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Metabolomics has come to the fore as an efficient tool in the search for biomarkers that are critical for precision health approaches and improved diagnostics. This review will outline recent advances in biomarker discovery based on metabolomics, focusing on metabolomics biomarkers reported in cancer, neurodegenerative disorders, cardiovascular diseases, and metabolic health. In cancer, metabolomics provides evidence for unique oncometabolites that are important for early disease detection and monitoring of treatment responses. Metabolite profiling for conditions such as neurodegenerative and mental health disorders can offer early diagnosis and mechanisms into the disease especially in Alzheimer's and Parkinson's diseases. In addition to these, lipid biomarkers and other metabolites relating to cardiovascular and metabolic disorders are promising for patient stratification and personalized treatment. The gut microbiome and environmental exposure also feature among the influential factors in biomarker discovery because they sculpt individual metabolic profiles, impacting overall health. Further, we discuss technological advances in metabolomics, current clinical applications, and the challenges faced by metabolomics biomarker validation toward precision medicine. Finally, this review discusses future opportunities regarding the integration of metabolomics into routine healthcare to enable preventive and personalized approaches. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition that persists into adulthood in the majority of individuals. While the gut-microbiome seems to be relevant for ADHD, the few publications on gut-microbial alterations in ADHD are inconsistent, in the investigated phenotypes, sequencing method/region, preprocessing, statistical approaches, and findings. To identify gut-microbiome alterations in adult ADHD, robust across studies and statistical approaches, we harmonized bioinformatic pipelines and analyses of raw 16S rRNA sequencing data from four adult ADHD case-control studies (N ADHD =312, N NoADHD =305). We investigated diversity and differential abundance of selected genera (logistic regression and ANOVA-like Differential Expression tool), corrected for age and sex, and meta-analyzed the study results. Converging results were investigated for association with hyperactive/impulsive and inattentive symptoms across all participants. Beta diversity was associated with ADHD diagnosis but showed significant heterogeneity between cohorts, despite harmonized analyses. Several genera were robustly associated with adult ADHD; e.g., Ruminococcus_torques_group (LogOdds=0.17, p fdr =4.42 × 10–2), which was more abundant in adults with ADHD, and Eubacterium_xylanophilum_group (LogOdds= -0.12, p fdr =6.9 × 10–3), which was less abundant in ADHD. Ruminococcus_torques_group was further associated with hyperactivity/impulsivity symptoms and Eisenbergiella with inattention and hyperactivity/impulsivity (p fdr <0.05). The literature points towards a role of these genera in inflammatory processes. Irreproducible results in the field of gut-microbiota research, due to between study heterogeneity and small sample sizes, stress the need for meta-analytic approaches and large sample sizes. While we robustly identified genera associated with adult ADHD, that might overall be considered beneficial or risk-conferring, functional studies are needed to shed light on these properties. [ABSTRACT FROM AUTHOR]

Background: Several randomized controlled trials (RCTs) have shown conflicting results on cortisol levels following probiotic administration in healthy and diseased populations. Previous analyses were inconclusive due to limited studies, and evidence is lacking on how these effects vary by health status; region; therapy duration; medications, and use of single or multiple strains. Methods: In this systematic review and meta-analysis (PROSPERO [CRD42024538539]), we searched PubMed, Cochrane Library, Embase, Scopus, Web of Science, CINAHL, ProQuest, and Web of Science Preprints until 13 August 2024, for RCTs on probiotic administration, either alone or combined, across all age groups and without specific medical condition requirements. We applied random-effects meta-analysis, assessed bias using the Cochrane RoB 2 tool, and evaluated evidence certainty with GRADE. Findings: We screened 1739 records and retrieved 46 RCTs (3516 participants). Probiotics supplementation decreased cortisol levels compared to the control arm [46 RCTs; SMD: −0.45; 95% CI: −0.83; −0.07; I2: 92.5%, low certainty]. Among various subgroups; probiotics supplementation decreased the cortisol levels in the subgroups without concomitant medications [37 RCTs; SMD: −0.30; 95% CI [−0.58; −0.03], I2: 88.7%] with a single probiotic strain [30 RCTs; SMD: −0.33; 95% CI: −0.63; −0.028; I2: 88.8%], in a healthy population [35 RCTs; SMD:−0.3; 95% CI: −0.58; −0.03; I2: 88.7] and in the Asia region [21 RCTs; SMD: −0.83; 95% CI: −1.58; −0.07; I2: 95%]. Interpretation: A low level of evidence suggests probiotics might reduce cortisol levels, but more targeted studies are needed to identify variables affecting the response in specific subgroups. [ABSTRACT FROM AUTHOR]

Background: Heat stress (HS) commonly occurs as a severe pathological response when the body's sensible temperature exceeds its thermoregulatory capacity, leading to the development of chronic brain inflammation, known as neuroinflammation. Emerging evidence suggests that HS leads to the disruption of the gut microbiota, whereas abnormalities in the gut microbiota have been demonstrated to affect neuroinflammation. However, the mechanisms underlying the effects of HS on neuroinflammation are poorly studied. Meanwhile, effective interventions have been unclear. β‐Hydroxybutyric acid (BHBA) has been found to have neuroprotective and anti‐inflammatory properties in previous studies. This study aims to explore the modulatory effects of BHBA on neuroinflammation induced by HS and elucidate the underlying molecular mechanisms. Methods: An in vivo and in vitro model of HS was constructed under the precondition of BHBA pretreatment. The modulatory effects of BHBA on HS‐induced neuroinflammation were explored and the underlying molecular mechanisms were elucidated by flow cytometry, WB, qPCR, immunofluorescence staining, DCFH‐DA fluorescent probe assay, and 16S rRNA gene sequencing of colonic contents. Results: Heat stress was found to cause gut microbiota disruption in HS mouse models, and TM7 and [Previotella] spp. may be the best potential biomarkers for assessing the occurrence of HS. Fecal microbiota transplantation associated with BHBA effectively reversed the disruption of gut microbiota in HS mice. Moreover, BHBA may inhibit microglia hyperactivation, suppress neuroinflammation (TNF‐α, IL‐1β, and IL‐6), and reduce the expression of cortical endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP) mainly through its modulatory effects on the gut microbiota (TM7, Lactobacillus spp., Ruminalococcus spp., and Prevotella spp.). In vitro experiments revealed that BHBA (1 mM) raised the expression of the ERS marker GRP78, enhanced cellular activity, and increased the generation of reactive oxygen species (ROS) and anti‐inflammatory cytokines (IL‐10), while also inhibiting HS‐induced apoptosis, ROS production, and excessive release of inflammatory cytokines (TNF‐α and IL‐1β) in mouse BV2 cells. Conclusion: β‐Hydroxybutyric acid may be an effective agent for preventing neuroinflammation in HS mice, possibly due to its ability to inhibit ERS and subsequent microglia neuroinflammation via the gut–brain axis. These findings lay the groundwork for future research and development of BHBA as a preventive drug for HS and provide fresh insights into techniques for treating neurological illnesses by modifying the gut microbiota. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) involves a florid set of clinical manifestations whose autoreactive origin is characterized by an overactivation of the immune system and the production of a large number of autoantibodies. Because it is a complex pathology with an inflammatory component, its pathogenesis is not yet fully understood, assuming both genetic and environmental predisposing factors. Currently, it is known that the role of the human microbiome is crucial in maintaining the transkingdom balance between commensal microorganisms and the immune system. In the present work we study the intestinal microbiota of Argentine patients with different stages of SLE receiving or not different treatments. Microbiota composition and fecal miRNAs were assessed by 16 S sequencing and qPCR. hsa-miR-223–3p, a miRNA involved in several inflammation regulation pathways, was found underexpressed in SLE patients without immunosuppressive treatment. In terms of microbiota there were clear differences in population structure (Weighted and Unweighted Unifrac distances, p-value <0.05) and core microbiome between cases and controls. In addition, Collinsella, Bifidobacterium, Streptococcus genera and aromatics degradation metabolisms were overrepresented in the SLE group. Medical treatment was also determinant as several microbial metabolic pathways were influenced by immunosuppressive therapy. Particularly, allantoin degradation metabolism was differentially expressed in the group of patients receiving immunosuppressants. Finally, we performed a logistic regression model (LASSO: least absolute shrinkage and selection operator) considering the expression levels of the fecal hsa-miR223–3p; the core microbiota; the differentially abundant bacterial taxa and the differentially abundant metabolic pathways (p<0.05). The model predicted that SLE patients could be associated with greater relative abundance of the formaldehyde oxidation pathway (RUMP_PWY). On the contrary, the preponderance of the ketodeoxyoctonate (Kdo) biosynthesis and activation route (PWY_1269) and the genera Lachnospiraceae_UCG_004, Lachnospira, Victivallis and UCG_003 (genus belonging to the family Oscillospiraceae of the class Clostridia) were associated with a control phenotype. Overall, the present work could contribute to the development of integral diagnostic tools for the comprehensive phenotyping of patients with SLE. In this sense, studying the commensal microbial profile and possible pathobionts associated with SLE in our population proposes more effective and precise strategies to explore possible treatments based on the microbiota of SLE patients. • Fecal hsa-miR-223–3p, was found underexpressed in SLE patients without immunosuppressive treatment in the Argentine population. • Medical treatment was also determinant as several microbial genera and metabolic pathways were influenced by immunosuppressive therapy. • A logistic regression model (LASSO) considering the expression levels of fecal hsa-miR223–3p; the core microbiota; differentially abundant bacterial taxa and differentially abundant metabolic pathways (p<0.05), could contribute to the development of integral diagnostic tools for the comprehensive phenotyping of patients with SLE. [ABSTRACT FROM AUTHOR]

