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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.

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: 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]

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]

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]

Background: Gastrointestinal symptoms are now detected early in the clinical course of many dementia patients, and studies of the microbiome-gut-brain axis have confirmed bidirectional interactions between the gut and the brain. However, the causal relationship between gut microbiota and cognitive impairment has not been fully established. Therefore, this study conducted a bidirectional Mendelian randomization study to elucidate the potential causal relationship of gut microbiota to cognitive impairment. Objective: Using Mendelian randomization to identify gut flora with a genetic causal effect on the development of cognitive impairment. Methods: This study utilized publicly available genome-wide association study summary data to perform MR analysis, with gut microbiota as the exposure and various cognitive function indicators as well as scores for Alzheimer's disease as outcomes. This study selected single nucleotide polymorphisms as instrumental variables based on p-values, F-statistics, and r2. Bidirectional Mendelian randomization was conducted using methods such as inverse variance weighted, MR-Egger, simple mode, and weighted mode to assess the causal relationship. Concurrently, this study carried out Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis to identify potential heterogeneity and horizontal pleiotropy. Results: This study identified a total of 31 gut microbes that have a causal relationship with cognitive impairment, which include 1 phylum, 4 classes, 3 orders, 2 families, and 21 genera. Conclusions: This study unveiled specific gut microbiota associated with cognitive impairment, offering new insights and approaches for the prevention and treatment of cognitive impairment through gut microbiota such as Bifidobacterium and Ruminococcus gnavus group. [ABSTRACT FROM AUTHOR]

The human gut microbiota plays numerous roles in regulating host growth, the immune system, and metabolism. Age-related changes in the gut environment lead to chronic inflammation, metabolic dysfunction, and illness, which in turn affect aging and increase the risk of neurodegenerative disorders. Local immunity is also affected by changes in the gut environment. Polyamines are crucial for cell development, proliferation, and tissue regeneration. They regulate enzyme activity, bind to and stabilize DNA and RNA, have antioxidative properties, and are necessary for the control of translation. All living organisms contain the natural polyamine spermidine, which has anti-inflammatory and antioxidant properties. It can regulate protein expression, prolong life, and improve mitochondrial metabolic activity and respiration. Spermidine levels experience an age-related decrease, and the development of age-related diseases is correlated with decreased endogenous spermidine concentrations. As more than just a consequence, this review explores the connection between polyamine metabolism and aging and identifies advantageous bacteria for anti-aging and metabolites they produce. Further research is being conducted on probiotics and prebiotics that support the uptake and ingestion of spermidine from food extracts or stimulate the production of polyamines by gut microbiota. This provides a successful strategy to increase spermidine levels. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis explores alterations in the gut microbiota of patients with Multiple Sclerosis (MS) using 16S ribosomal RNA (rRNA) gene sequencing. Methods: Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, our comprehensive review spanned major databases, including PubMed, Web of Science, Embase, Cochrane, and Ovid, targeting observational studies that implemented 16S rRNA gene sequencing on fecal specimens. The quality of these studies was meticulously evaluated using the Newcastle-Ottawa scale. Results: Our search yielded 26 relevant studies conducted between 2015-2022, encompassing 2885 participants. No significant differences were observed in alpha diversity indices (Shannon, Chao1, Operational Taxonomic Units (OTU), and Simpson) between MS patients and controls in general. Nonetheless, subgroup analyses according to disease activity using the Shannon index highlighted a significant decrease in microbial diversity during MS's active phase. Similarly, an evaluation focusing on MS phenotype revealed diminished diversity in individuals with relapsing-remitting MS (RRMS). Microbial composition analysis revealed no consistent increase in pro-inflammatory Bacteroidetes or decrease in anti-inflammatory Firmicutes within the MS cohort. Conclusion: The gut microbiome's role in MS presents a complex panorama, where alterations in microbial composition might hold greater significance to disease mechanisms than diversity changes. The impact of clinical factors such as disease activity and phenotype are moderately significant, underscoring the need for further research to elucidate these relationships. Prospective research should employ longitudinal methodologies to elucidate the chronological interplay among gut microbiota, disease evolution, and therapeutic strategies. [ABSTRACT FROM AUTHOR]

