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The intestinal lumen is a turbulent, semi-fluid landscape where microbial cells and nutrient-rich particles are distributed with high heterogeneity. Major questions regarding the basic physical structure of this dynamic microbial ecosystem remain unanswered. Most gut microbes are non-motile, and it is unclear how they achieve optimum localization relative to concentrated aggregations of dietary glycans that serve as their primary source of energy. In addition, a random spatial arrangement of cells in this environment is predicted to limit sustained interactions that drive co-evolution of microbial genomes. The ecological consequences of random versus organized microbial localization have the potential to control both the metabolic outputs of the microbiota and the propensity for enteric pathogens to participate in proximity-dependent microbial interactions. Here, we review evidence suggesting that several bacterial species adopt organized spatial arrangements in the gut via adhesion. We highlight examples where localization could contribute to antagonism or metabolic interdependency in nutrient degradation, and we discuss imaging- and sequencing-based technologies that have been used to assess the spatial positions of cells within complex microbial communities.

This article summarises the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organised by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: (1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g. genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomisation in humans; (2) the highly individualised nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; (3) because single time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and (4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.

INTRODUCTION: A large proportion of patients with inflammatory bowel disease (IBD) experience IBD-related inflammatory conditions outside of the gastrointestinal tract, termed extraintestinal manifestations (EIMs) which further decreases quality of life and, in extreme cases, can be life threatening. The pathogenesis of EIMs remains unknown, and although gut microbiota alterations are a well-known characteristic of patients with IBD, its relationship with EIMs remains sparsely investigated. This study aimed to compare the gut microbiota of patients with IBD with and without EIMs. METHODS: A total of 131 Danish patients with IBD were included in the study, of whom 86 had a history of EIMs (IBD-EIM) and 45 did not (IBD-C). Stool samples underwent 16S rRNA sequencing. Amplicon sequence variants (ASVs) were mapped to the Silva database. Diversity indices and distance matrices were compared between IBD-EIM and IBD-C. Differentially abundant ASVs were identified using a custom multiple model statistical analysis approach, and modules of co-associated bacteria were identified using sparse correlations for compositional data (SparCC) and related to patient EIM status. RESULTS: Patients with IBD and EIMs exhibited increased disease activity, body mass index, increased fecal calprotectin levels and circulating monocytes and neutrophils. Microbiologically, IBD-EIM exhibited lower fecal microbial diversity than IBD-C (Mann-Whitneys test, p = .01) and distinct fecal microbiota composition (permutational multivariate analysis of variance; weighted UniFrac, R2 = 0.018, p = .01). A total of 26 ASVs exhibited differential relative abundances between IBD-EIM and IBD-C, including decreased Agathobacter and Blautia and increased Eggerthella lenta in the IBD-EIM group. SparCC analysis identified 27 bacterial co-association modules, three of which were negatively related to EIM (logistic regression, p

Gut microbiota can influence host gene expression and physiology through metabolites. Besides, the presence or absence of gut microbiome can reprogram host transcriptome and epitranscriptome as represented by N6-methyladenosine (m6A), the most abundant mammalian mRNA modification. However, which and how gut microbiota-derived metabolites reprogram host transcriptome and m6A epitranscriptome remain poorly understood. Here, investigation is conducted into how gut microbiota-derived metabolites impact host transcriptome and m6A epitranscriptome using multiple mouse models and multi-omics approaches. Various antibiotics-induced dysbiotic mice are established, followed by fecal microbiota transplantation (FMT) into germ-free mice, and the results show that bile acid metabolism is significantly altered along with the abundance change in bile acid-producing microbiota. Unbalanced gut microbiota and bile acids drastically change the host transcriptome and the m6A epitranscriptome in multiple tissues. Mechanistically, the expression of m6A writer proteins is regulated in animals treated with antibiotics and in cultured cells treated with bile acids, indicating a direct link between bile acid metabolism and m6A biology. Collectively, these results demonstrate that antibiotic-induced gut dysbiosis regulates the landscape of host transcriptome and m6A epitranscriptome via bile acid metabolism pathway. This work provides novel insights into the interplay between microbial metabolites and host gene expression.

BackgroundLabor epidural analgesia (LEA) may influence gut microbiota. We explored the association between LEA and gut microbiota for both mothers and their newborns.MethodsIn this prospective cohort study, parturients aged 25-35 years with a gestational age of 37-42 weeks and planned vaginal delivery were recruited. Twenty-one parturients received LEA (the LEA group), and 24 did not (the control group). Maternal and neonatal fecal samples were collected, and the gut microbiota profiles were analyzed using the 16S rRNA gene sequencing. The impact of LEA on gut microbiota was assessed using the general liner models.ResultsWe showcased the gut microbiota profile from the phyla to species levels based on data on 45 mother-newborn dyads. The results of α- and β-diversity suggested significant changes in gut microbiota between the LEA and control groups. After adjusting for baseline confounders, the administration of LEA had positive correlations with R. ilealis (β = 91.87, adjusted P = 0.007) in mothers; LEA also had negative correlations with A. pittii (β = -449.36, adjusted P = 0.015), P. aeruginosa (β = -192.55, adjusted P = 0.008), or S. maltophilia (β = -142.62, adjusted P = 0.001) in mothers, and with Muribaculaceae (β = -2702.77, adjusted P = 0.003) in neonates.ConclusionLEA was associated with changes in maternal and neonatal gut microbiota, and future studies are still required to assess their impact on clinical outcomes and explore the mechanisms.

Pregnancy alters many physiological systems, including the maternal gut microbiota. Diet is a key regulator of this system and can alter the host immune system to promote inflammation. Multiple perinatal disorders have been associated with inflammation, maternal metabolic alterations, and gut microbial dysbiosis, including gestational diabetes mellitus, pre-eclampsia, preterm birth, and mood disorders. However, the effects of high-inflammatory diets on the gut microbiota during pregnancy have yet to be fully explored. We aimed to address this gap using a system-based approach to characterize associations among dietary inflammatory potential, a measure of diet quality, and the gut microbiome during pregnancy. Forty-seven pregnant persons were recruited prior to 16 weeks of gestation. Participants completed a food frequency questionnaire (FFQ) and provided fecal samples. Dietary inflammatory potential was assessed using the Dietary Inflammatory Index (DII) from the FFQ data. Fecal samples were analyzed using 16S rRNA amplicon sequencing. Differential taxon abundances with respect to the DII score were identified, and the microbial metabolic potential was predicted using PICRUSt2. Inflammatory diets were associated with decreased vitamin and mineral intake and a dysbiotic gut microbiota structure and predicted metabolism. Gut microbial compositional differences revealed a decrease in short-chain fatty acid producers such as Faecalibacterium, and an increase in predicted vitamin B12 synthesis, methylglyoxal detoxification, galactose metabolism, and multidrug efflux systems in pregnant individuals with increased DII scores. Dietary inflammatory potential was associated with a reduction in the consumption of vitamins and minerals and predicted gut microbiota metabolic dysregulation.

Carbohydrate intolerance, commonly linked to the consumption of lactose, fructose, or sorbitol, affects up to 30% of the population in high-income countries. Although sorbitol intolerance is attributed to malabsorption, the underlying mechanism remains unresolved. Here, we show that a history of antibiotic exposure combined with high fat intake triggered long-lasting sorbitol intolerance in mice by reducing Clostridia abundance, which impaired microbial sorbitol catabolism. The restoration of sorbitol catabolism by inoculation with probiotic Escherichia coli protected mice against sorbitol intolerance but did not restore Clostridia abundance. Inoculation with the butyrate producer Anaerostipes caccae restored a normal Clostridia abundance, which protected mice against sorbitol-induced diarrhea even when the probiotic was cleared. Butyrate restored Clostridia abundance by stimulating epithelial peroxisome proliferator-activated receptor-gamma (PPAR-γ) signaling to restore epithelial hypoxia in the colon. Collectively, these mechanistic insights identify microbial sorbitol catabolism as a potential target for approaches for the diagnosis, treatment, and prevention of sorbitol intolerance.

Randomly barcoded transposon mutant libraries are powerful tools for studying gene function and organization, assessing gene essentiality and pathways, discovering potential therapeutic targets, and understanding the physiology of gut bacteria and their interactions with the host. However, construction of high-quality libraries with uniform representation can be challenging. In this review, we survey various strategies for barcoded library construction, including transposition systems, methods of transposon delivery, optimal library size, and transconjugant selection schemes. We discuss the advantages and limitations of each approach, as well as factors to consider when selecting a strategy. In addition, we highlight experimental and computational advances in arraying condensed libraries from mutant pools. We focus on examples of successful library construction in gut bacteria and their application to gene function studies and drug discovery. Given the need for understanding gene function and organization in gut bacteria, we provide a comprehensive guide for researchers to construct randomly barcoded transposon mutant libraries.

