, high drug-loading and pH-dependent therapeutic unloading capacities, thermal properties, large surface area and easy modification with molecules, which render them as a suitable candidate to deliver drugs. In this review we will focus on the potential effectiveness of the use of carbon nanomaterials in the treatment of malignant gliomas discussing the current progress of in vitro and in vivo researches of carbon nanomaterials-based drug delivery to brain.

Head injury is among the most devastating types of injury, specifically called Traumatic Brain Injury (TBI). There is need to diminish the morbidity related with TBI and to improve the outcome of patients suffering TBI. Among the improvements on the treatment of TBI, neuroprotection is one of the upcoming improvements. Citicoline has been used in the management of brain ischemia related disorders, such as TBI. Citicoline has biochemical, pharmacological, and pharmacokinetic characteristics that make it a potentially useful neuroprotective drug for the management of TBI. A short review of these characteristics is included in this paper. Also, a narrative review of almost all the published or communicated studies performed with this drug in the management of patients with head injury is included. Based on the results obtained in these clinical studies, it is possible to conclude that citicoline was able to accelerate recovery of consciousness and to improve the outcome of this kind of patients, with an excellent safety profile. Thus, citicoline could have a potential role in the management of TBI.

Current hypotheses implicate insulin resistance of the brain as a pathogenic factor in the development of Alzheimer’s disease and other dementias, Parkinson’s disease, type 2 diabetes, obesity, major depression, and traumatic brain injury. A variety of genetic, developmental, and metabolic abnormalities that lead to disturbances in the insulin receptor signal transduction may underlie insulin resistance. Insulin receptor substrate proteins are generally considered to be the node in the insulin signaling system that is critically involved in the development of insulin insensitivity during metabolic stress, hyperinsulinemia, and inflammation. Emerging evidence suggests that lower activation of the insulin receptor (IR) is another common, while less discussed, mechanism of insulin resistance in the brain. This review aims to discuss causes behind the diminished activation of IR in neurons, with a focus on the functional relationship between mitochondria and IR during early insulin signaling and the related roles of oxidative stress, mitochondrial hypometabolism, and glutamate excitotoxicity in the development of IR insensitivity to insulin.

Current hypotheses implicate insulin resistance of the brain as a pathogenic factor in the development of Alzheimer’s disease and other dementias, Parkinson’s disease, type 2 diabetes, obesity, major depression, and traumatic brain injury. A variety of genetic, developmental, and metabolic abnormalities that lead to disturbances in the insulin receptor signal transduction may underlie insulin resistance. Insulin receptor substrate proteins are generally considered to be the node in the insulin signaling system that is critically involved in the development of insulin insensitivity during metabolic stress, hyperinsulinemia, and inflammation. Emerging evidence suggests that lower activation of the insulin receptor (IR) is another common, while less discussed, mechanism of insulin resistance in the brain. This review aims to discuss causes behind the diminished activation of IR in neurons, with a focus on the functional relationship between mitochondria and IR during early insulin signaling and the related roles of oxidative stress, mitochondrial hypometabolism, and glutamate excitotoxicity in the development of IR insensitivity to insulin.

Human language and social cognition are two key disciplines that have traditionally been studied as separate domains. However, emerging research from detailed studies of comparative animal behavior, human social behavior, language acquisition in children, social cognitive neuroscience, and the cognitive neuroscience of language suggest that language and social cognition are two deeply interrelated capacities of the human species. For instance, recent developmental studies on the acquisition of language in infants and young children, draw attention to the important crucial benefits associated with several different aspects of social stimulation for youngsters, including the quantity and quality of linguistic input, dyadic infant/child-to-parent verbal and non-verbal social interactions, and other important social cues integral for facilitating language learning and social bonding. Studies of the adult human brain further suggest a high degree of specialization for sociolinguistic information processing, memory retrieval, and comprehension, suggesting the function of these regions may link language with social cognition and social bonding. In effect, the social brain and social complexity hypotheses may jointly help to explain how neurotypical children and adults learn language, why autistic adults and children exhibit simultaneous deficits in language and social cognition, and why nonhuman primates and other animals with significant computational abilities do not acquire the capacity for language. But perhaps most critically, the following article argues that this and related research will allow scientists to generate a holistic profile and deeper understanding of the healthy adult social brain, while developing more innovative and effective diagnoses, prognoses, and treatments for maladies and deficits also associated with the social brain.