BackgroundMethodsResultsConclusionEmerging evidence indicates that gut microbiota-targeted interventions may lead to improvements in cognition. We assessed whether a prebiotic-rich dietary intervention, probiotic supplement, or synbiotic combination of both would improve human cognition, as part of the ‘Gut Feelings’ trial.An 8-week, 2 × 2 factorial randomised controlled trial was conducted on 118 adults with low mood and potential for dietary improvement. Treatment arms: (1) probiotic supplement and diet-as-usual (probiotic group); (2) high-prebiotic diet and placebo supplement (prebiotic diet group); (3) probiotic supplement and high-prebiotic diet (synbiotic group); and (4) placebo supplement and diet-as-usual (placebo group). At baseline and 8-weeks, the Cogstate Brief Battery was administered, testing processing speed, attention, visual learning, and working memory. Data were analysed using Bayesian linear regression.We found weak evidence that the probiotic improved working memory (Cohen’s d = −0.32, 95% CI: –0.67, 0.03; posterior probability [post. prob] of benefit: 96%). For the other treatments, there was little or no evidence of cognitive improvement. We found weak evidence that the prebiotic diet impaired processing speed (d = 0.25, 95% CI: –0.02, 0.51; post. prob of harm: 97%). There was little indication of a synergistic interaction between the probiotic and prebiotic diet.We found suggestive evidence of a probiotic-induced improvement in working memory, and prebiotic-induced impairment in processing speed. However, the evidence remains inconclusive regarding any cognitive benefit or harm induced by the probiotic, prebiotic diet, or synbiotic treatments. Larger intervention studies are recommended, with inclusion of neuroimaging or electrophysiology measures.Trial Registration: Australian New Zealand Clinical Trials Registry (ACTRN12617000795392; registered 31 May 2017). [ABSTRACT FROM AUTHOR]

Background: Salmonella Typhimurium (S. Typhimurium) is a common pathogenic microorganism and poses a threat to the efficiency of poultry farms. As signaling molecules regulating the interaction between the host and gut microbiota, bile acids (BAs) play a protective role in maintaining gut homeostasis. However, the antibacterial effect of BAs on Salmonella infection in broilers has remained unexplored. Therefore, the aim of this study was to investigate the potential role of feeding BAs in protecting against S. Typhimurium infection in broilers. Methods: A total of 144 1-day-old Arbor Acres male broilers were randomly assigned to 4 groups, including non-challenged birds fed a basal diet (CON), S. Typhimurium-challenged birds (ST), S. Typhimurium-challenged birds treated with 0.15 g/kg antibiotic after infection (ST-ANT), and S. Typhimurium-challenged birds fed a basal diet supplemented with 350 mg/kg of BAs (ST-BA). Results: BAs supplementation ameliorated weight loss induced by S. Typhimurium infection and reduced the colonization of Salmonella in the liver and small intestine in broilers (P < 0.05). Compared to the ST group, broilers in ST-BA group had a higher ileal mucosal thickness and villus height, and BAs also ameliorated the increase of diamine oxidase (DAO) level in serum (P < 0.05). It was observed that the mucus layer thickness and the number of villous and cryptic goblet cells (GCs) were increased in the ST-BA group, consistent with the upregulation of MUC2 gene expression in the ileal mucosa (P < 0.05). Moreover, the mRNA expressions of Toll-like receptor 5 (TLR5), Toll-like receptor 4 (TLR4), and interleukin 1 beta (IL1b) were downregulated in the ileum by BAs treatment (P < 0.05). 16S rDNA sequencing analysis revealed that, compared to ST group, BAs ameliorated the decreases in Bacteroidota, Bacteroidaceae and Bacteroides abundances, which were negatively correlated with serum DAO activity, and the increases in Campylobacterota, Campylobacteraceae and Campylobacter abundances, which were negatively correlated with body weight but positively correlated with serum D-lactic acid (D-LA) levels (P < 0.05). Conclusions: Dietary BAs supplementation strengthens the intestinal mucosal barrier and reverses dysbiosis of gut microbiota, which eventually relieves the damage to the intestinal barrier and weight loss induced by S. Typhimurium infection in broilers. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) are key inducers of osteonecrosis, yet not all patients treated with GCs develop glucocorticoid-associated osteonecrosis (GAON). The factors mediating this relationship are unclear. Studies have shown that gut microbiota and their metabolites influence bone metabolism, but their role in GAON is unclear. This study aimed to explore the connection between GAON and gut microbiota. Through bidirectional Mendelian randomization analysis, we identified 14 gut microbial taxa, including Lachnospiraceae (IVW, P = 0.011), associated with GAON. RNA-seq analysis revealed that GAON differentially expressed genes (DEGs) were enriched for intestinal inflammatory response mechanisms. We then compared patients who developed GAON (17 cases), those who did not (GAnON, 15 cases), and those untreated with GCs (Blank, 15 cases) for gut microbiota composition, short-chain fatty acids (SCFAs), and serum inflammatory factors. Our findings indicated a decrease in Lachnospiraceae abundance (GAON 17.13%, GAnON 12.51%, Blank 24.52%) in GC-treated patients. Serum inflammatory factors (IL-17 A, IL-33, and TNF-α) associated with GAON (59.603 ± 12.147, 89.337 ± 20.714, 42.584 ± 9.185) showed significant differences between Blank (1.446 ± 0.683, 11.534 ± 4.705, 4.682 ± 1.48) and GAnON (25.353 ± 8.181, 32.527 ± 7.352, 12.49 ± 3.217) groups, with a negative correlation between these factors and Lachnospiraceae levels. Butyric acid levels in SCFAs varied among groups (P<0.01) and correlated with Lachnospiraceae and inflammatory factors. Controlled experiments in GAON rats demonstrated butyric acid's osteoprotective role in GAON development (P<0.01). In conclusion, our study suggests that reduced Lachnospiraceae and butyric acid levels, along with increased inflammation due to GCs use, contribute to GAON. Butyric acid may mediate the effects of Lachnospiraceae and inflammation. Butyrate supplementation could potentially reduce GAON incidence, offering a novel approach for its clinical management. [ABSTRACT FROM AUTHOR]