Abstract With new advances in next generation sequencing (NGS) technology at reduced costs, research on bacterial genomes in the environment has become affordable. Compared to traditional methods, NGS provides high-throughput sequencing reads and the ability to identify many species in the microbiome that were previously unknown. Numerous bioinformatics tools and algorithms have been developed to conduct such analyses. However, in order to obtain biologically meaningful results, the researcher must select the proper tools and combine them to construct an efficient pipeline. This complex procedure may include tens of tools, each of which require correct parameter settings. Furthermore, an NGS data analysis involves multiple series of command-line tools and requires extensive computational resources, which imposes a high barrier for biologists and clinicians to conduct NGS analysis and even interpret their own data. Therefore, we established a public gut microbiome database, which we call Twnbiome, created using healthy subjects from Taiwan, with the goal of enabling microbiota research for the Taiwanese population. Twnbiome provides users with a baseline gut microbiome panel from a healthy Taiwanese cohort, which can be utilized as a reference for conducting case-control studies for a variety of diseases. It is an interactive, informative, and user-friendly database. Twnbiome additionally offers an analysis pipeline, where users can upload their data and download analyzed results. Twnbiome offers an online database which non-bioinformatics users such as clinicians and doctors can not only utilize to access a control set of data, but also analyze raw data with a few easy clicks. All results are customizable with ready-made plots and easily downloadable tables. Database URL: http://twnbiome.cgm.ntu.edu.tw/ .

Metastatic disease, a leading and lethal indication of deaths associated with tumors, results from the dissemination of metastatic tumor cells from the site of primary origin to a distant organ. Dispersion of metastatic cells during the development of tumors at distant organs leads to failure to comply with conventional treatments, ultimately instigating abrupt tissue homeostasis and organ failure. Increasing evidence indicates that the tumor microenvironment (TME) is a crucial factor in cancer progression and the process of metastatic tumor development at secondary sites. TME comprises several factors contributing to the initiation and progression of the metastatic cascade. Among these, various cell types in TME, such as mesenchymal stem cells (MSCs), lymphatic endothelial cells (LECs), cancer-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs), T cells, and tumor-associated macrophages (TAMs), are significant players participating in cancer metastasis. Besides, various other factors, such as extracellular matrix (ECM), gut microbiota, circadian rhythm, and hypoxia, also shape the TME and impact the metastatic cascade. A thorough understanding of the functions of TME components in tumor progression and metastasis is necessary to discover new therapeutic strategies targeting the metastatic tumor cells and TME. Therefore, we reviewed these pivotal TME components and highlighted the background knowledge on how these cell types and disrupted components of TME influence the metastatic cascade and establish the premetastatic niche. This review will help researchers identify these altered components' molecular patterns and design an optimized, targeted therapy to treat solid tumors and restrict metastatic cascade. [ABSTRACT FROM AUTHOR]

To improve performance and recovery faster, athletes are advised to eat more often than usual and consume higher doses of simple carbohydrates, during and after exercise. Sports energetic supplements contain food additives, such as artificial sweeteners, emulsifiers, acidity regulators, preservatives, and salts, which could be harmful to the gut microbiota and impair the intestinal barrier function. The intestinal barrier plays a critical function in bidirectionally regulation of the selective transfer of nutrients, water, and electrolytes, while preventing at the same time, the entrance of harmful substances (selective permeability). The gut microbiota helps to the host to regulate intestinal homeostasis through metabolic, protective, and immune functions. Globally, the gut health is essential to maintain systemic homeostasis in athletes, and to ensure proper digestion, metabolization, and substrate absorption. Gastrointestinal complaints are an important cause of underperformance and dropout during endurance events. These complications are directly related to the loss of gut equilibrium, mainly linked to microbiota dysbiosis and leaky gut. In summary, athletes must be cautious with the elevated intake of ultra-processed foods and specifically those contained on sports nutrition supplements. This review points out the specific nutritional interventions that should be implemented and/or discontinued depending on individual gut functionality. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by accelerated platelet clearance. Gut dysbiosis was associated with its pathogenesis, but the underlying mechanisms have not been fully elucidated. Patients with ITP exhibit varying degrees of responsiveness to corticosteroid treatment. Therefore, prognostic indexes for corticosteroid responsiveness in ITP could offer valuable guidance for clinical practices. The present study examined the signature of six types of gut-microbiota metabolites and forty-eight types of cytokines, chemokines, and growth factors and their clinical significance in patients with ITP. Both patients with good and poor corticosteroid responsiveness exhibited significantly elevated/suppressed secretion of twenty-two cyto(chemo)kins/growth factors in comparison to healthy controls. Additionally, patients with ITP demonstrated a significant decrease in plasma levels of trimethylamine-N-oxide (TMAO), which was found to be negatively correlated to circulating platelet counts, and positively correlated with Interleukin (IL)-1β and IL-18. Notably, patients who exhibited poor response to corticosteroid treatment displayed elevated levels of TMAO and basic fibroblast growth factor (bFGF) in comparison to responders. Additionally, we found that the amalgamation of TMAO, bFGF and interleukin (IL)-13 could serve as a valuable prognostic tool for predicting CS responsiveness. Patients with ITP were characterized overall by an imbalanced secretion of cyto(cheo)kins/growth factors and inadequate levels of TMAO. The varying degrees of responsiveness to corticosteroid treatment can be attributed to different profiles of basic FGF and TMAO that might be related to overburdened oxidative stress and inflammasome overactivation, and ultimately mediate corticosteroid resistance. • Concentrations of TMAO were significantly suppressed in ITP patients. • CS non-responders showed elevated TMAO levels and decreased bFGF levels. • TMAO is related to oxidative stress and inflammasome signaling in CS non-responders. • Basic FGF might contribute to CS resistance by modulating SIRT1 regulated autophagy. • Combination of TMAO, bFGF, and IL-13 might be predictive for CS responsiveness. [ABSTRACT FROM AUTHOR]