This review systematically examines the multifaceted relationship between the tumor microenvironment, stromal interactions, and colorectal cancer (CRC) progression and metastasis. The analysis begins by assessing the gut microbiome's influence on CRC development, emphasizing its association with gut-associated lymphoid tissue (GALT). The role of the Wnt signaling pathway in CRC tumor stroma is scrutinized, elucidating its impact on disease progression. Tumor budding, its effect on tumor stroma, and implications for patient prognosis are investigated. The review also identifies conserved oncogenic signatures (COS) within CRC stroma and explores their potential as therapeutic targets. Lastly, the seed and soil hypothesis is employed to contextualize metastasis, accentuating the significance of both tumor cells and the surrounding stroma in metastatic propensity. In summary, this review highlights the intricate interdependence between CRC cells and their microenvironment, providing valuable insights into prospective therapeutic approaches targeting tumor-stroma interactions.

The question of what generates conscious experience has mesmerized thinkers since the dawn of humanity, yet its origins remain a mystery. The topic of consciousness has gained traction in recent years, thanks to the development of large language models that now arguably pass the Turing test, an operational test for intelligence. However, intelligence and consciousness are not related in obvious ways, as anyone who suffers from a bad toothache can attest - pain generates intense feelings and absorbs all our conscious awareness yet nothing particularly intelligent is going on. Still, in the hard sciences, this topic is frequently met with skepticism because to date no protocol to measure the content or intensity of conscious experiences in an observer-independent manner has been agreed upon. Here we present a novel proposal: Conscious experience arises whenever a quantum mechanical superposition forms. Our proposal has several implications: First, it suggests that the structure of the superposition determines the qualia of the experience. Second, quantum entanglement naturally solves the binding problem, ensuring the unity of phenomenal experience. Finally, a moment of agency may coincide with the formation of a superposition state. We outline a research program to experimentally test our conjecture via a sequence of quantum biology experiments. Applying these ideas opens up the possibility of expanding human experience through brain-quantum computer interfaces.

Brain models present a viewpoint on the fundamental structural components of the brain and their mutual organization, generally relative to a particular concept of the brain axis. A model may be based on adult brain structure or on developmental morphogenetic aspects. Brain models usually have functional implications, depending on which functional properties derive from the postulated organization. This essay examines the present scenario about brain models, emphasizing the contrast between columnar or other longitudinal models and transverse subdivisional neuromeric models. In each case, the main functional implications and apparent problems are explored and commented. Particular attention is given to the modern molecularly based ‘prosomeric model’, which postulates a set of 20 transverse prosomeres as the developmental units that serve to construct all the cerebral parts and the particular typology of many different neuronal populations within the forebrain and the hindbrain, plus a number of additional spinal cord units. These metameric developmental units (serially repeated, but with unique molecular profiles) confer to this model remarkable functional properties based mainly on its multiplicity and modularity. Many important brain functions can be decomposed into subfunctions attended to by combined sets of neuronal elements derived from different neuromeres. Each neuromere may participate in multiple functions. Most aspects related to creation of precise order in neural connections (axonal navigation and synaptogenesis) and function is due to the influence of neuromeric anteroposterior and dorsoventral positional information. Research on neuromeric functionality aspects is increasing significantly in recent times.

Light is an electromagnetic radiation that has visible and invisible wavelength spectrum. The visible light can only be detected by the eyes through the optic pathways. With the presence of scalp, cranium and meninges, the brain is seen as being protected from direct exposure to light. For that reason, the brain can be viewed as a black body lying inside a black box. In physics, a black body tends to be in thermal equilibrium with its environment and can tightly regulate its temperature via thermodynamics principles. Therefore, a healthy brain inside a black box should not get exposed to light. On the contrary, photobiomodulation, a form of light therapy to the brain has been shown to have beneficial effects for some neurological conditions. The proposed underlying mechanisms are multiple. Herein we present our intraoperative findings of rapid electrocorticographic brainwave changes when the brain was shone directly with different wavelengths of light during awake brain surgery. Our findings provide literature proof on light’s ability to influence human brain energy and function. Our proposed mechanism for these rapid changes is the presence of plasma-like energy inside the brain which causes fast brain activities that are akin to lightning strikes.

