Maintenance hemodialysis (MHD) patients frequently exhibit immune dysregulation and gut dysbiosis, both of which contribute to increased infection risk and adverse outcomes. However, the relationship between gut microbial composition and immune competence in this population remains underexplored.

This study assessed 45 MHD patients and 30 healthy controls, stratifying MHD patients into immunocompetent (HD-NLI, CD4+/CD8+ ≥ 1) and immunodeficient (HD-LI, CD4+/CD8+ < 1) groups. Circulating cytokines (IL-6, IL-10, IL-12, TNF-α, IFN-γ) were quantified using ELISA. Gut microbiota profiles were derived via 16S rRNA gene sequencing (V3-V4 regions), followed by QIIME2 and LEfSe-based bioinformatics analyses.

HD-LI patients displayed severe T cell dysregulation and elevated pro-inflammatory cytokines. Compared to controls, HD patients had reduced abundance of beneficial taxa (e.g., Prevotella copri, Bacteroides vulgatus, Agathobacter), and enrichment of pro-inflammatory taxa (e.g., Escherichia-Shigella, Blautia, Citrobacter). LEfSe identified 39 discriminatory taxa with distinct immune group signatures. Redundancy analysis revealed that CD4+ levels, CD4+/CD8+ ratios, and TNF-α significantly shaped microbiota composition. Correlation analysis confirmed strong associations between immune parameters and microbial taxa involved in short-chain fatty acid (SCFA) metabolism.

This study provides novel evidence linking gut microbial dysbiosis to immune impairment in MHD patients. The findings suggest that SCFA-producing bacteria are depleted in immunodeficient states, offering a potential target for microbiota-directed immunomodulatory therapies in ESRD.

Polycystic ovary syndrome (PCOS) is a metabolic disorder disease strongly associated with gut microbiota (GM). Zishen Qingre Lishi Huayu recipe (ZQLHR), a traditional Chinese medicinal compound, has patented and shown therapeutic effects in treating PCOS in clinical trials without clear pharmacological mechanisms. This study aimed to disclose the potential therapeutic mechanism of ZQLHR on PCOS.

We firstly confirmed the therapeutic effects of ZQLHR treatment in PCOS patients. 16 S rRNA sequencing, untargeted metabolomics, fecal microbiota transplantation (FMT), high performance liquid chromatography (HPLC) and Person's correlation analysis were conducted to elucidate the potential therapeutic mechanism.

These results showed that PCOS symptoms in ZQLHR patients were significantly ameliorated. ZQLHR could increase the levels of butyrate-producing Lachnospira and Faecalibacterium and decrease the abundance of Escherichia-Shigella. Untargeted metabolomics showed that ZQLHR significantly improved host metabolic function, particularly butyrate metabolism and citrate cycle (TCA cycle) metabolism. The combined Faecalibacterium and butyrate metabolism datasets were correlated. Stool samples from ZQLHR patients could ameliorate ovarian architecture, significantly reduce testosterone (T), estradiol (E2) and luteinizing hormone (LH) levels and increased follicle-stimulating hormone (FSH) levels and increase the content of butyric acid in PCOS mice (P < 0.01). Moreover, the correlation analysis showed that some biochemical parameters (T, E2, LH levels and FSH) and butyric acid were correlated.

We firstly depicted that ZQLHR could alleviate the series of symptom in women with PCOS by regulating gut microbiota and butyrate metabolism. This study provides a scientific basis and new ideas for the therapy of PCOS.

Intestinal microbiota possess a plethora of biotransformation capabilities, which can modify medications, including their Phase I or II metabolites in a process termed "Phase IV" metabolism. Phase IV metabolism is emerging as a significant contributor to interindividual variability in drug responses. Here we present examples of gastrointestinal-relevant medications that are known to be subject to bacterial Phase IV metabolism and propose avenues to improve precision medicine by modulating these bacterial functions.