With new advances in next generation sequencing (NGS) technology at reduced costs, research on bacterial genomes in the environment has become affordable. Compared to traditional methods, NGS provides high-throughput sequencing reads and the ability to identify many species in the microbiome that were previously unknown. Numerous bioinformatics tools and algorithms have been developed to conduct such analyses. However, in order to obtain biologically meaningful results, the researcher must select the proper tools and combine them to construct an efficient pipeline. This complex procedure may include tens of tools, each of which require correct parameter settings. Furthermore, an NGS data analysis involves multiple series of command-line tools and requires extensive computational resources, which imposes a high barrier for biologists and clinicians to conduct NGS analysis and even interpret their own data. Therefore, we established a public gut microbiome database, which we call Twnbiome, created using healthy subjects from Taiwan, with the goal of enabling microbiota research for the Taiwanese population. Twnbiome provides users with a baseline gut microbiome panel from a healthy Taiwanese cohort, which can be utilized as a reference for conducting case-control studies for a variety of diseases. It is an interactive, informative, and user-friendly database. Twnbiome additionally offers an analysis pipeline, where users can upload their data and download analyzed results. Twnbiome offers an online database which non-bioinformatics users such as clinicians and doctors can not only utilize to access a control set of data, but also analyze raw data with a few easy clicks. All results are customizable with ready-made plots and easily downloadable tables. Database URL: http://twnbiome.cgm.ntu.edu.tw/. [ABSTRACT FROM AUTHOR]

This study aimed to isolate and characterize probiotic Lactobacilli from human faecal samples of Jammu region of India and evaluation of their antioxidative properties. A total of 29 Lactobacillus strains were isolated and tested for their ability to withstand different pH levels, high concentrations of bile salt and lysozyme along with their adhesion ability to different hydrocarbons and auto-aggregation. Selected probiotic Lactobacillus isolates were further examined for their antioxidant potential using ABTS, DPPH methods, and the ability to scavenge superoxide and hydroxyl radicals. The results showed that Lactobacillus LpJ1 (7.93 ± 0.23) and LpJ5 (7.93 ± 0.59) had the highest cell viability at a pH of 2.5, while Lactobacillus LpJ16 (7.91 ± 0.48) had the highest resistance to bile salts. Many of the isolates also demonstrated good tolerance to lysozyme. The adhesion abilities of these isolates were characterized by cell surface hydrophobicity and auto aggregation which ranged between 50.32% to 77.8% and 51.02% to 78.95% respectively. In addition, Lactobacillus LpJ5 and LpJ8 showed excellent antioxidant activity. Based on these findings, the selected probiotic strains could be potential candidates for use in functional food to reduce oxidative stress. [ABSTRACT FROM AUTHOR]

Colon cancer remains one of the leading causes of morbidity and mortality worldwide. Given its widespread prevalence, the identification of new anticancer drugs is crucial. Medicinal plants have provided many natural products that have proven to be successful anticancer drugs in clinical use and have shown significant efficacy. Over the last decade, researchers have gathered significant information regarding the contribution of gut microbiota to the development and progression of colon cancer. Manipulating the gut microbiota to reverse microbial dysbiosis is an innovative strategy for addressing human diseases and intestinal disorders. Recent scientific findings have shown that this approach has a significant positive impact on the prevention and treatment of colon cancer. This review aims to provide a comprehensive understanding of the fundamental concepts related to intestinal microbiota and dysbiosis, as well as the interactions between microbiota and phytochemicals that can affect the bioavailability and bioactivity of these compounds. The primary components of the gut, including carbohydrates, enzymes, lipids, vitamins, and secondary metabolites such as alkaloids, flavonoids, polyphenols, and terpenoids, can activate gut dysbiosis. While these strategies show promising outcomes by rectifying microbiota proportion, modifying innate immune systems, emphasizing gut barrier operation, inhibiting pathogen colonization, and exhibiting selective cytotoxicity against colon cancer cells, further research is necessary to fully understand their mechanisms of action. This review also highlights the relationship between medicinal plants, gut microbiota, and colon cancer, which may lead to the development and clinical translation of potential microbiota-based strategies for cancer prevention.

Non-communicable diseases (NCDs) are significant threats faced by the global population. The root cause of NCDs is related to food consumption and diet pattern. Fermented foods are ingrained as part of traditions in many countries and serve as a carrier for probiotics. Recent research has correlated the quality of gut microbiota and the functioning and overall well-being of the body. Thus, the addition of fermented foods as a significant part of the diet can manage and prevent the development of many NCDs. This review aims to cumulate the current research and development carried out on fermented foods, probiotic potential, and their mechanism in managing selected NCDs.

Chronic inflammatory pain (CIP) is a common public medical problem, often accompanied by memory impairment. However, the mechanisms underlying CIP and comorbid memory impairment remain elusive. This study aimed to examine the role of the gut–microbiota–brain axis in CIP and comorbid memory impairment in mice treated with complete Freund's adjuvant (CFA). 16S rRNA analysis showed the altered diversity of gut microbiota from day 1 to day 14 after CFA injection. Interestingly, fecal microbiota transplantation (FMT) from healthy naive mice ameliorated comorbidities, such as mechanical allodynia, thermal hyperalgesia, spatial working memory impairment, neuroinflammation, and abnormal composition of gut microbiota in the CFA mice. Additionally, subdiaphragmatic vagotomy (SDV) blocked the onset of these comorbidities. Interestingly, the relative abundance of the bacterial genus or species was also correlated with these comorbidities after FMT or SDV. Therefore, our results suggest that the gut–microbiota–brain axis via the subdiaphragmatic vagus nerve is crucial for the development of CIP and comorbid spatial working memory impairment in CFA mice. [ABSTRACT FROM AUTHOR]

Obesity is a complex health condition that increases the susceptibility to developing cardiovascular diseases, diabetes, and numerous other metabolic health issues. The effect of obesity is not just limited to the conditions mentioned above; it is also seen to have a profound impact on the patient's mental state, leading to the onset of various mental disorders, particularly mood disorders. Therefore, it is necessary to understand the mechanism underlying the crosstalk between obesity and mental disorders. The gut microbiota is vital in regulating and maintaining host physiology, including metabolism and neuronal circuits. Because of this newly developed understanding of gut microbiota role, here we evaluated the published diverse information to summarize the achievement in the field. In this review, we gave an overview of the association between obesity, mental disorders, and the role of gut microbiota there. Further new guidelines and experimental tools are necessary to understand the microbial contribution to regulate a balanced healthy life. [ABSTRACT FROM AUTHOR]

Metabolic-dysfunction-associated fatty-liver disease (MAFLD) is the principal worldwide cause of liver disease. Individuals with nonalcoholic steatohepatitis (NASH) have a higher prevalence of small-intestinal bacterial overgrowth (SIBO). We examined gut-microbiota isolated from 12-week-old stroke-prone spontaneously hypertensive-5 rats (SHRSP5) fed on a normal diet (ND) or a high-fat- and high-cholesterol-containing diet (HFCD) and clarified the differences between their gut-microbiota. We observed that the Firmicute/Bacteroidetes (F/B) ratio in both the small intestines and the feces of the SHRSP5 rats fed HFCD increased compared to that of the SHRSP5 rats fed ND. Notably, the quantities of the 16S rRNA genes in small intestines of the SHRSP5 rats fed HFCD were significantly lower than those of the SHRSP5 rats fed ND. As in SIBO syndrome, the SHRSP5 rats fed HFCD presented with diarrhea and body-weight loss with abnormal types of bacteria in the small intestine, although the number of bacteria in the small intestine did not increase. The microbiota of the feces in the SHRSP5 rats fed HFCD was different from those in the SHRP5 rats fed ND. In conclusion, there is an association between MAFLD and gut-microbiota alteration. Gut-microbiota alteration may be a therapeutic target for MAFLD. [ABSTRACT FROM AUTHOR]