Lacticaseibacillus rhamnosus grx10 (grx10) has shown promising potential in promoting intestinal health as predicted by genomic and metabolomic analyses. Given the increasing prevalence of ulcerative colitis (UC) and the limitations of existing treatments, exploring alternative therapeutic strategies is essential. This study explored the therapeutic effects and underlying mechanisms of grx10 and its derived postbiotic (P‐grx10) in a mouse model of dextran sulfate sodium (DSS)‐induced chronic UC. The intervention with grx10 and P‐grx10 significantly alleviated clinical symptoms and improved biochemical markers in UC mice. These effects included reducing the disease activity index (DAI), improving colon length and histopathological damage, decreasing the secretion of inflammatory cytokines, and preventing the reduction of antioxidant enzymes. Additionally, grx10 and P‐grx10 downregulated key proteins in the Mitogen‐Activated Protein Kinase (MAPK)/myosin light chain kinase (MLCK)/myosin light chain (MLC) pathway, prevented the dissociation of tight junction (TJ) proteins and E‐cadherin, reduced intestinal permeability, and restored the integrity of the intestinal barrier. Furthermore, both grx10 and P‐grx10 modulated the composition and abundance of gut microbiota, helping to maintain intestinal microbiome homeostasis. In conclusion, this study provided evidence regarding the role of grx10 and P‐grx10 in alleviating intestinal barrier dysfunction associated with UC and restoring gut microbiota balance. Notably, P‐grx10 exhibited higher anti‐inflammatory activity and better restoration of intestinal barrier function, whereas the live probiotic grx10 showed a stronger regulatory effect on the gut microbiota. These findings suggest that grx10 and P‐grx10 could serve as promising nutritional adjunct therapies for UC, providing novel insights into the distinct roles of probiotic and its derived postbiotic in UC treatment. [ABSTRACT FROM AUTHOR]

Background: Kalimeris indica (L.) Sch. Bip., (K. indica) is a plant classified under the genus Kalimeris within the Asteraceae family. The herb of K. indica has been historically utilized as a traditional medicine. The consumption of excessive amounts of alcohol represents a lifestyle choice that can induce tissue damage and contribute to the development of various health conditions. Method: The HPLC-MS method was used to reveal the chemical composition of K. indica extract. HepG2 cells were used to test the in vitro oxidative stress. C57BL/6 mice were used to construct the in vivo alcohol-induced liver injury. H/E staining and serum ALT and AST levels were tested to assess the in vivo protective effect of ML (50 and 200 mg/kg). GSH, SOD, and CAT levels along with byproduct MDA levels were used to evaluate the in vivo oxidative stress. Immunohistochemical experiments were used to examine the in vivo Nrf2 and HO-1 levels. 16S rRNA gene-based profiling method was used to test the alteration in gut microbiota. Results: 16 compounds were identified from K. indica extract. K. indica treatment reduced oxidative stress in HepG2 cells treated with 5% alcohol. H/E staining results showed that K. indica (50 and 200 mg/kg) alleviated liver injury caused by alcohol administration, eliciting a similar protective effect to the positive drug silymarin. Serum ALT and AST examination gave a consistent result, showing that ML could restore serum ALT and AST levels in mice treated with alcohol. Furthermore, K. indica could also restore GSH, SOD, CAT, and MDA levels in alcohol-treated mice, showing a potent effect on oxidative stress alleviation. Immunohistochemical experiments indicated that K. indica showed the liver protective effect through Nrf2/HO-1 pathway. 16S rRNA gene-based profiling revealed that alcohol treatment caused the alteration in gut microbiota, while K. indica treatment could result in a significantly richer variety of microbial communities compared to the alcohol group. Conclusion: K. indica (ML) has a protective effect on liver injury caused by alcohol administration. The Nrf2/HO-1 pathway and gut microbiota regulation were involved in the ML-induced liver protection. All the results indicate that K. indica has a potential in the treatment of alcohol-induced liver injury. [ABSTRACT FROM AUTHOR]

This study explores the development of whole-grain sourdough bread with reduced FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) content to offer dietary solutions for individuals with irritable bowel syndrome (IBS). Three sourdough breads were prepared using different lactic acid bacteria (LAB) strains including Lactiplantibacillus plantarum FST1.7 (SD-FST1.7), Lacticaseibacillus paracasei R3 (SD-R3), and Pediococcus pentosaceus RYE106 (SD-RYE106). A control sourdough bread was prepared using baker's yeast (SD-control). In vitro digestion and in vitro colonic fermentation were employed on bread samples with cellulose (negative control) and inulin (positive control), followed by 16S rRNA sequencing and short-chain fatty acid (SCFA) analysis to evaluate the impact on gut microbiota and SCFA levels. Alpha and beta diversity did not reveal any significant differences within the groups following in vitro colonic fermentation (FDR > 0.05). Taxonomic analysis displayed Firmicutes as the predominant phylum across all fecal samples at the end of colonic fermentation. Actinobacteriota was significantly lower in cellulose fermented fecal samples compared to samples fermented with SD-Control (ANCOMBC, FDR = 0.02) and inulin (ANCOMBC, FDR = 0.0001). Fecal samples fermented with inulin had significantly higher Bacteroidota levels compared to those fermented with cellulose (ANCOMBC, FDR =0.002). Acetate levels were higher in fecal samples fermented with SD-FST1.7 compared to those fermented with SD-R3 and SD-RYE106 (p = 0.03 for both). Positive correlations between butyrate and Lachnospira , Agathobacter , and Bifidobacterium were observed, demonstrating the potential of sourdough fermentation to influence gut health and support IBS management. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic, systemic gastrointestinal disorder characterized by episodic inflammation that requires life-long management. Although the etiology of IBD is not fully understood, it is hypothesized to involve a multifaceted interplay among genetic susceptibility, the host immune response, and environmental factors. Previous studies have largely concluded that IBD is associated with this complex interplay; however, more recent evidence underscores the significant role of dietary habits as risk factors for the development of IBD. In this review, we review the molecular mechanisms of high-sugar and high-fat diets in the progression of IBD and specifically address the impacts of these diets on the gut microbiome, immune system regulation, and integrity of the intestinal barrier, thereby highlighting their roles in the pathogenesis and exacerbation of IBD. [ABSTRACT FROM AUTHOR]

Background: Liver disease is among the top ten causes of death globally. With studies suggesting a link between gut microbiota (GM) and liver disease. Method: We selected summary statistics data from the largest available whole-genome association study (n = 13,266) of GM by the MiBioGen consortium as the exposure, and obtained liver disease-related data from IEU Open GWAS and The NHGRI-EBI GWAS Catalog. A two-sample Mendelian Randomization (MR) analysis employing various methods, to establish the causal relationship between GM and five liver diseases. Meanwhile, single-cell RNA sequencing data were used to examine Prevotella-related genes expression under healthy and disease liver. Results: The IVW analysis indicate a causal relationship between GM and liver diseases, with Prevotella exhibiting a protective effect in all five liver diseases: Alcoholic liver disease (OR:0.81,95% confidence interval:0.66-1.00, P IVW = 0.0494); Cirrhosis (OR: 0.85,95% confidence interval: 0.73-0.99, P IVW = 0.0397); Hepatic failure, not elsewhere classified (OR:0.60,95% confidence interval:0.37-0.95, P IVW = 0.0305); Benign neoplasm:Liver (OR:0.39,95% confidence interval:0.2-0.75, P IVW = 0.0046); Malignant neoplasm of liver, primary (OR:0.41, 95% confidence interval:0.18-0.93, P IVW = 0.0334). The single-cell results suggest differential expression of Prevotella-related genes between liver disease patients and healthy individuals. Conclusion: Our MR results show a causal relationship between the GM and liver disease. Prevotella displays a notable protective effect. This finding may enhance the precision of GM-based therapies and offer new insights for clinical research. [ABSTRACT FROM AUTHOR]

Introduction: In recent years, an increasing body of research has illustrated a strong correlation between gut microbiota and depression. However, there has yet to be a comprehensive discussion or summary of the latest advancements and trends in this field. Methods: We retrieved research articles focused on gut microbiota and depression through the WOS database from 2020 to 2024, using visual text analysis tools such as CiteSpace and VOSviewer. Results: The literature on the relationship between gut microbiota and depression surged from 396 papers in 2020 to 711 by 2024. During this period, the journal with the highest publication rate was Nutrients. China led the countries in contributions, while University College Cork topped the institutions. Kenji Hashimoto emerged as the most prolific author. The most cited paper was authored by Cryan JF et al., published in 2019 in Physiol Rev. The keywords "gut microbiota," "depression," and "anxiety" appeared most frequently, while recent years saw explosive increases in terms such as "growth performance," "receptors," "depression-like phenotypes," "stress response," "gastrointestinal symptoms," "reliability," and "neurogenesis." Discussion: Our article displayed the overview of the relationship between the gut microbiome and depression from 2020 to 2024 using bibliometric methods, providing perspectives and research hotspots for studies exploring the correlation between the gut microbiome and depression. [ABSTRACT FROM AUTHOR]