Background: Aflatoxin B1 (AFB1) is a mycotoxin that widely found in the environment and mouldy foods. AFB1 initially targets the intestine, and AFB1-induced intestinal injury cannot be ignored. Lactobacillus amylovorus (LA), a predominant species of Lactobacillus, plays a role in carbohydrate metabolism. Extracellular vesicles (EVs), small lipid membrane vesicles, are widely involved in diverse cellular processes. However, the mechanism by which Lactobacillus amylovorus-QC1H-derived EVs (LA.EVs) protect against AFB1-induced intestinal injury remains unclear. Results: In our study, a new strain named Lactobacillus amylovorus-QC1H (LA-QC1H) was isolated from pig faeces. Then, EVs derived from LA-QC1H were extracted via ultracentrifugation. Our results showed that LA.EVs significantly alleviated AFB1-induced intestinal injury by inhibiting the production of proinflammatory cytokines, decreasing intestinal permeability and increasing the expression of tight junction proteins. Moreover, 16 S rRNA analysis revealed that LA.EVs modulated AFB1-induced gut dysbiosis in mice. However, LA.EVs did not exert beneficial effects in antibiotic-treated mice. LA.EVs treatment increased intestinal levels of indole-3-acetic acid (IAA) and activated intestinal aryl hydrocarbon receptor (AHR)/interleukin-22 (IL-22) signalling in AFB1-exposed mice. Inhibition of intestinal AHR signalling markedly weakened the protective effect of LA.EVs in AFB1-exposed mice. Conclusions: LA.EVs alleviated AFB1-induced intestinal injury by modulating the gut microbiota, activating the intestinal AHR/IL-22 signalling, reducing the inflammatory response and promoting intestinal barrier repair in mice. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota may be involved in neuropathic pain. However, the causal association between gut microbiota and neuropathic pain remains unclear. Whether immune cells and inflammatory factors mediate the pathway from gut microbiota to neuropathic pain has not been elucidated. Methods: We obtained the summary data of 412 gut microbiota, 731 immune cells, 91 inflammatory factors, and five types of neuropathic pain (drug-induced neuropathy, postherpetic neuralgia, sciatica, trigeminal neuralgia, and unspecified neuralgia) from large-scale genome-wide association study (GWAS) datasets and the FinnGen database. We used bidirectional Mendelian randomization (MR) analysis to explore the causal association between gut microbiota and neuropathic pain. Additionally, we conducted a mediation analysis to identify whether immune cells and inflammatory factors act as mediators within these causal relationships. Results: Our study revealed 30 causal relationships between 26 gut bacterial taxa and five types of neuropathic pain, including four associated with drug-induced neuropathy, six with postherpetic neuralgia, five with sciatica, eight with trigeminal neuralgia, and seven with unspecified neuralgia. Moreover, we identified 35 gut bacterial pathway abundances causally involved in neuropathic pain. The reverse MR analysis showed no evidence of reverse causality from gut microbiota to neuropathic pain. Mediation analysis demonstrated that the immune cell phenotype "HLA-DR++ monocyte % leukocyte" mediated the causal relationship between p_Proteobacteria and sciatica with a mediation proportion of 36.15% (P = 0.038), whereas "CD11c on CD62L+ myeloid dendritic cell" mediated the causal pathway from assimilatory sulfate reduction to trigeminal neuralgia with a mediation proportion of 27.90% (P = 0.041). Conclusion: This study identified the causal relationships between several specific gut microbiota and various neuropathic pain subtypes. Additionally, two immune cells may act as potential mediators in the pathways from gut microbiota to neuropathic pain. [ABSTRACT FROM AUTHOR]