Background: Recent research on the implications of gut microbiota on brain functions has helped to gather important information on the relationship between them. Pathogenesis of neurological disorders is found to be associated with dysregulation of gut-brain axis. Some gut bacteria metabolites are found to be directly associated with the increase in reactive oxygen species levels, one of the most important risk factors of neurodegeneration. Besides their morbid association, gut bacteria metabolites are also found to play a significant role in reducing the onset of these life-threatening brain disorders. Aim of Review: Studies done in the recent past raises two most important link between gut microbiota and the brain: “gut microbiota-oxidative stress-neurodegeneration” and gut microbiota-antioxidant-neuroprotection. This review aims to gives a deep insight to our readers, of the collective studies done, focusing on the gut microbiota mediated oxidative stress involved in neurodegeneration along with a focus on those studies showing the involvement of gut microbiota and their metabolites in neuroprotection. Key Scientific Concepts of Review: This review is focused on three main key concepts. Firstly, the mounting evidences from clinical and preclinical arenas shows the influence of gut microbiota mediated oxidative stress resulting in dysfunctional neurological processes. Therefore, we describe the potential role of gut microbiota influencing the vulnerability of brain to oxidative stress, and a budding causative in Alzheimer's and Parkinson’s disease. Secondly, contributing roles of gut microbiota has been observed in attenuating oxidative stress and inflammation via its own metabolites or by producing secondary metabolites and, also modulation in gut microbiota population with antioxidative and anti-inflammatory probiotics have shown promising neuro resilience. Thirdly, high throughput in silico tools and databases also gives a correlation of gut microbiome, their metabolites and brain health, thus providing fascinating perspective and promising new avenues for therapeutic options.

Gut microbiota regulates essential processes of host metabolism and physiology: synthesis of vitamins, digestion of foods non-digestible by the host (such as fibers), and—most important—protects the digestive tract from pathogens. In this study, we focus on the CRISPR/Cas9 technology, which is extensively used to correct multiple diseases, including liver diseases. Then, we discuss the non-alcoholic fatty liver disease (NAFLD), affecting more than 25% of the global population; colorectal cancer (CRC) is second in mortality. We give space to rarely discussed topics, such as pathobionts and multiple mutations. Pathobionts help to understand the origin and complexity of the microbiota. Since several types of cancers have as target the gut, it is vital extending the research of multiple mutations to the type of cancers affecting the gut–liver axis. [ABSTRACT FROM AUTHOR]

Recent emerging research on intestinal microbiota and its contribution to the central nervous system during health and disease has attracted significant attention. Age-related intestinal microbiota changes initiate brain aging and age-related neurodegenerative disorders. Aging is one of the critical predisposing risk factors for the development of neurodegenerative diseases. Maintaining a healthy gut microbiota is essential for a healthy body and aging, but dysbiosis could initiate many chronic diseases. Understanding the underlying mechanisms of gut microbiota alterations/dysbiosis will help identify biomarkers for aging-related chronic conditions. This review summarizes recent advances in microbiota-neurodegenerative disease research and will enhance our understanding of gut microbiota dysbiosis and its effects on brain aging.

Multiple sclerosis (MS) is the most common demyelinating disease that attacks the central nervous system. Dietary intake of cuprizone (CPZ) produces demyelination resembling that of patients with MS. Given the role of the vagus nerve in gut–microbiota–brain axis in development of MS, we performed this study to investigate whether subdiaphragmatic vagotomy (SDV) affects demyelination in CPZ-treated mice. SDV significantly ameliorated demyelination and microglial activation in the brain compared with sham-operated CPZ-treated mice. Furthermore, 16S ribosomal RNA analysis revealed that SDV significantly improved the abnormal gut microbiota composition of CPZ-treated mice. An untargeted metabolomic analysis demonstrated that SDV significantly improved abnormal blood levels of metabolites in CPZ-treated mice compared with sham-operated CPZ-treated mice. Notably, there were correlations between demyelination or microglial activation in the brain and the relative abundance of several microbiome populations, suggesting a link between gut microbiota and the brain. There were also correlations between demyelination or microglial activation in the brain and blood levels of metabolites. Together, these data suggest that CPZ produces demyelination in the brain through the gut–microbiota–brain axis via the subdiaphragmatic vagus nerve.

Inflammatory bowel disease (IBD) is the most common form of intestinal inflammation associated with a dysregulated immune system response to the commensal microbiota in a genetically susceptible host. IBD includes ulcerative colitis (UC) and Crohn's disease (CD), both of which are remarkably heterogeneous in their clinical presentation and response to treatment. This translates into a notable diagnostic challenge, especially in underdeveloped countries where IBD is on the rise and access to diagnosis or treatment is not always accessible for chronic diseases. The present work characterized, for the first time in our region, epigenetic biomarkers and gut microbial profiles associated with UC and CD patients in the Buenos Aires Metropolitan area and revealed differences between non-IBD controls and IBD patients. General metabolic functions associated with the gut microbiota, as well as core microorganisms within groups, were also analyzed. Additionally, the gut microbiota analysis was integrated with relevant clinical, biochemical and epigenetic markers considered in the follow-up of patients with IBD, with the aim of generating more powerful diagnostic tools to discriminate phenotypes. Overall, our study provides new insights into data analysis algorithms to promote comprehensive phenotyping tools using quantitative and qualitative analysis in a transkingdom interactions network context. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease is neurodegenerative dementia which has significant health complications in the old age group. An imbalance in gut microbiota can influence to cause several diseases like chronic disorders, depression, type II diabetics, and neurological disorders like AD. Aging is one of the major causes of the development of neurodegenerative disease due to the decreasing levels of neurotransmitters, oxidative stress, chronic inflammation, and apoptosis. These harmful effects of aging can be prevented by probiotics usage. The gut-microbiota is capable to control the brain function through the gut-brain axis. Lactobacillus strains are considered as beneficial microorganism because of its importance of the maintenance in healthy intestinal microflora, immunomodulation, and intestinal pathogenic intervention. They have diverse applications in the medical field with properties like antioxidant, anticancer, anti-inflammatory, anti-proliferative, anti-obesity, and anti-diabetic activities. Probiotic supplementation with Lactobacillus strains shows an optimistic trend to use it as a significant therapy for cognitive symptoms. This review article put forwards the significance of the gut-brain axis and the contribution of Lactobacillus strains as a probiotic supplement and its therapeutic innovations for future aspects and the limitation to treat AD-related pathogenesis are briefly elucidated.