Background: Obesity has become a global pandemic, marked by significant shifts in both the homeostatic and hedonic/reward aspects of food consumption. While the precise causes are still under investigation, recent studies have identified the role of gut microbes in dysregulating the reward system within the context of obesity. Unravelling these gut–brain connections is crucial for developing effective interventions against eating and metabolic disorders, particularly in the context of obesity. This study explores the causal role of LPS, as a key relay of microbiota component-induced neuroinflammation in the dysregulation of the reward system following exposure to high-fat diet (HFD). Methods: Through a series of behavioural paradigms related to food-reward events and the use of pharmacological agents targeting the dopamine circuit, we investigated the mechanisms associated with the development of reward dysregulation during HFD-feeding in male mice. A Toll-like receptor 4 (TLR4) full knockout model and intraventricular lipopolysaccharide (LPS) diffusion at low doses, which mimics the obesity-associated neuroinflammatory phenotype, were used to investigate the causal roles of gut microbiota-derived components in neuroinflammation and reward dysregulation. Results: Our study revealed that short term exposure to HFD (24 h) tended to affect food-seeking behaviour, and this effect became significant after 1 week of HFD. Moreover, we found that deletion of TLR4 induced a partial protection against HFD-induced neuroinflammation and reward dysregulation. Finally, chronic brain diffusion of LPS recapitulated, at least in part, HFD-induced molecular and behavioural dysfunctions within the reward system. Conclusions: These findings highlight a link between the neuroinflammatory processes triggered by the gut microbiota components LPS and the dysregulation of the reward system during HFD-induced obesity through the TLR4 pathway, thus paving the way for future therapeutic approaches. [ABSTRACT FROM AUTHOR]

Targeting specific gut microbiota (GM) species to prevent and treat acute upper respiratory tract infection (AURTI) has attracted researchers' attention, but the relationship between the two is unclear. Based on the summary data from genome-wide association studies (GWAS) on GM and five types of AURTIs (acute nasopharyngitis (common cold), acute pharyngitis, acute sinusitis, acute upper respiratory infections, and acute upper respiratory infections of multiple and unspecified sites), we performed two-sample bidirectional Mendelian randomization (MR) to assess the causal relationship. Through inverse variance weighting (IVW) method, we found that 33 potential microbial taxa can influence the occurrence of AURTI. Sensitivity analysis showed no potential horizontal pleiotropy and heterogeneity bias. We further employed multivariable Mendelian randomization to investigate the impact of potential interference factors on the significant associations previously identified, considering aspects such as comorbidities associated with AURTI, seasonal variations, pathogen specificity, and history of antibiotic allergies. Ultimately, 11 microbial taxa remained significantly associated. This study provides robust evidence for a causal relationship between GM and five types of AURTIs, thereby offering a foundation for the development of microbiota-targeted therapies and related probiotic interventions aimed at AURTI. [ABSTRACT FROM AUTHOR]

Background: The prevalence of metabolic syndrome is on the rise globally. Understanding the etiology and discovering potential treatment target have become a priority. Observational data have linked gut microbiota with metabolic syndrome and its comprising traits. However, whether these relations underlie causal effects remains unclear. Methods: Using Inver Variance Weighted (IVW) as primary analysis method, we performed two-sample Mendelian Randomization (MR) analyses to explore the causal relationship between gut microbiota and metabolic syndrome with its comprising traits. Methods including MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), Weighted Mode, and Weighted Median were chosen for additional MR analysis to test the robustness of MR results. Cochran's IVW Q test and leave-one-out IVW analysis tested the heterogeneity among instrumental variables (IVs). Steiger filtering was utilized to exclude all IVs with reverse causality. Genome-wide association study (GWAS) data used in this study were all from the largest respective GWAS studies available. Results: Out of 1172 tests, a total of 16 associations with evidence of causality were identified after sensitivity analyses, but only 3 remained after multiple testing correction. Class Melainabacteria (β = 0.02, adjusted P = 0.01) with affiliated order Gastranaerophilales (β = 0.02, adjusted P = 1.20*10− 3) and genus Eubacterium hallii (β = 0.03, adjusted P = 0.03) showed a positive effect on abdominal obesity. All effect sizes were small (abs(β) < 0.1). All causal relationships identified were unidirectional. Conclusions: Given the study's limitations, we found little evidence supporting a large causal effect, i.e. absolute effect size > 0.1, of gut microbial taxa abundance on metabolic syndrome and its comprising traits. This study also suggests that previously reported associations between gut microbiota and metabolic syndrome with its comprising traits may not necessarily lead to causal relations. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

ABSTRACT Gut microbiota regulate multiple aspects of host health, including metabolism and the development of the immune system. However, we still know relatively little about how the gut microbiota influences host responses to parasitism in wild organisms, particularly whether host‐microbiota interactions contribute to variation in parasitism across host species. The goal of this study was to determine the role of gut microbiota in shaping how birds respond to nest parasites and investigate whether this relationship varies between host species. Both eastern bluebirds (Sialia sialis) and tree swallows (Tachycineta bicolor) are parasitized by blow flies (Protocalliphora sialia), for which larval flies feed on nestlings' blood. We experimentally manipulated the gut microbiota of nestling bluebirds and tree swallows by dosing nestlings with an oral antibiotic or sterile water as a control. We then quantified nestling physiology (haemoglobin, glucose, parasite‐specific IgY antibody levels), body morphometrics, and survival until fledging, as well as blow fly abundance and size. An experimental disruption of nestling gut microbiota increased parasite abundance in tree swallows, but decreased parasite abundance in bluebirds, which suggests that the disruption has opposing effects on resistance across host species. Furthermore, experimental treatment delayed parasite development and had variable effects on nestling body morphometrics and physiology across the two host species. Together, these results suggest that gut microbiota contribute to host differences in resistance to blow flies and can influence host–parasite interactions. [ABSTRACT FROM AUTHOR]

Background: Mucosal healing is the therapeutic target for ulcerative colitis (UC). While amino acids (AAs) and the gut microbiota are known to be involved in the pathogenesis of UC, their specific roles in mucosal healing have not been fully defined. Objectives: To longitudinally assess the changes in AA concentrations and the gut microbiota composition in the context of mucosal healing in UC patients, with the aim of identifying new biomarkers with predictive value for mucosal healing in UC patients and providing a new theoretical basis for dietary therapy. Methods: A total of 15 UC patients with infliximab-induced mucosal healing were enrolled. Serum and fecal AA concentrations before and after mucosal healing were determined via targeted metabolomics. A receiver operating characteristic (ROC) curve was plotted to evaluate the value of different AAs in predicting mucosal healing in UC patients. The changes in the composition of the fecal gut microbiota were analyzed via metagenomics, and bioinformatics was used to analyze the functional genes and metabolic pathways associated with different bacterial species. Spearman correlation analyses of fecal AAs with significantly different concentrations and the differentially abundant bacterial species before and after mucosal healing were performed. Results: 1. The fecal concentrations of alanine, aspartic acid, glutamic acid, glutamine, glycine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine and valine were significantly decreased after mucosal healing. The serum concentrations of alanine, cysteine and valine significantly increased, whereas that of aspartic acid significantly decreased. Glutamic acid, leucine, lysine, methionine and threonine could accurately predict mucosal healing in UC patients, and the area under the curve (AUC) was > 0.9. After combining the 5 amino acids, the AUC reached 0.96. 2. There were significant differences in the gut microbiota composition before and after mucosal healing in UC, characterized by an increase in the abundance of beneficial microbiota (Faecalibacterium prausnitzii and Bacteroides fragilis) and a decrease in the abundance of harmful microbiota (Enterococcus faecalis). LEfSe analysis identified 57 species that could predict mucosal healing, and the AUC was 0.7846. 3. Amino acid metabolic pathways were enriched in samples after mucosal healing, was associated with the abundance of multiple species, such as Faecalibacterium prausnitzi, Bacteroides fragilis, Bacteroides vulgatus and Alistipes putredinis. 4. The fecal concentrations of several AAs were negatively correlated with the abundance of a variety of beneficial strains, such as Bacteroides fragilis, uncultured Clostridium sp., Firmicutes bacterium CAG:103, Adlercreutzia equolifaciens, Coprococcus comes and positively correlated with the abundance of several harmful strains, such as Citrobacter freundii, Enterococcus faecalis, Klebsiella aerogenes, Salmonella enterica. Conclusion: Altered concentrations of amino acids and their associations with the gut microbiota are implicated in the mucosal healing of UC patients and can serve as noninvasive diagnostic biomarkers. [ABSTRACT FROM AUTHOR]

Carvacrol and thymol (CAT) have been widely recognized for their antimicrobial and anti‐inflammatory properties, yet their specific effects on colitis and the mechanisms involved remain insufficiently understood. This study establishes a causative link between CAT administration and colitis mitigation, primarily through the enhancement of Bifidobacterium pseudolongum abundance in the colon. This increase promotes the production of secondary bile acids, particularly hyodeoxycholic acid (HDCA) and 12‐ketodeoxycholic acid (12‐KCAC), which exert anti‐inflammatory effects. Notably, CAT does not alleviate colitis symptoms in germ‐free mice, indicating the necessity of gut microbiota. This research uncovers a novel regulatory mechanism where HDCA and 12‐KCAC inhibit colonic inflammation by reducing the expression of transmembrane guanylate cyclase 1A in the colonic epithelium. This downregulation elevates intracellular Ca2+ and cGMP levels, activating protein kinase G (PKG). Activated PKG subsequently suppresses the mTOR signaling pathway, thereby ameliorating dextran sulfate sodium (DSS)‐induced colonic damage. These findings highlight potential metabolites and therapeutic targets for preventing and treating colitis. Bifidobacterium pseudolongum, HDCA, and 12‐KCAC emerge as promising candidates for therapeutic interventions in colitis and related disorders characterized by impaired tight junction function. [ABSTRACT FROM AUTHOR]