The gut microbiota has emerged as a critical determinant of immune checkpoint inhibitor (ICI) efficacy, resistance, and toxicity. Retrospective and prospective studies profiling the taxonomic composition of intestinal microbes of patients treated with ICI have revealed specific gut microbial signatures associated with response. By contrast, dysbiosis, which can be caused by chronic inflammatory processes (such as cancer) or comedications, is a risk factor of resistance to ICI. Recent large-scale meta-analyses have confirmed that antibiotic (ATB) use before or during ICI therapy alters the microbiota repertoire and significantly shortens overall survival, even after adjusting for prognostic factors. These results underscore the importance of implementing ATB stewardship recommendations in routine oncology practice. Microbiota-centered interventions are now being explored to treat gut dysbiosis and optimize ICI responses. Early-phase clinical trials evaluating fecal microbiota transplantation (FMT) from ICI responders or healthy donors have shown that this approach is safe and provided preliminary data on potential efficacy to overcome both primary and secondary resistance to ICI in melanoma, non-small cell lung cancer, and renal cell carcinoma. More targeted interventions including live bacterial products including Clostridium butyricum and Akkermansia massiliensis represent novel microbiome-based adjunct therapies. Likewise, dietary interventions, such as high-fiber diets, have shown promise in enhancing ICI activity. In this ASCO Educational Book, we summarize the current state-of-the-evidence of the clinical relevance of the intestinal microbiota in cancer immunotherapy and provide a practical guide for ATB stewardship.

Diabetes mellitus is a significant public health issue. Despite the emergence of promising anti-hyperglycemic drugs, treatment outcomes for diabetic patients continue to be inadequate. Gypenosides are the major bioactive compounds isolated from Gynostemma pentaphyllum (Thunb.) Makino. Gynostemma pentaphyllum has longstanding history of usage in traditional oriental medicine, particularly for the treatment of diabetes mellitus. Gypenosides were found to exhibit antidiabetic effects. This review outlined the advancements in the preclinical studies of gypenosides' pharmacological properties on diabetes mellitus and their potential mechanism of action, while also noting the lack of clinical evidence for gypenosides' efficacy.

Literatures search was done using scientific databases PubMed, Web of Science, Scopus and Google Scholar up to November 2024 utilizing keywords such as "Gynostemma pentaphyllum", "gypenoside*", and "diabet*".

Research has shown that gypenosides possess therapeutic properties in mitigating diabetes mellitus by regulating blood glucose levels and insulin production. Gypenosides can modulate various key pathways associated with diabetes pathogenesis, including PI3K/Akt, PPARγ, NF-κB, AMPK and PDX1, hence contributing to their antidiabetic properties. Nevertheless, there is a paucity of research on gypenosides in clinical settings, with existing studies being mainly conducted on animal models and in vitro. Future studies with the focus on the isolation and purification of specific gypenosides, as well as the exploration on the probable pharmacological effect and molecular mechanisms behind the biological actions are necessary.

The findings presented may establish a foundation for subsequent clinical trials for the development of specific gypenosides as antidiabetic therapies for the betterment of human health.

As part of the IBD Character initiative, we examined an inception cohort and investigated mucosal microbiota composition and transcriptional activity in relation to clinical outcomes.

A cohort of 237 individuals were included from five countries: Crohn's disease (CD, n = 72), ulcerative colitis (UC, n = 57), symptomatic non-IBD controls (SC, n = 78) and healthy controls (HC, n = 30). Rectal/colonic biopsies were obtained at inclusion, and DNA and RNA were extracted from the same biopsy and examined by sequencing the 16S rRNA V4 region.

Beta diversity measurements separated IBD from both HC and SC. IBD and SC exhibited reduced intra-individual diversity compared with HC. When comparing taxonomy at DNA and RNA level, six bacteria were found to differ in abundance and/or transcriptional activity between IBD and symptomatic control, while there were 14 and three between symptomatic control and CD and UC, respectively. A limited number of bacterial taxa were responsible for the largest difference between presence and activity, separating patients and controls. Multiple bacterial taxa were associated with treatment escalation in both UC and CD. Machine-learning models separated IBD from symptomatic controls and treatment escalators from non-escalators (AUC >0.8). However, the differential effects were mainly driven by clinical biomarkers, such as f-calprotectin, s-albumin, and b-hemoglobin.

Differences between presence and transcriptional activity were found among multiple taxa when assessing 16S rRNA at DNA and RNA level. Symptomatic controls were more similar to the IBD patients compared to HC. The analyses suggest that the mucosal microbiota carries a moderate diagnostic and predictive potential, outcompeted by f-calprotectin.