The strong association between gut microbiota (GM) and brain functions such as mood, behaviour, and cognition has been well documented. Gut-brain axis is a unique bidirectional communication system between the gut and brain, in which gut microbes play essential role in maintaining various molecular and cellular processes. GM interacts with the brain through various pathways and processes including, metabolites, vagus nerve, HPA axis, endocrine system, and immune system to maintain brain homeostasis. GM dysbiosis, or an imbalance in GM, is associated with several neurological disorders, including anxiety, depression, and Alzheimer's disease (AD). Conversely, AD is sustained by microglia-mediated neuroinflammation and neurodegeneration. Further, GM and their products also affect microglia-mediated neuroinflammation and neurodegeneration. Despite the evidence connecting GM dysbiosis and AD progression, the involvement of GM in modulating microglia-mediated neuroinflammation in AD remains elusive. Importantly, deciphering the mechanism/s by which GM regulates microglia-dependent neuroinflammation may be helpful in devising potential therapeutic strategies to mitigate AD. Herein, we review the current evidence regarding the involvement of GM dysbiosis in microglia activation and neuroinflammation in AD. We also discuss the possible mechanisms through which GM influences the functioning of microglia and its implications for therapeutic intervention. Further, we explore the potential of microbiota-targeted interventions, such as prebiotics, probiotics, faecal microbiota transplantation, etc., as a novel therapeutic strategy to mitigate neuroinflammation and AD progression. By understanding and exploring the gut-brain axis, we aspire to revolutionize the treatment of neurodegenerative disorders, many of which share a common theme of microglia-mediated neuroinflammation and neurodegeneration. • GM dysbiosis, or an imbalance in GM, is associated with neurological diseases, including Alzheimer's disease (AD). • GM maintains brain homeostasis through interactions with the vagus nerve, HPA axis, endocrine system, and immune system. • GM and their products influence the microglia-mediated neuroinflammation and neurodegeneration. • Understanding the impact of GM on microglia-mediated neuroinflammation could help develop disease-modifying treatment for AD. • Probiotics, FMT etc. offer innovative therapeutic options to reduce microglia-mediated neuroinflammation and AD pathogenesis. [ABSTRACT FROM AUTHOR]

Human body is colonized by a complex ecosystem of microbes that play a significant role in determining the fitness of the host. The epigenetic signatures of probiotic microorganisms also define the functional role of microbiota in the intestine and further facilitate exploring their beneficial properties. Development in the areas of molecular biology and genomics has paved way for engineering of microorganisms. The advent of genome editing tools such as CRISPR-Cas, has revolutionized new possibilities for genetic engineering in probiotics for enhanced immune response, antimicrobial properties and applications in biotherapeutics. Here, we discuss the present status of genome editing used in epigenome engineering of the gut microbiota and role of different types of CRISPR-Cas systems. Applications of CRISPR-Cas system can be harnessed to modify probiotic microbes in order to regulate gene expressions and produce desired metabolite. These techniques illuminate novel approaches to metabolic engineering and draw attention towards poorly characterized biosynthetic pathways. In addition, future prospects of these tools can be applied to investigate the interactions between gut microbiome and the host, hence, contributing to the development of novel therapeutics. [ABSTRACT FROM AUTHOR]

Respiratory diseases are responsible for a greater mortality rate around the world. Viral or bacterial infections in the respiratory tract have been identified as major causative agents for death and disability among the population. Respiratory tract infections (RTIs) cause severe respiratory ailments starting from coldlike symptoms, eventually affecting the lungs and other viscera, and are mainly categorized into two types depending on the affected area: upper RTIs and lower RTIs. Respiratory viruses belong to several viral families such as influenza virus, enterovirus, adenovirus, respiratory syncytial virus, and recently severe acute respiratory syndrome coronavirus 2. Studies have indicated that people with good immune functions are less prone to respiratory infections and also their recovery rate is quicker. Innate and acquired immune systems actively participate in the recognition and elimination of the pathogenic agents. In the present context, the potential of probiotics is recognized as viable microorganisms that support the balance of the beneficial microbial population in the gastrointestinal tract and promote host immunity. The probiotics have long been known to regulate bodily immune functions and have been used against general RTIs such as cough, pharyngitis, laryngitis, pneumonia, and asthma. In addition, intervention with probiotics could directly affect the composition of the gut microbiota that have been shown to palliate respiratory diseases by modulating pulmonary immune activities through the gut–lung axis, and therefore, probiotics could become an alternative therapeutic approach for RTIs. [ABSTRACT FROM AUTHOR]

It is well appreciated that there is a female preponderance in the development of most autoimmune diseases. Thought to be due to a complex interplay between sex chromosome complement and sex-hormones, however, the exact mechanisms underlying this sex-bias remain unknown. In recent years, there has been a focus on understanding the central pathogenic role of the bacteria that live in the gut, or the gut-microbiota, in the development of autoimmunity. In this review, we discuss evidence from animal models demonstrating that the gut-microbiota is sexually dimorphic, that there is a bidirectional relationship between the production of sex-hormones and the gut-microbiota, and that this sexual dimorphism within the gut-microbiota may influence the sex-bias observed in autoimmune disease development. Collectively, these data underline the importance of considering sex as a variable when investigating biological pathways that contribute to autoimmune disease risk.

[Display omitted] • Owing to high O 2 consumption, brain is highly vulnerable to oxidative stress. • Gut-brain axis act as a vital pathway of communication and physiological regulation. • Altered gut microbiota-mediated oxidative stress is associated with neurodegeneration. • Healthy gut microbiota has an immense antioxidative and anti-inflammatory role. • Antioxidative prebiotics and probiotics attenuates neurodegenerative symptoms. • Current databases and in silico tools will help to develop new therapeutic regimens. Recent research on the implications of gut microbiota on brain functions has helped to gather important information on the relationship between them. Pathogenesis of neurological disorders is found to be associated with dysregulation of gut-brain axis. Some gut bacteria metabolites are found to be directly associated with the increase in reactive oxygen species levels, one of the most important risk factors of neurodegeneration. Besides their morbid association, gut bacteria metabolites are also found to play a significant role in reducing the onset of these life-threatening brain disorders. Studies done in the recent past raises two most important link between gut microbiota and the brain: "gut microbiota-oxidative stress-neurodegeneration" and gut microbiota-antioxidant-neuroprotection. This review aims to gives a deep insight to our readers, of the collective studies done, focusing on the gut microbiota mediated oxidative stress involved in neurodegeneration along with a focus on those studies showing the involvement of gut microbiota and their metabolites in neuroprotection. This review is focused on three main key concepts. Firstly, the mounting evidences from clinical and preclinical arenas shows the influence of gut microbiota mediated oxidative stress resulting in dysfunctional neurological processes. Therefore, we describe the potential role of gut microbiota influencing the vulnerability of brain to oxidative stress, and a budding causative in Alzheimer's and Parkinson's disease. Secondly, contributing roles of gut microbiota has been observed in attenuating oxidative stress and inflammation via its own metabolites or by producing secondary metabolites and, also modulation in gut microbiota population with antioxidative and anti-inflammatory probiotics have shown promising neuro resilience. Thirdly, high throughput in silico tools and databases also gives a correlation of gut microbiome, their metabolites and brain health, thus providing fascinating perspective and promising new avenues for therapeutic options. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is the most common demyelinating disease that attacks the central nervous system. We recently reported that the new antidepressant (R)-ketamine could ameliorate the disease progression in experimental autoimmune encephalomyelitis model of MS. Cuprizone (CPZ) has been used to produce demyelination which resembles demyelination in MS patients. This study was undertaken to investigate whether (R)-ketamine could affect demyelination in CPZ-treated mice and remyelination after CPZ withdrawal. Repeated treatment with (R)-ketamine (10 mg/kg/day, twice weekly, for 6 weeks) significantly ameliorated demyelination and activated microglia in the brain compared with saline-treated mice. Furthermore, pretreatment with ANA-12 (TrkB antagonist) significantly blocked the beneficial effects of (R)-ketamine on the demyelination and activated microglia in the brain of CPZ-treated mice. The 16S rRNA analysis showed that (R)-ketamine significantly improved abnormal composition of gut–microbiota and decreased levels of lactic acid of CPZ-treated mice. In addition, there were significant correlations between demyelination (or microglial activation) in the brain and the relative abundance of several microbiome, suggesting a link between gut microbiota and brain. Interestingly, (R)-ketamine could facilitate remyelination in the brain after CPZ withdrawal. In conclusion, the study suggests that (R)-ketamine could ameliorate demyelination in the brain of CPZ-treated mice through TrkB activation, and that gut–microbiota–microglia crosstalk may play a role in the demyelination of CPZ-treated mice. Therefore, it is likely that (R)-ketamine could be a new therapeutic drug for MS.