Stereotactic radiosurgery (SRS) has become increasingly important in the management of brain metastases due to improving systemic disease control and rising incidence. Initial trials demonstrated SRS with whole brain radiotherapy (WBRT) improved local control rates versus WBRT alone. Concerns with WBRT associated neurocognitive toxicity have contributed to greater use of SRS alone, including for patients with multiple metastases and following surgical resection. Molecular information, targeted agents and immunotherapy have also altered the landscape for the management of brain metastases. This review summarises current and emerging data on the role of SRS in the management of brain metastases.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Despite impressive progress in quantum biology, many questions about perception, cognition, memory, and their relation to processing of information remain unanswered. Here is an attempt to draw a unified picture starting with the basic quantum-mechanical phenomenon of nano-superconductivity in the microtubules and extending it to quantum processing of information, and generation of coherent Josephson radiation. A model for the generation in the axons of neurons is suggested. Like in a symphony, but on frequencies ten orders of magnitude higher, the radiation forms resonant standing electromagnetic waves, which are defined by the anatomy, synchronize all the functions in organism, and are behind the memory, perception, and cognition of a living being. It is true that we are made of atoms, but we are coherent electromagnetic waves.

Oligodendroglioma (OG) is a brain tumor that contributes to < 1% of brain tumor diagnoses in the pediatric population. Unfortunately, pediatric OG remains without definitive molecular characteristics to aid in diagnosis, and little is known about the tumor microenvironment. Tumor cells' metabolism and proliferation rate are generally higher than healthy cells, so their iron demand is also significantly increased. This consideration underlines the great importance of iron for tumor development and progression. In this context, this study aims to evaluate the effect of iron in a cellular in vitro model of human oligodendroglioma brain tumor. Cell morphology, the effect of siderotic medium on cell growth, iron uptake, and the expression of iron metabolism-related genes were evaluated by optic microscopy, ICP-MS, confocal microscopy, and RealTime PCR, respectively. This study underlines the great importance of iron for tumor development and progression, but also the possibility of reducing the available iron concentration to determine an antiproliferative effect on OGs. Therefore, every attempt can be promising to defeat the OGs for which there are currently no long-term curative therapies.

Brain capillary endothelial cell(s) (BECs) have numerous functions including their semipermeable interface-barrier (transfer and diffusion of solutes), trophic (metabolic homeostasis), tonic (vascular hemodynamics), and trafficking (vascular permeability, coagulation, and leukocyte extravasation) functions to provide brain homeostasis. BECs also serve as the brain’s sentinel cell of the innate immune system and are capable of antigen presentation. In metabolic syndrome (MetS) there are two regions resulting in proinflammatory signaling of BECs. Namely, visceral adipose tissue depots supplying excessive peripheral cytokines/chemokines (pCC) and gut microbiota dysbiotic regions supplying excessive soluble lipopolysaccharide (sLPS), small LPS-enriched extracellular vesicle exosomes (lpsEVexos), and pCC. This dual signaling of BECs at their receptor sites results in BEC activation and dysfunction (BECact/dys) and neuroinflammation. sLPS and lpsEVexos signal BECs toll-like receptor four, which then signals translocated nuclear factor kappa B (NFkB). Translocated NFkB promotes the synthesis and secretion of BEC proinflammatory cytokines and chemokines. Specifically, the chemokine CCL5 (RANTES) is capable of attracting microglia cells to BECs. BEC neuroinflammation activates perivascular space(s) (PVS) resident macrophages. Excessive phagocytosis by reactive resident PVS macrophages results in a stagnation-like obstruction, which along with increased capillary permeability due to BECact/dys could expand the fluid volume within the PVS to result in enlarged PVS (EPVS). Importantly, this remodeling may result in pre- and post-capillary EPVS that would contribute to their identification on T2-weighted MRI, which are considered to be biomarkers for cerebral small vessel disease.