In consideration of the important influence of gut microbiota on colorectal cancer (CRC) development and host immune system, regulating microbiota and intestinal environment can be an assisting approach to CRC treatment. To remodel tumor microenvironment, the anti‐CRC molecular targeting drug regorafenib (REG)‐encapsulating nanoparticle (UIRN) is constructed with the amphiphilic inulin‐ursodeoxycholic acid conjugate. UIRN increases the intra‐tumoral concentration and accumulation time of REG. In the CT26 tumor‐bearing mouse model, the relative abundance of probiotics and short‐chain fatty acid concentrations in colon are upregulated after treatment with UIRN, with decreased proportion of pro‐tumoral bacteria. Combining gut microbiota modulation and the function of REG to induce polarization of tumor‐associated macrophages toward the M1‐type, UIRN conquers immunosuppression and enhances anti‐tumor immunity. UIRN not only efficiently controls tumor progression alone but also exhibits adjuvant effects to chemotherapy and immunotherapy agents. The microbiota‐regulating and tumor‐suppressing functions of UIRN also work in the colitis‐associated CRC model. With good biosafety, UIRN displays hopeful application prospects in CRC therapy. [ABSTRACT FROM AUTHOR]

Polyunsaturated fatty acids (PUFAs) are dietary components participating in neurotransmission and cell signaling. Pollen is a source of PUFAs for honeybees, and disruptions in dietary PUFAs reduce the cognitive performance of honeybees. We reveal that gut bacteria of honeybees contribute to fatty acid metabolism, impacting reward learning. Gut bacteria possess Δ-6 desaturases that mediate fatty acid elongation and compensate for the absence of honeybee factors required for fatty acid metabolism. Colonization with Gilliamella apicola , but not a mutant lacking the Δ-6 desaturase FADS2, increases the production of anandamide (AEA), a ligand of the endocannabinoid system, and alters learning and memory. AEA activates the Hymenoptera-specific transient receptor AmHsTRPA in astrocytes, which induces Ca2+ influx and regulates glutamate re-uptake of glial cells to enhance reward learning. These findings illuminate the roles of gut symbionts in host fatty acid metabolism and the impacts of endocannabinoid signaling on the reward system of social insects. [Display omitted] • Gut microbiota mediate the effects of PUFAs on honeybee reward learning and memory • Gilliamella apicola harboring FADS2 aids in converting LA to anandamide • Anandamide activates the AmHsTRPA channel in astrocytes, triggering Ca2+ influx • AmHsTRPA regulates the glutamate/GABA balance in astrocytes, promoting reward learning Zhong et al. reveal that honeybee gut microbiota influence reward learning by mediating the metabolism of pollen PUFAs. Gilliamella apicola harboring FADS2 facilitates the conversion of linoleic acid (LA) to anandamide, which activates AmHsTRPA in astrocytes. This activation triggers Ca2+ influx and regulates glutamate/GABA balance in glial cells, ultimately enhancing honeybee reward learning. [ABSTRACT FROM AUTHOR]