Obesity is a complex health condition that increases the susceptibility to developing cardiovascular diseases, diabetes, and numerous other metabolic health issues. The effect of obesity is not just limited to the conditions mentioned above; it is also seen to have a profound impact on the patient’s mental state, leading to the onset of various mental disorders, particularly mood disorders. Therefore, it is necessary to understand the mechanism underlying the crosstalk between obesity and mental disorders. The gut microbiota is vital in regulating and maintaining host physiology, including metabolism and neuronal circuits. Because of this newly developed understanding of gut microbiota role, here we evaluated the published diverse information to summarize the achievement in the field. In this review, we gave an overview of the association between obesity, mental disorders, and the role of gut microbiota there. Further new guidelines and experimental tools are necessary to understand the microbial contribution to regulate a balanced healthy life.

Probiotics are living organisms that offer the host health advantages when taken in sufficient amounts. The aim of the study was to evaluate pediatricians' probiotic knowledge and practice patterns across different geographical areas. The purpose of this study is to examine 350 students from the Department of Genetic Engineering and Biotechnology at the University of Rajshahi in Bangladesh to see what information, attitudes, and perceptions they have regarding probiotics. 350 people gladly answered the questionnaire, even though it was distributed among 400 participants. The questionnaire that was self-administered was used to gather data. The data were computed using simple tools. 53.2% of the participants in this case were female. Even though all of the participants were from the biology department, 31.5% of them had never heard of probiotics. The majority of respondents (65%) identified yogurt as the most important source of probiotics. Only 30% of participants were aware that gut microbiota and diabetes are related, despite 46.8% of participants having a family history of the disease. A major worldwide concern is emerging from antibiotic resistance. Approximately 75% of participants used antibiotics without a doctor's prescription, and 63.7% were unaware that medications may damage the gut microbiota. The most encouraging finding of the study was that 90.3% of participants would take probiotics as a medicine if their doctor suggested it. Many people still have disagreements concerning probiotics, and the subject is not well understood. The participants' knowledge of probiotics also varies greatly. To be able to reach the greatest number of people and encourage the development of a healthy generation, this gap needs to be addressed on various levels.

Aflatoxin B1 (AFB1) induced intestinal epithelial damage in rodent models, which indicates that long-term exposure to AFB1 may cause chronic gut disorders. In this study, we tested the hypothesis that AFB1-induced adverse effects on gut is mediated by gut-microbiota, which is partially reflected by the changes of fecal microbiome and metabolome. F344 rats were orally exposed to AFB1 of 0, 5, 25, and 75 µg kg−1 body weight for 4 weeks and fecal samples were collected. An ion-fragmentation-spectrum-based metabolomics approach was developed to investigate the fecal microbiota-associated metabolic changes in fecal samples. We found that AFB1 inhibited the hepatic and intestinal metabolism of bile constituents. As compared with the controls, bile acid synthesis-associated cholesterols in rats treated with 25 µg kg−1 (the middle-dose group) were significantly decreased in the fecal samples, for example, lathosterol (45% reduction), cholesterol ester (21% reduction), chenodeoxycholic acid (20% reduction), dihydroxycholesterol (55% reduction), hydroxycholesterol (20% reduction), and 5-cholestene (29% reduction). Although disease-associated lipids were not detectable in the feces of the control group, they were found in AFB1-treated groups, including diglyceride, monoacylglyceride, 19,20-dihydroxy-docosapentaenoic acid, and phosphatidylethanolamine. Metabolisms of carbohydrates and production of short-chain fatty acids were remarkedly decreased in all treated groups. Moreover, an inflammatory-bowel-disease (IBD)-associated taxonomic structure of fecal microbiota was observed as ∼25% Lachnospiraceae , ∼25% Ruminococcaceae , and <1% Lactobacillales , which was similar to the composition pattern found in IBD patients. These results suggest that AFB1-induced disruption on gut-microbiota, partially reflected by fecal microbiome and metabolome, may play important roles in the pathogenesis of chronic gut disorders. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease is neurodegenerative dementia which has significant health complications in the old age group. An imbalance in gut microbiota can influence to cause several diseases like chronic disorders, depression, type II diabetics, and neurological disorders like AD. Aging is one of the major causes of the development of neurodegenerative disease due to the decreasing levels of neurotransmitters, oxidative stress, chronic inflammation, and apoptosis. These harmful effects of aging can be prevented by probiotics usage. The gut-microbiota is capable to control the brain function through the gut-brain axis. Lactobacillus strains are considered as beneficial microorganism because of its importance of the maintenance in healthy intestinal microflora, immunomodulation, and intestinal pathogenic intervention. They have diverse applications in the medical field with properties like antioxidant, anticancer, anti-inflammatory, anti-proliferative, anti-obesity, and anti-diabetic activities. Probiotic supplementation with Lactobacillus strains shows an optimistic trend to use it as a significant therapy for cognitive symptoms. This review article put forwards the significance of the gut-brain axis and the contribution of Lactobacillus strains as a probiotic supplement and its therapeutic innovations for future aspects and the limitation to treat AD-related pathogenesis are briefly elucidated. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is the most common form of intestinal inflammation associated with a dysregulated immune system response to the commensal microbiota in a genetically susceptible host. IBD includes ulcerative colitis (UC) and Crohn’s disease (CD), both of which are remarkably heterogeneous in their clinical presentation and response to treatment. This translates into a notable diagnostic challenge, especially in underdeveloped countries where IBD is on the rise and access to diagnosis or treatment is not always accessible for chronic diseases. The present work characterized, for the first time in our region, epigenetic biomarkers and gut microbial profiles associated with UC and CD patients in the Buenos Aires Metropolitan area and revealed differences between non-IBD controls and IBD patients. General metabolic functions associated with the gut microbiota, as well as core microorganisms within groups, were also analyzed. Additionally, the gut microbiota analysis was integrated with relevant clinical, biochemical and epigenetic markers considered in the follow-up of patients with IBD, with the aim of generating more powerful diagnostic tools to discriminate phenotypes. Overall, our study provides new insights into data analysis algorithms to promote comprehensive phenotyping tools using quantitative and qualitative analysis in a transkingdom interactions network context.