Chemical signatures encode the physicochemical and structural properties of small molecules into numerical descriptors, forming the basis for chemical comparisons and search algorithms. The increasing availability of bioactivity data has improved compound representations to include biological effects (for example, induced gene expression changes), although bioactivity descriptors are often limited to a few well-documented molecules. To address this issue, we implemented a collection of deep neural networks able to leverage the experimentally determined bioactivity data associated to small molecules and infer the missing bioactivity signatures for any compound of interest. However, unlike static chemical descriptors, these bioactivity signatures dynamically evolve with new data and processing strategies. Here we present a computational protocol to modify or generate novel bioactivity spaces and signatures, describing the main steps needed to leverage diverse bioactivity data with the current knowledge, as catalogued in the Chemical Checker (CC; https://chemicalchecker.org/ ), using the predefined data curation pipeline. We illustrate the functioning of the protocol through four specific examples, including the incorporation of new compounds to an already existing bioactivity space, a change in the data preprocessing without altering the underlying experimental data and the creation of two novel bioactivity spaces from scratch, which are completed in under 9 h using graphics processing unit computing. Overall, this protocol offers a guideline for installing, testing and running the CC data integration approach on user-provided data, extending the annotation presented for a limited number of small molecules to a larger chemical landscape and generating novel bioactivity signatures.

The use of tacrolimus (TAC), a critical immunosuppressant post transplantation, is complicated by its high pharmacokinetic variability. While the gut microbiota has gained attention as a potential contributor, few studies have assessed its role in TAC metabolism variability. This study investigated the associations between the gut microbiota and TAC metabolism rates in kidney transplant recipients during the first month post transplantation-a crucial period for adjusting TAC to achieve therapeutic levels. We recruited 20 kidney transplant recipients and profiled their gut microbiota diversity and composition from stool samples collected before transplantation and at weeks 1 and 4 post transplantation via 16S rRNA sequencing. The TAC pharmacokinetic parameters were also collected. Associations between TAC metabolism status or pharmacokinetic parameters and gut microbiota diversity and composition were evaluated. Recipients with a fast TAC metabolism rate (C0/D ratio < 1.05 ng/mL × 1/mg) presented significantly greater changes in both bacterial alpha and beta diversity metrics at 1 week post transplantation than did those with a slow metabolism rate (C0/D ratio ≥ 1.05 ng/mL × 1/mg). Compared with slow metabolizers, fast metabolizers were associated with a significant increase in the abundance of three bacterial genera (Faecalibacterium, Clostridia vadinBB60, and Ruminococcus) and a significant decrease in the abundance of two bacterial species (Bacteroides plebeius and Parabacteroides goldsteinii). This study revealed links between gut microbiota diversity and composition and TAC metabolism rates in kidney transplant recipients during the early posttransplant period, underscoring the importance of investigating the gut microbiota as a contributor to TAC pharmacokinetic variability. Clarifying this causal relationship could better predict inter- and intraindividual TAC pharmacokinetic variability.

Understanding the risk and protective factors associated with Parkinson's disease (PD) is crucial for improving outcomes for patients, individuals at risk, healthcare providers, and healthcare systems. Studying these factors not only enhances our knowledge of the disease but also aids in developing effective prevention, management, and treatment strategies. This paper reviews the key risk and protective factors associated with PD, with a particular focus on the biological mechanisms underlying these factors. Risk factors include genetic mutations, racial predispositions, and environmental exposures, all of which contribute to an increased likelihood of developing PD or accelerating its progression. Conversely, protective factors, such as regular physical exercise, adherence to a Mediterranean diet, and higher urate levels, have the potential to reduce inflammation and support mitochondrial function, thereby mitigating the risk of disease. However, identifying and validating these factors presents significant challenges. These challenges include the absence of reliable biomarkers, intricate interactions between genetic and environmental components, and clinical heterogeneity observed in patients with PD. These barriers complicate the establishment of clear causal relationships and hinder the development of targeted preventive strategies. To overcome these challenges, we propose several solutions and recommendations. Understanding the mechanisms underlying risk factors may inform future research aimed at developing standardized and more accurate biomarkers for PD, facilitating earlier diagnosis and improved monitoring of disease progression. Additionally, we offer actionable recommendations for PD prevention and management tailored to healthy individuals, patients diagnosed with PD, and healthcare systems. These strategies aim to improve clinical outcomes, enhance the quality of life, and optimize healthcare delivery for PD.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disorder characterized by persistent fatigue and cognitive impairments, with emerging evidence highlighting the role of gut health in its pathophysiology. The main objective of this review was to synthesize qualitative and quantitative data from research examining the gut microbiota composition, inflammatory markers, and therapeutic outcomes of interventions targeting the microbiome in the context of ME/CFS.