Background: Research has demonstrated that obesity may be associated with rheumatoid arthritis (RA). In addition, Dysbiosis of intestinal microbiota and their metabolites has been linked to the occurrence and development of RA and obesity. However, the mechanism by which obesity affects RA remains unclear.In this study, we explored the impact of high fat diet(HFD) on collagen-induced arthritis (CIA) rats and revealed its mechanisms based on gut microbiota and metabolomics. Methods: Based on diet and modeling, rats were divided into normal group (Con), CIA model group, HFD group (HFD), and HFD + CIA group (HCIA). The effect of HFD on arthritis in CIA rats were investigated based on the arthritis index (AI), weight, blood lipid levels, and inflammatory cytokines. Moreover, HE staining and micro-CT were performed to evaluated the effect of HFD on the pathology of joints and synovial tissues in CIA rats.16S rRNA amplicon sequencing and liquid chromatography-mass spectrometry (LC–MS) were employed to explore changes in gut microbiota and short-chain fatty acids (SCFAs). Results: The AI scores, inflammatory cytokines and bone destruction parameters in the HCIA group were significantly higher than those in the other three groups. The results of 16S rRNA amplicon sequencing and metabolomics showed that compared with the other three groups, the expression of g_Muribaculaceae and butyric acid were reduced in the HCIA group. Spearman and linear correlation analyses revealed a positive correlation between g_Muribaculaceae abundance and butyric acid levels. Conclusions: HFD stimulated butyric acid metabolism dysbiosis, altered microbiota, and aggravated inflammatory response in CIA rats. [ABSTRACT FROM AUTHOR]

Background: Individuals with type 1 diabetes are at increased risk of accelerated atherosclerosis, causing coronary artery disease (CAD). The underlying mechanisms remain unclear, but new theories proposed are damage of gut mucosa causing leakage and translocation of gut microbiota products into the circulation, leading to inflammatory responses and atherosclerosis. We therefore aimed to study the associations between gut related inflammatory biomarkers and coronary atherosclerosis in individuals with long-term type 1 diabetes. Methods: In this cross-sectional, controlled study of 102 participants with type 1 diabetes and 63 control subjects, we measured circulating levels of intestinal fatty acid binding protein (I-FABP), soluble cluster of differentiation 14 (sCD14), lipopolysaccharide binding protein (LBP) and interleukin 18 (IL-18) by enzyme-linked immunosorbent assay (ELISA), and further gene expression of CD14 and toll-like receptor 4 (TLR4) by real time PCR in circulating leukocytes and peripheral blood mononuclear cells (PBMCs). The participants had either established coronary heart disease (CHD) or underwent computed tomography coronary angiography (CTCA) to assess for coronary atherosclerosis, including total, calcified and soft/mixed plaque volumes. Results: In the diabetes group, the levels of I-FABP were significantly higher in participants with established CHD or significant stenosis on CTCA compared to the participants with normal arteries or non-significant stenosis, with median 1.67 ng/ml (interquartile range [IQR] 1.02–2.32) vs. median 1.09 ng/ml (IQR 0.82–1.58), p = 0.003. I-FABP was associated with significant coronary artery stenosis by CTCA (> 50%) or previously established CHD in the adjusted analysis (odds ratio [OR] = 2.32, 95% confidence interval [CI]: 1.09–4.95; p = 0.029). The levels of I-FABP correlated also to total coronary plaque volume (r = 0.22, p < 0.05). This association remained significant after adjusting for age, sex, persistent albuminuria, eGFR, statin treatment, diabetes duration and mean time-weighted variables; HbA1c, LDL-cholesterol and systolic blood pressure (OR = 1.97, 95% CI: 1.28–3.01; p = 0.002). Conclusions: In this cohort of individuals with long-term type 1 diabetes I-FABP associated significantly with coronary artery stenosis, suggesting a potential role of gut mucosa damage in the process of atherosclerosis in type 1 diabetes. [ABSTRACT FROM AUTHOR]

Background: The Coronavirus disease 2019 (COVID-19) pandemic has emerged as a global health crisis, with clinical manifestations including those suggesting injury to various organs such as the ovaries, which implies that it extends beyond respiratory infections. Changes in gut microbiota may exhibit correlations with the mechanisms and stages of severity in COVID-19, as well as a link with sex hormones, embryo development, and pregnancy. Controlled ovarian stimulation (COS) is used to induce the development of multiple high-quality follicles during in vitro fertilization (IVF). Our research aimed to investigate whether patients infected with COVID-19 have altered gut microbiota compositions that would affect the outcomes of COS. Methods: Twenty-one healthy females and seventeen patients with COVID-19 were enrolled. Samples were sequenced for gut microbiota identification through 16 S rRNA V3-V4 region, including species annotation, community diversity, and community functions. Results: No significant differences were found between the groups in terms of in IVF cycle outcomes and laboratory parameters. Patients with COVID-19 and healthy women showed no significant difference in the total number of available blastocyst embryos. Furthermore, the gut microbiota alpha diversity index in the COVID-19 group were markedly reduced compared to those of healthy females. Comparing the COVID-19 group to the controls, the gut microbiota dysbiosis decreased levels of Ruminococcus, and Agathobater, and elevated levels of Achromobacter and Raistonia. Finally, we identified a series of microbial functional characteristics, including membrane transport and carbohydrate metabolism, that exhibited significant disparities between the two groups. Conclusions: Patients in the COVID-19 group exhibited significant disparities in the gut microbiota composition compared to the healthy women during COS. However, the IVF outcomes did not show any significant differences between the two groups. Collectively, our speculation suggests that SARS-COV-2 infection may alter the gut microbiota without impacting IVF outcomes. [ABSTRACT FROM AUTHOR]

Immunotherapy is a novel treatment approach for malignant tumors, which has opened a new journey of anti-tumor therapy. Although some patients will show a positive response to immunotherapy, unfortunately, most patients and cancer types do not achieve an ideal response to immunotherapy. Therefore, it is urgent to search for the pathogenesis of sensitized immunotherapy. This review indicates that Fusobacterium nucleatum, Coprobacillus cateniformis, Akkermansia muciniphila, Bifidobacterium, among others, as well as intestinal microbial metabolites are closely associated with resistance to anti-tumor immunotherapy. While natural products of pectin, inulin, jujube, anthocyanins, ginseng polysaccharides, diosgenin, camu-camu, and Inonotus hispidus (Bull).Fr. P. Karst, Icariside I, Safflower yellow, Ganoderma lucidum, and Ginsenoside Rk3, and other Chinese native medicinal compound prescriptions to boost their efficacy of anti-tumor immunotherapy through the regulation of microbiota and microbiota metabolites. However, current research mainly focuses on intestinal, liver, and lung cancer. In the future, natural products could be a viable option for treating malignant tumors, such as pancreatic, esophageal, and gastric malignancies, via sensitizing immunotherapy. Besides, the application characteristics of different types, sources and efficacy of natural products in different immune resistance scenarios also need to be further clarified through the development of future immunotherapy-related studies. [ABSTRACT FROM AUTHOR]

Recent studies have shown that old, traditionally managed semi‐natural grasslands (SNGs) harbour specific plant assemblages characterized by high species richness, diversity, evenness and a great abundance and diversity of floral resources. As nectar and pollen from many of these plants contain a multitude of favourable phytochemical compounds, we hypothesized that pollinator health and survival would improve in old, species‐rich hay SNGs compared to younger SNGs. We monitored experimental colonies of bumblebees placed in hay SNGs of different ages. The survival of bumblebees increased with grassland age, thus they lived longer and produced more workers in the old SNGs. The abundance of actinomorphic flowers (with radial symmetry) increased with the age of the SNGs and was positively correlated with the body size, body mass and lipid reserves of the bumblebees. The taxonomic composition of gut microbiota changed during the experiment, with a significant decrease of core taxa Bombiscardovia and Bifidobacterium in young SNGs, while the abundance of Bombilactobacillus increased in old SNGs. At the end of the experiment, the bumblebees of young SNGs hosted lower abundances of Gilliamella than those of old SNGs. In old SNGs, there was a positive relationship between floral richness and the abundance of six taxa, including the three core taxa Bombiscardovia, Bifidobacterium and Snodgrassella. Microbiota α‐diversity decreased and microbiota β‐diversity increased over time in young SNGs, while both remained stable in old SNGs. Both deterministic and stochastic processes acting simultaneously in bumblebee microbiomes within young SNGs seemed to explain these changes. Compared to old forests, very little attention has been paid to old, species‐rich grasslands. Considering their importance for pollinator health, as well as their high ecological and cultural values, it is crucial that the rare and endangered old, species‐rich hay SNGs are protected. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Infertility is a condition where a male or female is unable to achieve pregnancy through at least 1 year of regular, unprotected sexual intercourse. There are several known causes and risk factors associated with infertility. The gut microbiota is a complex community of trillions of microorganisms living in the gut. Due to modern lifestyle changes, such as dietary habits, physical inactivity, and increasing antibiotic use, the diversity and composition of these microbes may change in a detrimental manner. Dysbiosis or an imbalance of the gut microbiota compared to a normal composition can lead to various abnormalities, such as obesity, Alzheimer's, metabolic disorders, and infertility. This review will cover the factors influencing gut microbiota composition, the mechanisms by which gut microbiota contributes to infertility in men and women, the effects of gut microbiota on problems that may arise during pregnancy, and therapeutic methods for diseases caused by dysbiosis of the gut microbiota. [ABSTRACT FROM AUTHOR]