Human milk is the gold standard for infant nutrition. Preterm infants whose mothers are unable to provide sufficient own mother's milk (OMM), receive pasteurized donor human milk (DHM). We studied metabolic signatures of OMM and DHM and their effect on the interplay of the developing microbiota and infant's metabolism. Metabolic fingerprinting of OMM and DHM as well as infant's urine was performed using liquid chromatography–mass spectrometry and the infant's stool microbiota was analyzed by 16S rRNA sequencing. Significant differences in the galactose and starch and sucrose metabolism pathways when comparing OMM and DHM, and alterations of the steroid hormone synthesis and pyrimidine metabolism pathways in urine were observed depending on the type of feeding. Differences in the gut-microbiota composition were also identified. The composition of DHM differs from OMM and feeding of DHM has a significant impact on the metabolic phenotype and microbiota of preterm infants. Our data help to understand the origin of the observed changes generating new hypothesis: i) steroid hormones present in HM have a significant influence in the activity of the steroid hormone biosynthesis pathway in preterm infants; ii) the pyrimidine metabolism is modulated in preterm infants by the activity of gut-microbiota. Short- and long-term implications of the observed changes for preterm infants need to be assessed in further studies. [ABSTRACT FROM AUTHOR]

Acute aortic dissection (AAD) is the most severe traumatic disease affecting the aorta. Pyroptosis-mediated vascular wall inflammation is a crucial trigger for AAD, and the exact mechanism requires further investigation. In this study, our proteomic analysis showed that Lipopolysaccharide (LPS)-binding protein (LBP) was significantly upregulated in the plasma and aortic tissue of patients with AAD. Further, 16S rRNA sequencing of stool samples suggested that patients with AAD exhibit gut dysbiosis, which may lead to an impaired intestinal barrier and LPS leakage. By comparing with control mice, we found that LBP, including Pyrin Domain Containing Protein3 (NLRP3), the CARD-containing adapter apoptosis-associated speck-like protein (ASC), and Cleaved caspase-1, were upregulated in the AAD aorta, whereas gut intestinal barrier-related proteins were downregulated. Moreover, treated with LBPK95A (an LBP inhibitor) attenuated the incidence of AAD, the expression levels of pyroptosis-related factors, and the extent of vascular pathological changes compared to those in AAD mice. In addition, LPS and LBP treatment of human umbilical vein endothelial cells (HUVECs) activated TLR4 signaling and intracellular reactive oxygen species (ROS) production, which stimulated NLRP3 inflammasome formation and mediated pyroptosis in endothelial cells. Our findings showed that gut dysbiosis mediates pyroptosis by the LPS-LBP complex, thus providing new insights into developing AAD., Competing Interests: Declaration of competing interest All the authors declare that they have no competing interests., (Copyright © 2024 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

An association between gut–microbiota and several neuropsychiatric conditions including autism, depression, anxiety, schizophrenia, and attention-deficit/hyperactivity disorder (ADHD) has been observed. Despite being the most prevalent neurodevelopmental disorders in children and adolescents worldwide, the etiology and curative approaches to treatment of ADHD remain unclear. There is a probability that gut–microbiota may contribute to ADHD via bidirectional communication between the gut and brain, a system known as the "gut–brain axis". Although a mechanistic link in the gut–brain axis in ADHD has been proposed, there is still a lack of information about the correlation of the microbiome profile with the mechanisms involved. The objective of this review was to summarize the diversity of the gut–microbiota and taxonomic profiles in children and adolescents with ADHD. In this review, we have provided an overview of the association between ADHD and gut–microbiota. The evidence pertinent to potentially distinctive gut–microbiota in children and adolescents with ADHD is also discussed and compared to that of their non-ADHD peers. Finally, the implications and future directions for investigation into the gut microbiome in ADHD patients are proposed. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that food ingested polyphenols can have beneficial effects in neuronal protection acting against oxidative stress and inflammatory injury. Moreover, polyphenols have been reported to promote cognitive functions. Biotransformation of polyphenols is needed to obtain metabolites active in brain and it occurs through their processing by gut microbiota. Polyphenols metabolites could directly act as neurotransmitters crossing the blood-brain barrier or indirectly by modulating the cerebrovascular system. The microbiota-gut-brain axis is considered a neuroendocrine system that acts bidirectionally and plays an important role in stress responses. The metabolites produced by microbiota metabolism can modulate gut bacterial composition and brain biochemistry acting as neurotransmitters in the central nervous system. Gut microbiota composition can be influenced by dietary ingestion of natural bioactive molecules such as probiotics, prebiotics and polyphenol. Microbiota composition can be altered by dietary changes and gastrointestinal dysfunctions are observed in neurodegenerative diseases. In addition, several pieces of evidence support the idea that alterations in gut microbiota and enteric neuroimmune system could contribute to onset and progression of these age-related disorders. The impact of polyphenols on microbiota composition strengthens the idea that maintaining a healthy microbiome by modulating diet is essential for having a healthy brain across the lifespan. Moreover, it is emerging that they could be used as novel therapeutics to prevent brain from neurodegeneration.

The endocannabinoid system (ECS) has emerged in recent years as a potential treatment target for alcohol use disorders (AUD). In particular, the nonpsychoactive cannabinoid cannabidiol (CBD) has shown preclinical promise in ameliorating numerous clinical symptoms of AUD. There are several proposed mechanism(s) through which cannabinoids (and CBD in particular) may confer beneficial effects in the context of AUD. First, CBD may directly impact specific brain mechanisms underlying AUD to influence alcohol consumption and the clinical features of AUD. Second, CBD may influence AUD symptoms through its actions across the digestive, immune, and central nervous systems, collectively known as the microbiota–gut–brain axis (MGBA). Notably, emerging work suggests that alcohol and cannabinoids exert opposing effects on the MGBA. Alcohol is linked to immune dysfunction (e.g., chronic systemic inflammation in the brain and periphery) as well as disturbances in gut microbial species (microbiota) and increased intestinal permeability. These MGBA disruptions have been associated with AUD symptoms such as craving and impaired cognitive control. Conversely, existing preclinical data suggest that cannabinoids may confer beneficial effects on the gastrointestinal and immune system, such as reducing intestinal permeability, regulating gut bacteria, and reducing inflammation. Thus, cannabinoids may exert AUD harm‐reduction effects, at least in part, through their beneficial actions across the MGBA. This review will provide a brief introduction to the ECS and the MGBA, discuss the effects of cannabinoids (particularly CBD) and alcohol in the brain, gut, and immune system (i.e., across the MGBA), and put forth a theoretical framework to inform future research questions. [ABSTRACT FROM AUTHOR]

This study underpins the therapeutic potential of SEL001, a bioactive product isolated from Lactobacillus sakei probio65, in terms of its anti-inflammatory properties and its effect on gut-microbiota in a TNBS-induced ulcerative colitis mouse model. Ulcerative colitis was developed in mice by intra rectal administration of trinitrobenzene sulfonic acid. Bioactive product SEL001 (50 mg/kg b.w.) was administered orally. Myeloperoxidase activity was measured using 3,3′, 5,5′-tetramethylbenzidine. The entire colon was sampled for post-mortem clinical assessment. Colonic injury was assessed through histological and histomorphometric examinations. The 454 pyrosequencing and QIIME pipeline were used for gut microbiota analysis and statistical analysis were conducted using R. mRNA extraction from colon tissue and RT-PCR approaches were employed to determine the changes in the level of specific biomarker genes associated with UC. The results depict that SEL001 significantly lowered pro-inflammatory cytokines, including CD4, TNF-α, and interleukin-6. Examination of clinical and histopathological traits revealed that SEL001 was effective and potent in reducing the inflammatory signatures of UC to a similar extent as did by the standard drug mesalamine (5-ASA). Pyro-sequencing 16S data revealed that the reduction in the major member of phylum Firmicutes, which has been previously associated with a higher risk of UC. The SEL001, an anti-inflammatory bioactive product originated from a probiotic strain L. sakei probio65 could be an alternative therapeutic agent for treatment of UC. [ABSTRACT FROM AUTHOR]