During the 90 days following hospitalization for acute heart failure, ejection fraction and type of discharge medications have been shown in clinical trials to have little effect on mortality. We examined the recent literature addressing brain-related etiologies of sudden death following heart failure. Two mechanisms of sudden unexpected death have been suggested to possibly result from 4 significant influences on pathophysiology in the brain. The two causes of death are severe cardiac arrhythmia, and neurogenic pulmonary edema. They are both mediated through the brainstem autonomic nuclei generally, and executed specifically through the dorsal motor nucleus of the vagus nerve. The four significant influences on pathophysiology in the brainstem autonomic nuclei are: 1) Hyper-stimulation of neurons in the solitary tract nucleus, increasing their metabolic requirements; 2) Inadequate blood flow at a vascular watershed terminus; 3) Additionally decreased blood flow following vasoconstriction related to relative hyperventilation and decreased pCO2 levels; 4) Gravitational ischemia in the brain—caused by the weight of the brain mass sitting above the brainstem. Changes in head tilt release gravitational ischemia in the brain. There is no specific head position (relative to gravity) that is considered favorable or unfavorable for an extended period of time (i.e. more than 24 hours). Even a small degree of head elevation, used in managing pulmonary congestion, may increase gravitational ischemia in the posterior fossa and brainstem. In this paper we suggest a new and important research avenue for intervening in cardiac arrhythmias, and preventing their occurrence, through the non-invasive use of head-tilting, and other head repositioning maneuvers. This could potentially help many geriatric patients with heart failure, who have decreased mobility in bed, and who tend to stay in one position longer, thereby increasing gravitational ischemia in the brain.

Glioblastoma (GBM) is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. GBM shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its distinctive and aggressive features is aberrant angiogenesis, which drives tumor neovascularization, representing a promising candidate for molecular target therapy. Although several pre-clinical studies and clinical trials have shown promising results, anti-angiogenic drugs have not led to a significant improvement in overall survival (OS), suggesting the necessity of identifying novel therapeutic strategies. Metformin, an anti-hyperglycemic drug of the Biguanides family, used as first line treatment in Type 2 Diabetes Mellitus (T2DM), demonstrated in vitro and in vivo antitumoral efficacy in many different tumors, including GBM. From this evidence, a process of repurposing of the drug has begun, leading to the demonstration of the inhibition of various oncopromoter mechanisms and, consequently, to the identification of the molecular pathways involved. Here, we review and discuss the potential metformin’s antitumoral effects on GBM, inspecting if it could properly act as an anti-angiogenic compound to be considered as a safely add-on therapy in the treatment and management of GBM patients.

In recent years, pathoconnectomics emerged as an interesting framework for the investigation and better comprehension of disorders affecting the brain. Research in this field has used so far structural, functional, metabolic and genetic data, but limited attention was addressed to the possible role of vascularization. In the present work the following aspects making it a valuable candidate to pathoconnectomics investigation are discussed: i) The vascular system is by its nature a network, endowed with directionality information on the basis of circulation; ii) The current imaging techniques allow in vivo detection of the vascular system to a good level of detail; iii) The information extracted from this kind of data could interact in a meaningful way with the functional profile of the brain, being the BOLD effect in turn based on blood flow; iv) Further evidence could be found in support of the trophic failure hypothesis; v) Data about vascularization could allow to bring in the pathoconnectomics framework cardiovascular and metabolic disorders. We suggest, therefore, that the evaluation of vascular connectivity (which we propose to name “vesselomics”) could enhance the pathoconnectomics paradigm, and provide new elements towards the understanding of brain pathology.

Since matter, energy and information are the three major components of the world, is there an interaction between information and matter? In the present work, the coevolution of human language and brain is taken as a case of interaction between information and brain. Some evidence that may show interactions between human language and brain revealed by previous researches is summarized in this paper, such as the language areas in the cerebral cortex of the modern human brain, the evolution of human language and brain in human history, and the genetic basis for the evolution of language. Based on the evidence, a dynamic model is developed to investigate the possible mechanism of coevolution of human language and brain. In the model, human language development and brain development reinforce each other: the developmental level of language can be promoted by advances in brain function due to language-related gene mutations, in turn, whether such mutations are selected positively can be influenced by the current developmental level of language. The coevolution of human language and brain can be taken as a case of interaction between information and matter.