Phenolic compounds show promise in treating obesity and enhancing intestinal health. This systematic review addressed the following question: "What are the effects of polyphenols on intestinal health in preclinical studies with diet-induced obesity?". The review followed PRISMA guidelines and was registered in PROSPERO(CRD42021262445). Studies published until April 2024 were selected from Medline(PubMed), Web of Science, Scopus, Embase, and ScienceDirect using terms related to polyphenols, obesity, and microbiota in rats and mice. Thirty papers meeting PICOS criteria were included. Bias risk was assessed with the SYRCLE tool, yielding scores between 4.5 and 7.0 out of 10. Findings indicated that 22 phenolic compounds improved gut microbiota diversity, reduced the Firmicutes/Bacteroides ratio, and modulated microbiota at various taxonomic levels. They also increased short-chain fatty acids, tight-junction expression, enhanced intestinal morphology, and reduced endotoxemia and inflammatory cytokines. These results suggest phenolic compounds may help treat obesity by modifying the microbiota and improving intestinal health. However, further research is needed to standardize data and facilitate meta-analyses. [ABSTRACT FROM AUTHOR]

Existence of Trimethylamine N-oxide (TMAO) and trimethylamine (TMA) are well recognized through our multiple human activities. Most of them are derived from quaternary ammoniums widely distributed in natural products, which have N-trimethyl moiety. There could also be some inhibitors to reduce their yield. TMAO is known as a representative component in seafood and is recently gaining large attention. TMAO is formed mostly from choline and carnitine in animal products by mediating gut microbes and host monooxygenase in the human body. Teleost tilapia also has a similar mechanism well mediating choline. In marine habitants, TMAO is utilized as an osmolyte. In human, however, the endogenous TMAO is reported to be associated with a risk of cardiovascular events. During the organic evolution, marine creatures could develop utilizing TMAO while avoiding risks. This article, therefore, reviews and characterize the TMAO/TMA having different profiles, and consider the possible inhibitors preventing undesired metabolisms, to try to find clues of the TMAO subjects and consider possibilities and prospects. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota has a profound effect on immunity and metabolic status of the host, which has increasingly attracted research communities. However, the intrinsic mechanism underlying the interplay among these three aspects remains unclear. Results: Different immune states were established via shaping the population structure of gut microbiota with antibacterial agents. The gut microbiota population structures altered with the subtherapeutic level of antibacterial agents facilitated growth phenotype in both piglets and infant mice. Notably, increased colonization of Prevotella copri was observed in the intestinal microbiota, which shifted the immune balance from a CD4+ T cell-dominated population toward a T helper 2 cell (Th2) phenotype, accompanied by a significant elevation of interleukin-13 (IL-13) levels in the portal vein, which was found to display a strong positive correlation with hepatic insulin-like growth factor-1 (IGF-1) levels. Subsequent investigations unveiled that gut-derived IL-13 stimulated the production of hepatic IGF-1 by activating the IL-13R/Jak2/Stat6 pathway in vitro. The IGF-1 levels were increased in the muscles, leading to an upregulation of and resulted the increased genes associated with related to myofibrillar synthesis and differentiation, which ultimately improving the growth phenotype. Conclusions: Our findings highlight the modification of gut immunity states as a central strategy for increasing anabolism of the host, which has significant implications for addressing human undernutrition/stunting, sarcopenia, obesity and related comorbidities. 6McQiT2YyFVHMbM3Aew6C8 Video Abstract [ABSTRACT FROM AUTHOR]

Introduction: Numerous studies have reported alterations in the composition of gut microbiota in patients with acute ischemic stroke (AIS), with changes becoming more pronounced as the disease progresses. However, the association between the progression of transient ischemic attack (TIA) and AIS remains unclear. This study aims to elucidate the microbial differences among TIA, AIS, and healthy controls (HC) while exploring the associations between disease progression and gut microbiota. Methods: Fecal samples were collected from acute TIA patients (n = 28), AIS patients (n = 235), and healthy controls (n = 75) and analyzed using 16 s rRNA gene sequencing. We determined characteristic microbiota through linear discriminant analysis effect size and used the receiver operating characteristic (ROC) curve to assess their predictive value as diagnostic biomarkers. Results: Our results showed significant gut microbial differences among the TIA, AIS, and HC groups. Patients with AIS exhibited higher abundances of Lactobacillus and Streptococcus, along with lower abundances of Butyricicoccaceae and Lachnospiraceae _UCG-004. Further analysis revealed that the abundance of characteristic bacteria, such as Lactobacillus and Streptococcus , was negatively correlated with HDL levels, while Lactobacillus was positively correlated with risk factors such as homocysteine (Hcy). In contrast, the abundance of Lachnospiraceae _UCG-004 was negatively correlated with both Hcy and D-dimer levels. ROC models based on the characteristic bacteria Streptococcus and Lactobacillus effectively distinguished TIA from AIS, yielding areas under the curve of 0.699 and 0.626, respectively. Conclusion: We identified distinct changes in gut bacteria associated with the progression from TIA to AIS and highlighted specific characteristic bacteria as predictive biomarkers. Overall, our findings may promote the development of microbiome-oriented diagnostic methods for the early detection of AIS. [ABSTRACT FROM AUTHOR]

Background: We employed Mendelian randomization (MR) to investigate the causal relationship between the gut microbiota and lymphoid leukemia, further exploring the causal relationships among immune cells, lymphoid leukemia, and potential metabolic mediators. Methods: We utilized data from the largest genome-wide association studies to date, encompassing 418 species of gut microbiota, 713 types of immune cells, and 1,400 serum metabolites as exposures. Summary statistics for lymphoid leukemia, acute lymphocytic leukemia (ALL), and chronic lymphocytic leukemia (CLL) were obtained from the FinnGen database. We performed bidirectional Mendelian analyses to explore the causal relationships among the gut microbiota, immune cells, serum metabolites, and lymphoid leukemia. Additionally, we conducted a two-step mediation analysis to identify potential intermediary metabolites between immune cells and lymphoid leukemia. Results: Several gut microbiota were found to have causal relationships with lymphoid leukemia, ALL, and CLL, particularly within the Firmicutes and Bacteroidetes phyla. In the two-step MR analysis, various steroid hormone metabolites (such as DHEAS, pregnenolone sulfateprogestogen derivatives, and androstenediol-related compounds) were identified as potential intermediary metabolites between lymphoid leukemia and immune cells. In ALL, the causal relationship between 1-palmitoyl-2-docosahexaenoyl-GPE (16:0/22:6) and ALL was mediated by CD62L-plasmacytoid DC%DC (mediated proportion=-2.84%, P =0.020). In CLL, the causal relationship between N6,n6,n6-trimethyllysine and CLL was mediated by HLA DR+ CD8br AC (mediated proportion=4.07%, P =0.021). Conclusion: This MR study provides evidence supporting specific causal relationships between the gut microbiota and lymphoid leukemia, as well as between certain immune cells and lymphoid leukemia with potential intermediary metabolites. [ABSTRACT FROM AUTHOR]

Hyperuricemia (HUA) is the presence of excessive uric acid (UA) in blood, which leads to an increased risk of chronic kidney disease and gout. Probiotics have the potential effect of alleviating HUA. The purpose of this study was to screen probiotics with UA-lowering activity and explore the underlying mechanism. The UA-lowering activity of 20 lactic acid bacteria strains was investigated in vitro , and the effect of candidate probiotics on UA metabolism was evaluated using the HUA Balb/c mouse model. The results showed that Lactobacillus paracasei X11 had excellent UA-lowering activity in vitro , which could degrade nucleotides and nucleosides completely within 30 min, and the degradation rates of purine and trioxypurine could reach 83.25% and 80.42%, respectively. In addition, oral administration of L. paracasei X11 could reduce serum UA by 52.45% and inhibit renal proinflammatory cytokine IL-1β by 50.69%, regulating adenosine deaminase (ADA), xanthine oxidase (XOD), and transporter expression (GLUT9, NPT1, and URAT1) to a normal level. Moreover, it could restore the ratio of Bacteroidetes to Firmicutes (Bac/Firm ratio) and showed a positive effect on the recovery of the intestinal microbiota. These findings provided fundamental information about the UA-lowering properties of probiotics, which suggested that L. paracasei X11 had the potential to be developed as a novel probiotic strain to ameliorate HUA. [ABSTRACT FROM AUTHOR]