Introduction: Worldwide, obesity poses a serious threat to public health and leads to higher costs and diseases. New research has shown that gut microbiota have a significant impact on how obesity and other metabolic problems are treated. Ginger is used as a spice and dietary supplement. It reduces inflammation and oxidative stress in the body and may have potential for treating obesity. The aim of the study was to investigate the beneficial effects of ginger in preventing obesity through the regulation of gut microbiota. Method: This review was conducted by searching databases including PubMed, Web of Science, Scopus, and Google Scholar. The keywords "obesity," "Gut-microbiota," and "Ginger" were examined without time limitation. English-language studies that investigated the Beneficial effects of ginger on prevention of obesity through modulation of gut microbiota met the study inclusion criteria. Findings: A total of 753 articles were obtained, out of which 14 related articles were entered for review. In 9 studies (64%), the beneficial role of ginger in preventing obesity through regulating gut microbes was mentioned. In 5 articles (35%), the direct effect of ginger in weight reduction and improvement of obesity-related diseases was also highlighted, and it was concluded the use of ginger supplement has a therapeutic effect. Conclusion: Although the impact of ginger on gut microbiota for preventing obesity still requires further investigation, the positive effects in the studied articles show incorporating ginger into weight loss and obesity treatment regimens can be beneficial. [ABSTRACT FROM AUTHOR]

Mucosal-associated invariant T (MAIT) cells are a subset of T lymphocytes expressing a semi-invariant T-cell receptor (TCR) present as TCR Vα7.2-Jα33 in humans and TCR Vα19-Jα33 in mice. They are activated by ligands produced during microbial biosynthesis of riboflavin that is presented by major histocompatibility complex class I-related (MR1) molecules on antigen-presenting cells. MAIT cells also possess interleukin (IL)-12 and IL-18 receptors and can be activated by the respective cytokines released from microbially stimulated antigen-presenting cells. Therefore, MAIT cells can be involved in bacterial and viral defenses and are a significant part of the human immune system. They are particularly abundant in the liver, an organ serving as the second firewall of gut microbes next to the intestinal barrier. Therefore, the immune functions of MAIT cells are greatly impacted by changes in the gut-microbiota and play important roles in the gut-liver pathogenesis axis. In this review, we discuss the nature and mechanisms of MAIT cell activation and their dynamics during different types of liver pathogenesis conditions. We also share our perspectives on important aspects that should be explored further to reveal the exact roles that MAIT cells play in liver pathogenesis in the context of the gut microbiota.

The gut–liver axis plays important roles in both the maintenance of a healthy liver and the pathogenesis of liver diseases, where the gut microbiota acts as a major determinant of this relationship. Gut bacteria-derived metabolites and cellular components are key molecules that affect the function of the liver and modulate the pathology of liver diseases. Accumulating evidence showed that gut microbiota produces a myriad of molecules, including lipopolysaccharide, lipoteichoic acid, peptidoglycan, and DNA, as well as short-chain fatty acids, bile acids, trimethylamine, and indole derivatives. The translocation of these components to the liver exerts beneficial or pathogenic effects by interacting with liver immune cells. This is a bidirectional relationship. Therefore, the existence of crosstalk between the gut and liver and its implications on host health and diseases are essential for the etiology and treatment of diseases. Several mechanisms have been proposed for the pathogenesis of liver diseases, but still, the mechanisms behind the pathogenic role of gut-derived components on liver pathogenesis remain elusive and not understandable. This review discusses the current progress on the gut microbiota and its components in terms of the progression of liver diseases, and in turn, how liver diseases indirectly affect the intestinal function and induce intestinal inflammation. Moreover, this paper highlights the current therapeutic and preventive strategies used to restore the gut microbiota composition and improve host health.

The human body is a complex ecosystem that thrives on symbiosis. It is estimated that around 10^14 commensal microorganisms inhabit the human body, with the gut microbiota being one of the most diverse and complex populations of bacteria. This community is thought to comprise over a thousand different species that play a crucial role in the development of critical human diseases such as cancer, obesity, diabetes, mental depression, hypertension, and others. The gut microbiota has been identified as one of the most recent contributors to these metabolic disorders. With the emergence of inexpensive and high-performance sequence technology, our understanding of the function of the intestinal microbiome in host metabolism regulation and the development of (cardio) metabolic diseases has increased significantly. The symbiotic relationship between the gut microbiota and the host is essential for properly developing the human metabolic system. However, if this balance is disrupted by various factors such as infection, diet, exercise, sleep patterns, or exposure to antibiotics, it can lead to the development of various diseases in the body, including obesity and diabetes type 1 and 2. While many approaches and medications have been developed globally to treat these diseases, none have proven to be entirely effective, and many show side effects. Therefore, scientists believe that treating the gut microbiota using tried-and-true methods is the best option for combating obesity and diabetes. In this study, we aim to identify several feasible ways and prospects for gut microbiota therapy that can shape a new format for the treatment of obesity and diabetes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Backgrounds: Postbiotics produced by gut microbiota have exhibited diverse pharmacological activities. Valeric acid, a postbiotic material produced by gut microbiota and some plant species like valerian, has been explored to have diverse pharmacological activities., Methods: This narrative review aims to summarise the beneficial role of valeric acid for different health conditions along with its underlying mechanism. In order to get ample scientific evidence, various databases like Science Direct, PubMed, Scopus, Google Scholar and Google were exhaustively explored to collect relevant information. Collected data were arranged and analyzed to reach a meaningful conclusion regarding the bioactivity profiling of valeric acid, its mechanism, and future prospects., Results: Valeric acid belongs to short-chain fatty acids (SCFAs) compounds like acetate, propionate, butyrate, pentanoic (valeric) acid, and hexanoic (caproic) acid. Valeric acid has been identified as one of the potent histone deacetylase (HDAC) inhibitors. In different preclinical in -vitro and in-vivo studies, valeric acid has been found to have anti-cancer, anti-diabetic, antihypertensive, anti-inflammatory, and immunomodulatory activity and affects molecular pathways of different diseases like Alzheimer's, Parkinson's, and epilepsy., Conclusion: These findings highlight the role of valeric acid as a potential novel therapeutic agent for endocrine, metabolic and immunity-related health conditions, and it must be tested under clinical conditions to develop as a promising drug., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Abstract Atypical antipsychotics (AAPs) are the drug of choice in the management of mental illnesses by virtue of their advantage over typical antipsychotics i.e. least tendency of producing extrapyramidal motor symptoms (EPS) or pseudoparkinsonism. Despite the clinical efficacy, AAPs produces troublesome adverse effects, particularly hyperphagia, hyperglycemia, dyslipidemia weight gain, diabetes mellitus, insulin resistance and QT prolongation which further develops metabolic and cardiac complications with subsequent reduction in life expectancy, poor patient compliance, and sudden death. AAPs-induced weight gain and metabolic alterations are increasing at an alarming rate and became an utmost matter of concern for psychopharmacotherapy. Diverse underlying mechanisms have been explored such as the interaction of AAPs with neurotransmitter receptors, alteration in food reward anticipation behavior, altered expressions of hypothalamic orexigenic and anorexigenic neuropeptides, histamine H 1 receptor-mediated hypothalamic AMP-activated protein kinase (AMPK) activation, increased blood leptin, ghrelin, pro-inflammatory cytokines. Antipsychotics induced imbalance in energy homeostasis, reduction in energy expenditure which is linked to altered expression of uncoupling proteins (UCP-1) in brown adipose tissue and reduced hypothalamic orexin expressions are emerging insights. In addition, alteration in gut-microbiota and subsequent inflammation, dyslipidemia, obesity, and diabetes after AAPs treatment are also associated with weight gain and metabolic alterations. Oral hypoglycemics and lipid-lowering drugs are mainly prescribed in the clinical management of weight gain associated with AAPs while many other pharmacological and nonpharmacological interventions also have been explored in different clinical and preclinical studies. In this review, we critically discuss the current scenario, mechanistic insights, biomarkers, and therapeutic alternatives for metabolic alterations associated with antipsychotics. [ABSTRACT FROM AUTHOR]