Background and objectives: Primary brain tumors include any tumors arising in the brain whose prognosis is poor due to their histologic characteristics. The aim of this research was to evaluate the frequency of HER2 tumor marker in primary malignant brain tumors. Materials and Methods: This descriptive study was conducted on the samples admitted to the pathology laboratory with diagnosis of primary brain tumor during 2008–2015. Results: From among 107 patients (61.7% males and the rest females) with mean age of 40.4 years, the highest frequency of tumor location was in supratentorial region of the brain (including lobes and ventricles) (63.85% cases). High-grade astrocytoma had the highest prevalence at diagnosis (43.9%), followed by low-grade astrocytoma (37.4%). As for HER2 score, 42.1% of patients were HER2-positive (scores 2 & 3). On the other hand, 5.6% of patients were HER2-negative (-), 40.2% were positive (+), and 54.2% were positive (++). The patients with high-grade astrocytoma had older age (P < 0.001), higher HER2 positivity (P = 0.024) and percentage (P < 0.001) compared to the patients with low-grade astrocytoma. Conclusions: HER2 expression is dependent on the type of brain tumors. High expression of HER2 in high-grade astrocytoma may be useful for therapeutic purposes. The future research is needed to confirm these results with a large number of patients in different areas.

Near-infrared spectroscopy (NIRS) has become a key modality in medical imaging, finding application in both brain and breast imaging. This paper discusses the current trends in NIRS for brain and breast imaging, exploring advances in multi-modal integration with modalities such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Challenges related to spatial resolution, depth sensitivity, and the impact of extracerebral tissues on signal specificity are examined. In addition, ongoing efforts to enhance hemodynamic measurements’ quantitative accuracy. Challenges, including limited spatial resolution and tissue heterogeneity, are discussed. The discussion extends to diffuse optical tomography and ongoing instrumentation development, clinical trials and studies validating NIRS diagnostic efficacy in breast imaging. The paper emphasizes the need for standardization, integration into routine clinical practice, and motivates for future work.

There is a growing interest in glial cells in the central nervous system due to their important role in maintaining brain homeostasis both under physiological conditions and after injury. A significant amount of evidence has been accumulated regarding their capacity to exert either pro-inflammatory or anti-inflammatory effects under different pathological conditions. In combination with their known proliferative potential, they contribute not only to the limitation of brain damage and tissue remodeling but also to neuronal repair and synaptic recovery. Moreover, reactive glial cells can modulate the processes of neurogenesis, proliferation, and migration of neurons in the existing neural circuits in the adult brain. By discovering precise signals within specific niches, the regulation of sequential processes in adult neurogenesis holds the potential to unlock strategies that can stimulate the generation of functional neurons, whether in response to injury or as a means of addressing degenerative neurological conditions. Cerebral ischemic stroke, a condition falling within the realm of acute vascular disorders affecting the circulation of the brain, stands as a prominent global cause of disability and mortality. Extensive investigations into glial plasticity and their intricate interactions with other cells in the central nervous system have predominantly relied on studies conducted on experimental animals, including rodents and primates. However, valuable insights have also been gleaned from in vivo studies involving post-stroke patients, utilizing highly specialized imaging techniques. Following the attempts to map brain cells, the role of various transcription factors in modulating gene expression in response to cerebral ischemia is gaining increasing popularity. Although the results obtained thus far remain incomplete and occasionally ambiguous, they serve as a solid foundation for the development of strategies aimed at influencing the recovery process after ischemic brain injury.