Animals' digestion, energy metabolism, and immunity are significantly influenced by interactions between the gut microbiota and the intestinal environment of the host. Previous studies have shown that gut microbiota of Eothenomys miletus can respond to environmental changes, high fiber or fat foods. But how E. miletus in high-altitude adapt to their environment through gut microbiota and physiological changes during winter food shortages period was unclear. In the present study, we evaluated the altitude differences in gut microbiota and their interactions with physiology in terms of body mass regulation in order to study the adaptation of the gut microbiota and physiological indicators of the E. miletus under food restriction settings. E. miletus were collected for this study from Jingdong County (JD, low-altitude) and Xianggelila County (XGLL, high-altitude) in Yunnan Province, China, and split into three groups: control group, food-restricted feeding group for 7 days, and re-feeding group was offered a standard diet for 14 days. 16S rRNA gene sequencing and physiological methods were used to analyze the abundance and community structure of gut microbiota, as well as physiological indicators of each group in E. miletus. The results showed that while the RMR changed more during the period of food restriction, the body mass and major organ masses of E. miletus from high-altitude changed less. After food restriction, RMR in XGLL decreased by 25.25%, while that of in JD decreased by 16.54%. E. miletus from the XGLL had gut bacteria that were more abundant in Firmicutes and had fewer OTUs, and the microbiota had a closer interaction with physiological indicators. Moreover, the gut microbiota adapted to the food shortage environment by enhancing the genera of Bacterroides , Ruminococcus , Turicibacter , and Treponema to improve the utilization of nutrient resources. The interactions between microbial species and the equilibrium of energy homeostasis were further impacted by alterations in physiological indicators and microbial community structure. These variations were important for E. miletus to adapt to the fluctuations and changes of food resources in high-altitude region, which also expand our knowledge of organismal adaptations and the mechanisms behind the interactions between gut bacteria and host physiology. [ABSTRACT FROM AUTHOR]

Endometriosis (EMT) has a significant impact on women's physical and mental health. In this study, high-throughput sequencing technology was employed to detect differences in gut microbiota between EMT patients and healthy individuals (CTL). Additionally, Spearman correlation analysis was utilized to analyze the correlation between different bacterial genera and EMT biomarkers (CA125 and CA199). The results demonstrated that at the phylum level, the relative abundances of Proteobacteria and Desulfobacterota_G_459546 in the EMT group were significantly higher than those in the CTL group, while the relative abundances of Bacteroidota and Firmicutes_A in the EMT group were significantly lower than those in the CTL group. At the genus level, the relative abundances of Burkholderiales and Sphingomonadales in the EMT group were significantly higher than those in the CTL group, while the relative abundances of Bacteroidales and Roseburia in the EMT group were significantly lower than those in the CTL group. The correlation analysis results show that CA125 and CA199 are significantly positively correlated with Burkholderiales and Sphingomonadales , and significantly negatively correlated with Bacteroidales , Oscillospirales , and Roseburia. The PICRUSt2 results show that the relative abundance in the cell motility and xenobiotics biodegradation and metabolism pathways in the EMT group was higher than that in the CTL group, while the relative abundance in the translation, replication and repair, folding, sorting and degradation, metabolism of terpenoids and polyketides and metabolism of cofactors and vitamins pathways in the EMT group was lower than that in the CTL group. In brief, there is a close correlation between the imbalance of gut microbiota and the onset of EMT. The intestinal microbiota has great significance broad prospects for the prevention, diagnosis and treatment of EMT. [ABSTRACT FROM AUTHOR]