Introduction: Allergen-specific immunotherapy (AIT) induces long-term immune tolerance to allergens and is effective for treating allergic rhinitis (AR). However, the impact of sublingual immunotherapy (SLIT) on gut microbiota from AR patients and its correlation with treatment efficacy remains unclear. Methods: In the present study, we enrolled 24 AR patients sensitized to Dermatophagoides farinae (Der-f) and 6 healthy donors (HD). All AR patients received SLIT treatment using standardized Der-f drops. Stool samples were collected from AR patients before treatment, and 1- and 3-months post-treatment, as well as from HD, for metagenomic sequencing analysis. Results: AR patients had significantly lower richness and diversity in gut microbiota compared to HD, with notable alterations in composition and function. Besides, three months post-SLIT treatment, significant changes in gut microbiota composition at the genus and species levels were observed in AR patients. Streptococcus parasanguinis_B and Streptococcus parasanguinis , which were significantly lower in AR patients compared to HD, increased notably after three months of treatment. LEfSe analysis identified these species as markers distinguishing HD from AR patients and AR patients pre- from post-SLIT treatment. Furthermore, changes in the relative abundance of S. parasanguinis_B were negatively correlated with changes in VAS scores but positively correlated with changes in RCAT scores, suggesting a positive correlation with effective SLIT treatment. Discussion: SLIT treatment significantly alters the gut microbiota of AR patients, with S. parasanguinis_B potentially linked to its effectiveness. This study offers insights into SLIT mechanisms and suggests that specific strains may serve as biomarkers for predicting SLIT efficacy and as modulators for improving SLIT efficacy. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota and derived metabolites play a key role in regulating host physiology. Diet is identified as a key regulatory factor of the microbiota composition and, potentially, of subsequent functionalities. Demonstrating the role of diet may be complex as most human studies are cross-sectional and dietary intervention is often accompanied by hygienic changes. The objective of the present study was to investigate the impact of an industrial diet on the modulation of the microbiota and targeted functionalities using a canine "natural" model. Results: We carried out a controlled dietary trial in a cohort of Tunisian semi-stray dogs. We made a transition from a natural diet to an industrial kibble diet and monitored the composition of the fecal microbiota, the concentration of short-chain fatty acids (SCFA) and bile acids (BAs), and protease activities. We demonstrated that dietary change significantly decreased fecal primary bile acids levels and protease activities. Interestingly, correlation analyses demonstrated that variation of specific microbial genera were associated with modulated physiological parameters. Conclusions: Our study reveals that an industrial diet induces beneficial changes in microbial composition and functions characterised by increased diversity, synthesis of SCFA and secondary bile acids production, stressing the key role of the diet-microbiota-dog crosstalk. [ABSTRACT FROM AUTHOR]

Objective: This study aims to clearly define the effects of Banxia-Yiyiren on the gut microbiota and its metabolites in a para-chlorophenylalanine-induced insomnia model and the possible underlying mechanisms involved. Materials and methods: We employed 16S ribosomal ribonucleic acid (rRNA) gene sequencing combined with metabonomic analysis to explore the mutual effects of the PCPA-induced insomnia model and the gut microbiota and the intrinsic regulatory mechanism of Banxia-Yiyiren on the gut microbiota and metabolites in the PCPA-induced insomnia model. Results: Banxia-Yiyiren was identified by mass spectrometry to include amino acids, small peptides, nucleotides, organic acids, flavonoids, fatty acids, lipids, and other main compound components. The elevated plus maze (EPM) test results revealed that high-dose Banxia-Yiyiren may increase willingness to explore by improving anxiety-like symptoms caused by insomnia. Through 16S rRNA gene sequencing, at the phylum level, compared with those in G1, the relative abundances of Bacteroidota and Proteobacteria in G2 increased, whereas the relative abundance of Firmicutes decreased. At the genus level, compared with those in G1, the relative abundances of Prevotella_9 , Prevotella , Ralstonia , Escherichia-Shigella , and UCG-005 in G2 increased, whereas the relative abundances of Lactobacillus , Ligilactobacillus , Alloprevotella , Blautia , and Prevotellaceae_NK3B31_group decreased. The metabolomics analysis results revealed 1,574 metabolites, 36.48% of which were classified as lipids and lipid-like molecules, 20.76% as organic acids and their derivatives, and 13.36% as organic heterocyclic compounds. The correlation between the top 20 differentially abundant metabolites in the G1–G2 groups was greater than that between the G3–G2 and G6–G2 groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the main differentially abundant metabolites in each group were significantly enriched in various pathways, such as amino acid metabolism, adenosine triphosphate (ATP)-binding cassette (ABC) transporters, protein digestion, and absorption. Additionally, there was a significant Pearson correlation between the genus-level differences in the gut microbiota and the differentially abundant metabolites among the G1–G2, G3–G2, and G6–G2 groups. Conclusion: This study preliminarily verified that the PCPA-induced insomnia model is closely related to gut microbial metabolism and microecological disorders, and for the first time, we confirmed that Banxia-Yiyiren can act on the gut microbiota of PCPA-induced insomnia model rats and alleviate insomnia and anxiety by regulating the species, structure, abundance, and metabolites of the gut microbiota. [ABSTRACT FROM AUTHOR]

Introduction: Alterations in cognitive performance are associated with inadequate nutritional states and diet composition. Prebiotics, such as inulin, are substances that can modulate the gut microbiome and, consequently, brain function by producing metabolites such as short-chain fatty acids (SCFAs). This study aimed to evaluate the effect of supplementation with inulin on cognitive flexibility, body composition, and gut microbiota in a murine model exposed to a high-fat (HF) diet. Methods: CD1 mice were divided into five groups: control fed a standard diet (C), high-fat diet (HF), inulin (I), high-fat diet with inulin (HFI), and manipulation control (M). Dietary supplementation was administered for 6 weeks. Cognitive flexibility was assessed using the Attentional Set-Shifting Test (AST). In addition, body composition was measured via electrical bioimpedance and adipose tissue compartments of each mouse were removed and weighed. Finally, gut microbiota metataxonomic was analyzed through metataxonomic bacterial 16S rRNA sequencing. Results: We observed that HF group required more AST trials than the C, HFI, and I groups in the compound discrimination (CD) and extra-dimensional (ED) stages. Notably, the HFI group required fewer trials than the HF group in the ED stage (p = 0.0187). No significant differences in overall body composition were observed between the groups. However, the percentage of gonadal and peritoneal adipose tissue was significantly higher in the HF and I groups compared to the C group. Statistically significant differences in alpha diversity for gut microbiota were observed using the Shannon, Simpson, and Chao1 indices. The I group showed a decrease in bacterial diversity compared to the HF group. While no differences were observed between groups in the phyla Bacillota and Bacteroidotes, Clostridium bacteria represented a lower proportion of sequences in the I group compared to the C group. Additionally, Lactobacillus represented a lower proportion of sequences in the HF group compared to the C and I groups. Discussion: These findings suggest that supplementation with inulin could be a useful approach to mitigate the negative effects of an HF diet on cognitive flexibility and modulate gut microbiota composition. [ABSTRACT FROM AUTHOR]

Grey mullet (Mugil cephalus) aquaculture is economically vital due to the high value of its roe. However, it faces significant risks from disease outbreaks, particularly from Nocardia seriolae. Current reliance on antibiotics has drawbacks, highlighting the potential of probiotics as a promising alternative. Despite this, no studies have focused on the effects and mechanisms of probiotics in disease prevention and treatment in grey mullet. This study, therefore, investigates the efficacy of probiotics in enhancing disease resistance and promoting growth in grey mullet. Three strains of probiotics, Lacticaseibacillus rhamnosus FS3051, Limosilactobacillus reuteri FS3052, and Bacillus subtilis natto NTU-18, were selected to evaluate their anti-N. seriolae activity and hydrolytic enzyme secretion in vitro. Then, 144 grey mullet were randomly divided into four groups: control, L. rhamnosus FS3051, L. reuteri FS3052, and B. subtilis natto NTU-18. After being fed the corresponding diet for 28 days, fish were measured for immune gene expression and short-term growth followed by challenge of N. seriolae. Survival rates were recorded for 35 days post challenge. Additionally, the gut microbiota of the control and probiotic groups with effects on both growth and protection against N. seriolae were analyzed to investigate the potential role of gut microbiota. Results demonstrated that L. rhamnosus FS3051 and L. reuteri FS3052 inhibited N. seriolae, while B. subtilis natto NTU-18 did not inhibited N. seriolae. Probiotics also had the ability to secrete hydrolytic enzymes. Probiotic-fed grey mullet showed significant improvements in weight gain ratio, feed efficiency, and specific growth rate, particularly in the B. subtilis natto NTU-18 group. Immune gene expression was enhanced by probiotics, especially L. rhamnosus, FS3051, which induced IL-8, IL-1β, TNF-α, IFN-γ, and MHCI. Survival rates post-N. seriolae challenge improved significantly for L. rhamnosus FS3051-fed fish. L. rhamnosus FS3051 also altered the gut microbiota, enriching beneficial genera like Lactobacillus, which correlated positively with immune responses and growth, while reducing Mycoplasma and Rhodobacter, which were negatively correlated with immune responses. This study underscores the potential of probiotics in enhancing disease resistance and growth via regulating gut microbiota in grey mullet. [ABSTRACT FROM AUTHOR]