The study of the human psyche has elucidated a bipartite structure of logic reflecting the quantum--classical nature of the world. Accordingly, we posited an approach toward studying the brain by means of the quantum--classical dynamics of a mixed Weyl symbol. The mixed Weyl symbol can be used to describe brain processes at the microscopic level and, when averaged over an appropriate ensemble, can provide a link to the results of measurements made at the meso and macro scale. Within this approach, quantum variables (such as, for example, nuclear and electron spins, dipole momenta of particles or molecules, tunneling degrees of freedom, and so on) can be represented by spinors, whereas the electromagnetic fields and phonon modes can be treated either classically or semi-classically in phase space by also considering quantum zero-point fluctuations. Quantum zero-point effects can be incorporated into numerical simulations by controlling the temperature of each field mode via coupling to a dedicated Nos\'e-Hoover chain thermostat. The temperature of each thermostat was chosen in order to reproduce quantum statistics in the canonical ensemble. In this first paper, we introduce a general quantum--classical Hamiltonian model that can be tailored to study physical processes at the interface between the quantum and the classical world in the brain. While the approach is discussed in detail, numerical calculations are not reported in the present paper, but they are planned for future work. Our theory of brain dynamics subsumes some compatible aspects of three well-known quantum approaches to brain dynamics, namely the electromagnetic field theory approach, the orchestrated objective reduction theory, and the dissipative quantum model of the brain. All three models are reviewed.

The advancement of the pediatric traumatic brain injury (TBI) knowledge base requires biospecimens and data from large samples. This study seeks to describe a novel clinical research modality to establish best practices for enrolling a diverse pediatric TBI population and quantifying key information on enrollment into biobanks. Screening form responses were standardized and cleaned through Google Sheets. Data was used to analyze total individuals at each enrollment stage. R was utilized for final analysis, including chi-square goodness of fit and proportion statistical tests, to determine further significance and relationships. Issues throughout data cleaning shed light on limitations of the consent modality. Results suggest that through a diverse research team, the recruited sample exceeds traditional measures of representation (e.g. sex, race, ethnicity). Sex demographics of the study are representative of the local population. Screening for candidates is critical to the success of the consent modality. The consent modality may be modified to increase diversity of study population and accept bilingual candidates. Researchers must implement best practices, including increasing inclusivity of bilingual populations, utilizing technology, and improving participant follow-up, to improve health disparities for understudied clinical populations.

Machine Learning (ML) approaches have been fruitfully applied to several classification problems of neurophysiological activity. Considering the relevance of emotion in human cognition and behaviour, ML found an important application field in emotion identification based on neurophysiological activity. Nonetheless, the literature results present a high variability depending on the neuronal activity measurement, the signal features and the classifier type. The present work aims to provide new methodological insight on ML applied to emotion identification based on electrophysiological brain activity. For this reason, we recorded EEG activity while emotional stimuli, high and low arousal (auditory and visual) were provided to a group of healthy participants. Our target signal to classify was the pre-stimulus onset brain activity. Classification performance of three different classifiers (LDA, SVM and kNN) was compared using both spectral and temporal features. Furthermore, we also contrasted the classifiers performance with static and dynamic (time evolving) features. The results show a clear increased in classification accuracy with temporal dynamic features. In particular, the SVM classifiers with temporal features showed the best accuracy (63.8 %) in classifying high vs. low arousal auditory stimuli.

The basal ganglia (BG) are a central component of the brain, crucial to the initiation, execution and learning of adaptive actions. The BG are the major site of the action of dopamine. An important aspect of the BG architecture is the existence of two paths, direct and indirect, having different projection targets and dopamine receptor expression. To understand the BG, dopamine, and related disorders, it is imperative to understand the two paths. The standard account used in neuroscience research for decades posits that the role of the direct path is to support movements, while that of the indirect path is to suppress unselected or completed movements. This account is contradicted by converging evidence. Here, we explain why the arguments supporting the standard account are flawed, and present a new account, in which the role of the indirect path is completely opposite: to support automated execution. During acute events, the direct path allows coarse responses. These are refined by competition, and the resulting focused response is executed and learned by the indirect path, assisted by cholinergic interneurons and the subthalamic nucleus (STN). The new account allows a novel understanding of the symptoms of Parkinson's disease, in particular tremor and rigidity, and of its treatment by STN deep brain stimulation.