Background: The symbiotic gut microbiota is pivotal for human health, with its composition linked to various diseases and metabolic disorders. Despite its significance, there remains a gap in systematically evaluating how host phenotypes, such as gender, age, and body mass index (BMI), influence gut microbiota. Methodology/principal findings: We conducted an analysis of the gut microbiota of 185 Chinese adults based on whole-metagenome shotgun sequencing of fecal samples. Our investigation focused on assessing the effects of gender, age, and BMI on gut microbiota across three levels: diversity, gene/phylogenetic composition, and functional composition. Our findings suggest that these phenotypes have a minor impact on shaping the gut microbiome compared to enterotypes, they do not correlate significantly within- or between-sample diversity. We identified a substantial number of phenotype-associated genes and metagenomic linkage groups (MLGs), indicating variations in gut microflora composition. Specifically, we observed a decline in beneficial Firmicutes microbes, such as Eubacterium , Roseburia , Faecalibacterium and Ruminococcus spp., in both older individuals and those with higher BMI, while potentially harmful microbes like Erysipelotrichaceae , Subdoligranulum and Streptococcus spp. increased with age. Additionally, Blautia and Dorea spp. were found to increase with BMI, aligning with prior research. Surprisingly, individuals who were older or overweight exhibited a lack of Bacteroidetes, a dominant phylum in the human gut microbiota that includes opportunistic pathogens, while certain species of the well-known probiotics Bifidobacterium were enriched in these groups, suggesting a complex interplay of these bacteria warranting further investigation. Regarding gender, several gender-associated MLGs from Bacteroides , Parabacteroides , Clostridium and Akkermansia were enriched in females. Functional analysis revealed a multitude of phenotype-associated KEGG orthologs (KOs). Conclusions/significance: Our study underscores the influence of gender, age, and BMI on gut metagenomes, affecting both phylogenetic and functional composition. However, further investigation is needed to elucidate the precise roles of these bacteria, including both pathogens and probiotics. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota (GM) has proven to be essential for both physical health and mental wellbeing, yet the forces that ultimately shape its composition remain opaque. One critical force known to affect the GM is the social environment. Prior work in humans and free-ranging non-human primates has shown that cohabitation and frequent social interaction can lead to changes in GM composition. However, it is difficult to assess the direction of causation in these studies, and interpretations are complicated by the influence of uncontrolled but correlated factors, such as shared diet. Results: We performed a 15-month longitudinal investigation wherein we disentangled the impacts of diet and social living conditions on GM composition in a captive cohort of 13 male cynomolgus macaques. The animals were in single housing for the first 3 months of the study initially with a variable diet. After baseline data collection they were placed on a controlled diet for the remainder of the study. Following this diet shift the animals were moved to paired housing for 6 months, enabling enhanced social interaction, and then subsequently returned to single housing at the end of our study. This structured sequencing of diet and housing changes allowed us to assess their distinct impacts on GM composition. We found that the early dietary adjustments led to GM changes in both alpha and beta diversity, whereas changes in social living conditions only altered beta diversity. With respect to the latter, we found that two particular bacterial families — Lactobacillaceae and Clostridiaceae — demonstrated significant shifts in abundance during the transition from single housing to paired housing, which was distinct from the shifts we observed based on a change in diet. Conversely, we found that other bacteria previously associated with sociality were not altered based on changes in social living conditions but rather only by changes in diet. Conclusions: Together, these findings decouple the influences that diet and social living have on GM composition and reconcile previous observations in the human and animal literatures. Moreover, the results indicate biological alterations of the gut that may, in part, mediate the relationship between sociality and wellbeing. [ABSTRACT FROM AUTHOR]

Background: The relationship between gut microbiota and osteoarthritis (OA) occurrence remains unclear. Existing research needs to clearly understand how basal metabolic rate (BMR) regulates this relationship. Therefore, using a two-step bidirectional Mendelian Randomization approach, our study aims to investigate whether BMR levels mediate the causal relationship between gut microbiota and OA. Methods: In this study, we examined publicly available summary statistics from Genome-Wide Association Studies (GWAS) to determine the correlation between gut microbiota and OA. The analysis included one primary dataset and two secondary datasets. Initially, a two-step, two-sample, and reverse MR analysis was performed to identify the causal relationship between gut microbiota and OA. Subsequently, a two-step MR analysis revealed that the relationship between microbiota and OA is mediated by BMR. Sensitivity analyses confirmed the robustness of the study results. Results: In our analysis of the primary dataset, we discovered a positive correlation between three taxa and the outcome of OA, and eight taxa exhibited a negative correlation with the OA outcome. Through comparisons with the secondary dataset and multiple testing corrections, we found a negative association between the class Actinobacteria (OR=0.992886277, p -value = 0.003) and the likelihood of OA occurrence. Notably, knee osteoarthritis (KOA) and hip osteoarthritis (HOA) had a strong negative correlation (OR = 0.927237553/0.892581219). Our analysis suggests that BMR significantly mediates the causal pathway from Actinobacteria to OA, with a mediated effect of 2.59%. Additionally, BMR mediates 3.98% of the impact in the path from the order Bifidobacteriales and the family Bifidobacteriaceae to OA. Besides these findings, our reverse analysis did not indicate any significant effect of OA on gut microbiota or BMR. Conclusion: Our research results indicate that an increase in the abundance of specific gut microbial taxa is associated with a reduced incidence of OA, and BMR levels mediate this causal relationship. Further large-scale randomized controlled trials are necessary to validate the causal impact of gut microbiota on the risk of OA. This study provides new insights into the potential prevention of OA by modulating the gut microbiota. [ABSTRACT FROM AUTHOR]