The gut microbiota (GM) and immune cells (IC) are increasingly recognized as key players in cancer development and progression. This study aimed to explore the potential mediating role of IC in the causal relationship between GM and thyroid cancer (TC) using Mendelian randomization (MR) analysis. Data from genome-wide association studies (GWAS) encompassing 473 GM species, 731 IC types, and TC were utilized. MR analysis identified nine GM species with significant causal relationships to TC, mediated by 10 IC phenotypes such as "Switched Memory AC," "IgD-CD38dim AC," and "EM DN (CD4-CD8-) AC." These findings suggest a complex interplay where specific IC mediate the effects of GM on TC risk. Sensitivity analyses confirmed the robustness of these results, with no evidence of horizontal pleiotropy. This study highlights potential mechanisms linking GM and IC to TC, offering insights that could inform GM-based immunotherapeutic strategies and IC-targeted interventions. However, further experimental research is needed to validate these causal pathways and better understand the underlying biological mechanisms. [ABSTRACT FROM AUTHOR]

Background: The Albumin-Bilirubin (ALBI) score and grade are widely used to stratify patients with primary biliary cholangitis (PBC) into different disease statuses and risk levels. Recent studies have increasingly highlighted the role of gut microbiota in autoimmune liver diseases. This study aimed to investigate the differences in gut microbiota among PBC patients with varying ALBI grades. Methods: Clinical data and stool samples were collected from outpatient and inpatient PBC patients between 2019 and 2022. Gut microbiota profiles were obtained using 16S rDNA sequencing of stool samples. We analyzed alpha diversity, beta diversity, LEfSe analysis and pathway function prediction. Additionally, various machine learning methods—including random forest (RF), lasso, gradient boosting machine (GBM) and support vector machine (SVM)—were employed to identify key features and to build and validate predictive models using bootstrap techniques. Results: Clinical characteristics of ALBI grade 1 patients were comparatively better than those of ALBI grade 2 and 3 patients, including multiple laboratory indices. Gut microbiota analysis revealed that species richness and balance were higher in ALBI grade 1 patients. Both the comparison of the most abundant genera and the linear discriminant analysis (LDA) in LEfSe demonstrated that Lachnospira had a higher abundance and better discriminative ability in ALBI grade 1. Pathway function prediction indicated that sulfur metabolism was upregulated in higher ALBI grades. Furthermore, RF identified 10 specific genera, which were then used to build and validate models for discriminating PBC patients according to their ALBI grades. All three models, developed using different machine learning methods, demonstrated good discrimination ability (mean AUC 0.75–0.80). Conclusion: This study highlights significant differences in gut microbiota profiles among PBC patients with different ALBI grades. The increased abundance of Lachnospira and upregulation of sulfur metabolism pathways are notable in patients with lower ALBI grades. The machine learning models developed based on gut microbiota features offer promising tools for discriminating between PBC patients with varying disease severities, which could enhance the precision of treatment strategies. [ABSTRACT FROM AUTHOR]

To explore the effects of hydroxyl‐α‐sanshool (HAS) administration on the intestinal health of high‐fat diet‐fed mice, mice were separated into a control (CN) group, a model (MC) group, a HAS (8 mg/kg bw) (HD) group, and a HAS (8 mg/kg bw) + Compound C (10 mg/kg·4 d) (HA) group. After 4 weeks of treatment, the mice were fasted for 12 h prior to sacrifice, and autopsy samples were taken for analysis. HAS improved inflammatory and metabolic imbalances by activating AMPK, as shown by biochemical, microbiota composition, and metabolomics analyses. These findings suggest that HAS can maintain intestinal health through AMPK‐mediated amino acid metabolism. [ABSTRACT FROM AUTHOR]

Primary biliary cholangitis (PBC) and gut microbiota (GM) are epidemiologically correlated but the causal inter-relationships remain poorly understood. We aim to explore the causal relationships between GM and PBC. Using the MiBioGen consortium, GWAS data for GM at the species level and the largest publicly available PBC GWAS data to date, we performed a bidirectional two-sample Mendelian randomization by the inverse variance weighted, MR-Egger, weighted median, weighted model and MR-PRESSO to elucidate the potential causal role of GM in PBC. To measure the heterogeneity of instrumental variables (IV), Cochran's Q statistic and MR-Egger intercept test were used. Genetically instrumented order Coriobacteriales (odds ratio [OR] = 2.18, 95% confidence interval [CI] 1.30–3.66, P = 0.004) significantly increased the risk for PBC, while genetically driven class Deltaproteobacteria (OR = 0.52, 95% CI 0.36–0.74, P = 0.002) causally decrease the NAFLD risk. Reverse MR analysis showed no significant association between PBC and the two specific GM. However, it indicated that PBC progression significantly increases the abundance of the class Bacteroidia, order Bacteroidales, and phylum Bacteroidetes (OR = 1.02, 95% CI 1.002–1.03, P = 0.026), while decreasing the abundance of the genus Lachnospiraceae UCG010 (OR = 0.98, 95% CI 0.96–0.995, P = 0.026). Our study demonstrated that genetically driven order Coriobacteriales and class Deltaproteobacteria were causally related to PBC risk. This causality provided a new perspective on ameliorating PBC by modulating GM. Our study demonstrated that genetically driven order Coriobacteriales and class Deltaproteobacteria were causally related to PBC risk. PBC was causally related to the abundance of four GM taxa(class Bacteroidia, order Bacteroidales, phylum Bacteroidetes and genus Lachnospiraceae UCG010). This causality provided a new perspective on ameliorating PBC by modulating GM. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is a highly prevalent pathogen in human gastric mucosa epithelial cells with strong colonization ability. Weizmannia coagulans is a kind of active microorganism that is beneficial to the improvement of host gut microbiota balance and can prevent and treat intestinal diseases. We investigated the beneficial effects of W. coagulans BC99 in H. pylori infected mice and measured inflammation response, oxidative stress, and gut microbiota. Results showed that BC99 could alleviate the gastric inflammation, inhibit the increasing of inflammation parameters endotoxin, interleukin‐10, transforming growth factor‐β, and interferon‐γ and oxidative stress myeloperoxidase and malondialdehyde, promote the levels of superoxide dismutase and catalase. Furthermore, 16S rRNA gene sequencing analysis revealed that BC99 reversed the change of gut microbiota by reducing the abundance of Olsenella, Candidatus_Saccharimonas, Monoglobus, and increasing the abundance of Tyzzerella. Meanwhile, BC99 caused elevated levels of Ligilactobacillus and Lactobacillus. In view of the beneficial effect of BC99 on the content of short‐chain fatty acid, valeric acid with sodium valerate interfered with H. pylori infection in mice found that valeric acid had a good restorative effect of H. pylori infection relating inflammation and oxidative stress responses. These results suggest that W. coagulans BC99 can be used as a potential probiotic to prevent and treat H. pylori infection by regulating the inflammation, oxidative stress, and gut microbiota. [ABSTRACT FROM AUTHOR]

Background Material and methods Results Conclusion The objective of the current study was to investigate the potential effects of syringin against dextran sulphate colitis (DSS)‐induced ulcerative colitis (UC) in mice.In vitro study was performed on the RAW 264.7 cells and cytokines and inflammatory level were estimated. The oxidative stress, inflammatory cytokines, apoptosis and inflammatory parameters were estimated. The mRNA expression and faecal samples were estimated in the colon tissue.Syringin treatment enhanced the body weight, colon length and reduced the disease activity index (DAI), spleen index. Syringin treatment remarkably suppressed the level of nitric oxide (NO), myeloperoxidase (MPO), intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule 1 (VCAM‐1) along with alteration of antioxidant parameters. Syringin treatment also altered level of cytokines in the serum and colon tissue; inflammatory parameters viz., platelet‐activating factor (PAF), cyclooxygenase‐2 (COX‐2), prostaglandin (PGE2), inducible nitric oxide synthetase (iNOS), nuclear factor κ‐B (NF‐κB); matrix metalloproteinases (MMP) level. Syringin significantly (p < 0.001) enhanced the level of nuclear factor erythroid 2‐related factor (Nrf2) and heme oxygenase‐1 (HO‐1). Syringin remarkably altered the relative abundance of gut microbiota like Firmicutes, Bacteroidetes, F/B ratio, Verrucomicrobia and Actinobacteria.Syringin exhibited the protective effect against DSS‐induced UC in mice via alteration of NF‐κB signalling pathway. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions This study aimed to evaluate the impact of antibiotic exposure on efficacy and adverse reactions in non‐small cell lung cancer (NSCLC) patients receiving chemoimmunotherapy, and to explore any specific associations on the basis of antibiotic class.A retrospective study was conducted on NSCLC patients who received chemoimmunotherapy in two Shandong hospitals between January 2018 and October 2023. The association between antibiotic exposure and progression‐free survival (PFS), overall survival (OS), objective response rate (ORR) and incidence of immune related adverse reactions (irAE) of patients were evaluated.Of the 316 patients, 134 (42.41%) received antibiotics (ATB group), and 182 (57.59%) did not (N‐ATB group). There was no significant difference in PFS (aHR = 1.009, 95% CI: 0.770–1.323; p = 0.946) or OS (aHR = 1.420, 95% CI: 0.986–2.047; p = 0.060) between ATB and N‐ATB groups. The impact on efficacy was related to the type of antibiotic. β‐Lactams (aHR = 1.737, 95% CI: 1.148–2.629; p = 0.009), in particular β‐lactam/β‐lactamase inhibitor combinations (BLBLIs) (aHR = 1.885, 95% CI: 1.207–2.944, p = 0.005) were associated with poorer OS. However, quinolones (aHR = 1.192, 95% CI: 0.861–1.650; p = 0.291) were not associated with OS. The incidence of irAEs was not significantly different between ATB and N‐ATB groups (p = 0.073), but was higher with BLBLIs (p = 0.013).In NSCLC patients receiving chemoimmunotherapy, no significant difference was observed in efficacy and incidence of irAEs between the ATB and the n‐ATB groups. In antibiotic class analysis, β‐lactams and specifically BLBLIs were observed to be associated with worse OS. [ABSTRACT FROM AUTHOR]