The paper presents a study of two novel visual motion onset stimulus-based brain–computer interfaces (vmoBCI). Two settings are compared with afferent and efferent to a computer screen center motion patterns. Online vmoBCI experiments are conducted in an oddball event–related potential (ERP) paradigm allowing for “aha–responses” decoding in EEG brainwaves. A subsequent stepwise linear discriminant analysis classification (swLDA) classification accuracy comparison is discussed based on two inter–stimulus–interval (ISI) settings of 700 and 150 ms in two online vmoBCI applications with six and eight command settings. A research hypothesis of classification accuracy non–significant differences with various ISIs is confirmed based on the two settings of 700 ms and 150 ms, as well as with various numbers of ERP response averaging scenarios.The efferent in respect to display center visual motion patterns allowed for a faster interfacing and thus they are recommended as more suitable for the no–eye–movements requiring visual BCIs.

A chronic activated pro-inflammatory cytokine network (“inflamm-aging”) may amplify the neurodegenerative effects of a fall induced brain trauma in geriatric subjects. Our research aimed to evaluate how a trained machine learning algorithm may predict recent antecedent falls based only on specific serologic cytokines network analysis and how the consequences of these falls can be substantiated on standard head MRIs. All 279 subjects included in our study were selected from the ADNI1 dataset and all had a mild cognitive impairment diagnostic at the ADNI1 study baseline. A “train group” was built and included 14 subjects with a history of a recent, simple, standing-level fall. These were carefully matched with 14 similar subjects without any antecedent trauma. The “test group” included 251 subjects, all without any history of recent fall. The machine learning algorithm (classic C4.5 decision tree) was trained to detect a pattern of variation in 23 clinically relevant cytokines in relation with an antecedent fall. Changes in five cytokines (matrix metalloproteinase-7, eotaxin-1, interleukin-3, interleukin-8 and matrix metalloproteinase-9) were used for fall prediction in the “test” group. Once trained, the algorithm predicted a recent fall in 119 cases from the test group. The mean brain ventricular volume that was significantly different between fall/non-fall subgroups (41645.5±10337.2 vs 27127.3±6749.4 mm3, p=0.005) remained significant in the test group, after prediction between (41544.24±17343.4 vs 34553.5±10543.2 mm3, p=0.042). The hippocampus mean volume was also significantly different between in the test group (6297.3±1080.1 vs 6745.9±1123.7, p=0.0015). A significant brain ventricular difference was observed in the “65<y.o.” subgroup (p=0.04). If confirmed by larger prospective studies, our findings may increase the precision of the neuro-cognitive assessments in geriatric subjects.

Background: The vegetative state (VS)/unresponsive wakefulness syndrome (UWS) denotes brain-injured, awake patients who are seemingly without awareness. Still, up to 15% of these patients show signs of covert consciousness when examined by functional magnetic resonance imaging (fMRI) or EEG, which is known as cognitive motor dissociation (CMD). Most experts prefer the term unresponsive wakefulness syndrome to avoid the negative connotations associated with vegetative state and to highlight the possibility for CMD. However, the perception of VS/UWS by the public has never been studied systematically. Methods: Using an online crowdsourcing platform, we recruited 1297 participants from 32 countries. We investigated if vegetative state and unresponsive wakefulness syndrome might have a different influence on attitudes towards VS/UWS and CMD. Results: Participants randomized to be inquired about the vegetative state believed that CMD was less common (mean estimated frequency in unresponsive patients 38.07% ± SD 25.15) than participants randomized to unresponsive wakefulness syndrome (42.29% ± SD 26.63; p=0.016). Attitudes towards treatment withdrawal were similar. Most participants preferred unresponsive wakefulness syndrome (60.05%), although a sizeable minority favored vegetative state (24.21%; difference 35.84%, 95% CI 29.36 to 41.87; p<0.0001). Searches on PubMed and Google Trends revealed that unresponsive wakefulness syndrome is increasingly used by academics but not lay people.Discussion: Simply replacing vegetative state with unresponsive wakefulness syndrome may not be fully appropriate given that 1 of 4 prefer the first term. We suggest that physicians take advantage of the controversy around the terminology to explain relatives the concept of CMD and its ethical implications.

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

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

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

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

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

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

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