Background: Primary immune thrombocytopenia (ITP) is an immune-mediated hematologic disorder characterized by a reduction in platelet count, increasing the risk of bleeding. Recent studies have indicated a close association between alterations in gut microbiota and the development of ITP. However, the mechanisms by which gut microbiota influence the occurrence and progression of ITP through plasma metabolites remain poorly understood. Evidence suggests extensive interactions between gut microbiota and plasma metabolites, implying a potential role for gut microbiota in influencing ITP through alterations in plasma metabolites, which requires further investigation. Methods: In this study, summarized GWAS data (including 211 gut microbiota taxa, 1,400 plasma metabolites or ratios, and an ITP patient cohort) were retrieved from the MiBioGen and GWAS Catalog databases. Using a two-sample Mendelian randomization (MR) approach, we screened gut microbiota and plasma metabolites potentially causally related to ITP. We further identified plasma metabolites serving as mediators through which gut microbiota affect ITP and calculated the strength of the mediation effect. To ensure result stability, we primarily used the inverse variance weighted (IVW) method as the main judgment index. We also utilized MR Egger and inverse variance weighted methods to detect heterogeneity in the results, and employed MR-Egger and MR-PRESSO methods to assess the presence of pleiotropy. Results: Though two-sample MR analysis, 8 gut microbiota taxa were found to have causal relationships with ITP. After excluding six plasma metabolites with pleiotropy, 39 plasma metabolites were found to be causally related to ITP (P < 0.05). Eleven plasma metabolites were identified as having causal relationships between gut microbiota and plasma metabolites. Finally, using the delta method, it was calculated that Sphingomyelin levels (8.0%, 95%CI: 0.9% to 11.5%, P = 0.047) and Glucose-to-mannose ratio (6.5%, 95%CI: 0.7% to 9.5%, P = 0.039) are intermediates for Intestinimonas influencing ITP, while Bilirubin (Z,Z) to etiocholanolone glucuronide ratio (5.6%, 95%CI: 4.7% to 6.9%, P = 0.043) is an intermediate for Senegalimassilia influencing ITP. Conclusion: Gut microbiota can influence the development of ITP through changes in plasma metabolites. Sphingomyelin levels, Glucose-to-mannose ratio, and Bilirubin (Z,Z) to etiocholanolone glucuronide ratio are newly discovered intermediates through which gut microbiota influence ITP, providing potential indicators and targets for clinical diagnosis and treatment. This study highlights the intricate relationship between gut microbiota and plasma metabolites in the context of ITP, suggesting new avenues for clinical diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Glucose oxidase (GOD) has been investigated as a potential additive for enhancing intestinal health and growth performance in poultry. However, limited research exists on the effects of ultra-high doses of GOD in practical poultry production. This study aimed to investigate the impact of high dietary GOD levels on broiler growth performance, antioxidant capacity, and intestinal microbiota. A total of 400 healthy, 1-day-old, slow-growing broiler chickens were randomly assigned to four treatment groups. The control group was fed a standard basal diet, while the other groups (G1, G2, and G3) were fed the basal diet supplemented with 4 U/g, 20 U/g, and 100 U/g of VTR GOD, respectively. The results showed that a dose of 100 U/g GOD significantly improved the final body weight and average daily feed intake (ADFI) (p < 0.05). Additionally, the G3 group exhibited a marked increase in glutathione peroxidase (GSH-Px) activity (p < 0.05), reflecting enhanced antioxidant function. Gut morphology remained intact across all groups, indicating no adverse effects on intestinal barrier integrity. Microbiota analysis revealed significant increases (p < 0.05) in Firmicutes and Verrucomicrobiota abundance at the phylum level in the GOD-supplemented groups. Moreover, GOD treatments significantly increased the abundance of Faecalibacterium , Mucispirllum , and CHKCI001 at the genus level. Metabolic function predictions suggested that high-dose GOD supplementation enriched carbohydrate metabolism, particularly starch and sucrose metabolism. Correlation analysis indicated that Faecalibacterium and CHCKI001 were two bacteria strongly influenced by GOD supplementation and were associated with enhanced growth performance and improved gut health. In conclusion, high-dose GOD supplementation had no adverse effects and demonstrated significant benefits, promoting both growth performance and gut health in broilers. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide, with obesity-induced lipid metabolism disorders playing a crucial role in its progression. A complex connection exists between gut microbiota and the development of intestinal tumors through the microbiota metabolite pathway. Metabolic disorders frequently alter the gut microbiome, impairing immune and cellular functions and hastening cancer progression. Methods: This study thoroughly examined the gut microbiota through 16S rRNA sequencing of fecal samples from 181 CRC patients, integrating preoperative Low-density lipoprotein cholesterol (LDL-C) levels and RNA sequencing data. The study includes a comparison of microbial diversity, differential microbiological analysis, exploration of the associations between microbiota, tumor microenvironment immune cells, and immune genes, enrichment analysis of potential biological functions of microbe-related host genes, and the prediction of LDL-C status through microorganisms. Results: The analysis revealed that differences in α and β diversity indices of intestinal microbiota in CRC patients were not statistically significant across different LDL-C metabolic states. Patients exhibited varying LDL-C metabolic conditions, leading to a bifurcation of their gut microbiota into two distinct clusters. Patients with LDL-C metabolic irregularities had higher concentrations of twelve gut microbiota, which were linked to various immune cells and immune-related genes, influencing tumor immunity. Under normal LDL-C metabolic conditions, the protective microorganism Anaerostipes_caccae was significantly negatively correlated with the GO Biological Process pathway involved in the negative regulation of the unfolded protein response in the endoplasmic reticulum. Both XGBoost and MLP models, developed using differential gut microbiota, could forecast LDL-C levels in CRC patients biologically. Conclusions: The intestinal microbiota in CRC patients influences the LDL-C metabolic status. With elevated LDL-C levels, gut microbiota can regulate the function of immune cells and gene expression within the tumor microenvironment, affecting cancer-related pathways and promoting CRC progression. LDL-C and its associated gut microbiota could provide non-invasive markers for clinical evaluation and treatment of CRC patients. [ABSTRACT FROM AUTHOR]