Lomatogonium rotatum (LR) is a folk medicinal herb traditionally used as a lipid-lowering and anti-obesity agent; but its pharmacological mechanism is unclear. In this study, we assessed the alterations of LR on gut microbes and serum metabolites in obese mice and their associated mechanisms of modulation on visceral fat and serum lipid by integrating gut microbiota and metabolomics analyses. Mice were fed a high-fat diet (HFD) to generate obesity and were then given LR and Orlistat orally at different doses (0.18, 0.9, 1.8 g/kg for LR and 0.048 g/kg for Orlistat) for a duration of 9 weeks. The impact of LR on weight loss was assessed through the examination of fat deposition, serum lipid indices, liver indices, and HE pathohistology. The effects of LR on gut microbiota and serum metabolites in obese mice were then investigated by 16S rRNA sequencing technology and untargeted metabolomics, and correlation analysis was performed. LR significantly reduced body weight, feed intake, Lee's index, visceral fat accumulation, serum TG, TC, AST and ALT, and elevated serum HDL levels in obese mice. In addition, 16S rRNA sequencing results indicated that the LR intervention remodeled microbial diversity and composition, increased the relative abundance of gut microbes Bacteroidetes and Porphyromonadaceae in HFD-induced obese mice, and decreased the Deferribacteres , Firmicutes and the Firmicutes/Bacteroidetes ratio. Correlation analyses showed that LR regulation of L-tyrosine and hesperetin metabolism, as well as alterations in the metabolic pathways of Phenylalanine, tyrosine and tryptophan biosynthesis, were associated with the changes in abundance of Bacteroidetes , Firmicutes, Porphyromonadaceae and Deferribacteres. Our study demonstrated that LR has lipid lowering and visceral fat reduction effects and its function may be closely related to the improvement of the gut microbiota and its associated metabolites. [ABSTRACT FROM AUTHOR]

In conservation strategies, getting precise and repeatable information on the species’ diet and health without relying on invasive or laborious methods is challenging. Here, we developed an efficient and non-invasive workflow for the sequencing and analysis of four taxonomic markers from fecal DNA to characterize the gut microbiota, parasites, and plants and lichens composing the winter diet of caribou (Rangifer tarandus), Canada’s most iconic endangered species. Sequencing of the 18S rRNA gene of eukaryotes from seven locations in Manitoba and Saskatchewan, Canada, allowed for the detection of five genera of parasites in caribou feces (including Nematodirella and Parelaphostrongylus) with variable frequency of occurrence depending on sampling location and sex. Our workflow also revealed a rich winter plant and lichen diet in caribou, with respectively 29 and 18 genera identified across all samples through plant and fungal ITS2 sequencing. Relationships between the gut microbiota and both the diet and parasite richness were also identified. Of note, the Central Saskatchewan sampling location was characterized by a clearly distinct gut microbiota which could be linked to an epiphytic lichen-rich diet. Overall, our results showed the potential of this multi-marker DNA metabarcoding workflow as an efficient tool to provide insights into the species biology and ecology. [ABSTRACT FROM AUTHOR]

Menopausal syndrome, occurring during the menopausal stage in women, manifests as symptoms stemming from decreased estrogen levels, such as hot flashes, insomnia, mental disorders (anxiety, depression), and osteoporosis. The bulk of studies have indicated alterations in the gut microbiota of those experiencing menopause syndrome compared to healthy women. However, This article focuses on the alterations in gut microbiota in perimenopausal women. Our study utilized 16 s rRNA sequencing to determine the differences in the gut microbiota and metabolites among 44 menopausal syndrome women. The distribution of gut microbiota in postmenopausal women varies based on the level of follicle stimulating hormone, with changes in gut microbiota abundance taking precedence over symptom onset. Fecal metabolites reveal changes in several metabolites, including Amino acid metabolism (Tyrosine, Tryptophan), Lipid metabolism (Alpha linolenic acid metabolism), and other metabolites. Disturbances in lipid metabolism, triggered by hormonal level fluctuations, can contribute to the development of osteoporosis. [ABSTRACT FROM AUTHOR]

Osteopontin (Opn) depletion can improve septic outcomes, but the underlying mechanism remains unknown. In this study, we demonstrated that nonhematopoietic but not hematopoietic Opn depletion improved septic outcomes. When compared with wild type mice, cohoused Opn −/− mice displayed enhanced production of antibacterial peptides (AMPs), decreased bacterial loads, and a distinct bacterial composition of gut microbiota. Fecal microbiota transplantation and OPN neutralization assay showed that Opn depletion could reduce bacterial loads and improve septic inflammation. By employing an intestinal organoid culture system, we proved that OPN neutralization in wild type organoids could inactivate AKT and decrease FOXO3a phosphorylation, resulting in enhanced AMP production, whereas OPN treatment in OPN-deficient organoids could activate AKT and increase FOXO3a phosphorylation, leading to reduced AMP production. Our findings identified OPN as a novel regulatory factor of AMP production to modulate bacterial loads and composition of gut microbiota, in turn affecting sepsis outcomes. [ABSTRACT FROM AUTHOR]

The gut microbiota influences multiple aspects of human health and disease. Several studies have indicated an association between the gut microbiota and response to immune checkpoint inhibitors in various cancers, but there is scarce data from breast cancer. The randomized ALICE trial demonstrated improved progression‐free survival (PFS) from adding the programmed cell death 1 ligand 1 (PD‐L1) inhibitor atezolizumab (atezo) to immunomodulating chemotherapy (chemo) in metastatic triple‐negative breast cancer (mTNBC), even for PD‐L1negative disease. Herein, we investigated the microbiota composition and dynamics in the ALICE patients and their association with clinical outcome, by analyzing fecal samples collected at baseline and after 8 weeks. We applied 16S (V3‐V4) rRNA sequencing to characterize the diversity and taxonomic composition. Kaplan–Meier and Cox proportional hazard models were used for time‐to‐event analyses. We found that high alpha diversity by Faith's phylogenetic diversity (PD) at baseline was associated with prolonged PFS in the total study population and in the atezo‐chemo arm, but not in the placebo‐chemo arm. Moreover, Faith's PD appeared to be predictive of benefit from atezolizumab. Patients with high Faith's PD exhibited a PFS hazard ratio of 0.34 (P = 0.018) in favor of the atezo‐chemo arm, compared to 0.83 (P = 0.62) in the low Faith's PD group. Faith's PD was significantly reduced during treatment. At baseline, Bifidobacterium was significantly overrepresented in patients without clinical benefit in the atezo‐chemo arm, but not in the placebo‐chemo arm. These findings suggest that alpha diversity by Faith's PD should be further investigated as a prognostic and predictive biomarker in patients with mTNBC receiving chemo‐immunotherapy. [ABSTRACT FROM AUTHOR]

Berries represent an important source of bioactive compounds, among which, (poly)phenols are the main constituents. (Poly)phenols have been shown to have important biological activities and in particular, to take a relevant role in mediating the modulation of gut microbiota and human health. Gut microbiota constitute significant players in the metabolism of ingested (poly)phenols and consequently in their biological effects. However, the evidence regarding the mutual contribution between (poly)phenol intake and gut microbiota activity in humans is still unclear. The aim of the current systematic review was to collect and assess results from randomized clinical trials addressing the role of berries in the modulation of the gut microbiota composition and how this can contribute to the metabolism of berry (poly)phenols. When information was available, the interaction of berry-gut microbiota on human health was evaluated. A total of 16 trials were included and analyzed. Overall, berries and their (poly)phenols could represent a driver for the modulation of intestinal microbes. The gut microbiota catabolize (poly)phenols by producing bioactive metabolites which can positively affect both the composition of commensal microbiota and also the host health. [ABSTRACT FROM AUTHOR]