Previous studies have suggested a potential association between the gut microbiota and arthritis. However, the causal links between the gut microbiota and various types of arthritis, as well as the potential mediating role of inflammatory proteins, remain unclear. Mendelian randomization was used to explore the causal relationships between gut microbiota, inflammatory proteins, and various forms of arthritis (osteoarthritis, rheumatoid and psoriatic arthritis, and ankylosing spondylitis [AS]). The inverse variance-weighted method was the primary analytical approach used. Furthermore, we examined the mediating role of inflammatory proteins in the pathway linking the gut microbiota to arthritis. Sensitivity analyses were performed to verify the robustness of the findings, and enrichment analyses were conducted to investigate the biological functions and pathways involved. We identified 11 positive and 14 negative causal effects linking the genetic liability of the gut microbiota to arthritis. Similarly, 9 positive and 8 negative causal effects between inflammatory proteins and arthritis were identified. Notably, an increased abundance of the order Bacillales (odds ratio [OR] = 1.199, 95% confidence interval [CI] = 1.030–1.394, P = 0.019) and higher interleukin-7 levels (OR = 1.322, 95% CI = 1.004–1.741, P = 0.046) significantly elevated the risk of AS. Furthermore, interleukin-7 mediated 13.8% of the effect caused by the order Bacillales, with a mediation effect size of β = 0.025 (95% CI = 0.001–0.064). Sensitivity and supplementary analyses revealed no significant evidence of horizontal pleiotropy or heterogeneity. Overall, our findings demonstrate causal links between the gut microbiota, inflammatory proteins, and four arthritis types, highlighting the gut microbiota as a potential therapeutic target. Crucially, interleukin-7 not only strongly correlated with AS but also partially mediated the effect exerted by the gut microbiota on AS, suggesting that managing the gut microbiota to modulate inflammatory proteins could serve as an effective therapeutic strategy for arthritis. [ABSTRACT FROM AUTHOR]

Staphylococcal Enterotoxin C2 (SEC2), a classical superantigen, is an antitumor immunotherapy agent. However, the injectable formulation of SEC2 limits its clinical application. Here, it is reported that oral administration of SEC2 activates the intestinal immune system and benefits intestinal health in a mouse model. These results indicate that intact SEC2 is detected in the stomach, intestine, and serum after oral administration. Continuous oral administration of SEC2 activates immune cells in gut‐associated lymphoid tissues, promoting extensive differentiation and proliferation of CD4+ and CD8+ T cells and CD19+ B cells, leading to increased production of cytokines and secretory immunoglobulin A. SEC2 also enhances intestinal barrier function, as demonstrated by an increased villus length/crypt depth ratio and elevated expression of mucins and tight junction proteins. Additionally, SEC2 indirectly influenced gut microbiota, reinforcing potential probiotics and short‐chain fatty acid synthesis. Enhanced differentiation of T and B cells in the spleen, coupled with elevated serum interleukin‐2 levels, suggests systemic immune enhancement following oral administration of SEC2. These findings provide a scientific basis for the development of SEC2 as an oral immunostimulant for immune enhancement and anti‐tumor immunotherapy. [ABSTRACT FROM AUTHOR]