The data collection involved a detailed search of peer-reviewed English literature from January 1995 to January 2025, focusing on studies related to the microbiome and ME/CFS. This comprehensive search utilized databases such as PubMed, Scopus, and Web of Science, with keywords including "ME/CFS," "Gut-Brain Axis," "Gut Health," "Intestinal Dysbiosis," "Microbiome Dysbiosis," "Pathophysiology," and "Therapeutic Approaches." Where possible, insights from clinical trials and observational studies were included to enrich the findings. A narrative synthesis method was also employed to effectively organize and present these findings.

The study found notable changes in the gut microbiota diversity and composition in ME/CFS patients, contributing to systemic inflammation and worsening cognitive and physical impairments. As a result, various microbiome interventions like probiotics, prebiotics, specific diets, supplements, fecal microbiota transplantation, pharmacological interventions, improved sleep, and moderate exercise training are potential therapeutic strategies that merit further exploration.

Interventions focusing on the gut-brain axis may help reduce neuropsychiatric symptoms in ME/CFS by utilizing the benefits of the microbiome. Therefore, identifying beneficial microbiome elements and incorporating their assessments into clinical practice can enhance patient care through personalized treatments. Due to the complexity of ME/CFS, which involves genetic, environmental, and microbial factors, a multidisciplinary approach is also necessary. Since current research lacks comprehensive insights into how gut health might aid ME/CFS treatment, standardized diagnostics and longitudinal studies could foster innovative therapies, potentially improving quality of life and symptom management for those affected.

The gut microbiota represents a rich and adaptive microbial network inhabiting the gastrointestinal tract, performing key functions in nutrient processing, immune response modulation, intestinal wall protection, and microbial defense. Its composition remains highly personalized and responsive to external influences, including lifestyle patterns, physical activity, body composition, and nutritional intake. The interactions of the gut microbiota with bodily systems are conventionally interpreted as broad systemic impacts on organ balance. Yet, emerging research-exemplified by the gut microbiota-brain axis-suggests the potential existence of more targeted and direct communication mechanisms. Dysbiosis, characterized by microbial ecosystem disturbance, generates multiple metabolic compounds capable of entering systemic circulation and reaching distant tissues, notably including ocular structures. This microbial imbalance has been associated with both systemic and localized conditions linked to eye disorders. Accumulating scientific evidence now supports the concept of a gut-retina axis, underscoring the significant role of microbiota disruption in generating various retinal pathologies. This review comprehensively investigates gut microbiota composition, functional dynamics, and dysbiosis-induced alterations, with specific focus on retinal interactions in age-related macular degeneration, diabetic retinopathy, glaucoma, and retinal artery occlusion. Moreover, the review explores microbiota-targeted therapeutic strategies, including precision nutritional interventions and microbial transplantation, as potential modulators of retinal disease progression.

Fecal calprotectin (FC) is a biomarker of gut inflammation but its association with sepsis associated liver dysfunction (SALD) is unclear. This single-center, prospective cohort study investigated the relationship between FC and SALD in adults with sepsis. FC concentrations were measured on days 1 (FC1) and 3 (FC3). The difference between FC3 and FC1 (∆FC) was calculated. The relationship between FC and SALD was assessed using multivariate analysis. Receiver operating characteristic curves were used to assess the predictive value of SALD biomarkers. Ninety-five patients with sepsis (33 with SALD and 62 without SALD) were enrolled between January 2023 and March 2024. The median FC3 level and ∆FC were significantly higher in the SALD group than in the non-SALD group (both p < 0.001), whereas the median FC1 level did not differ significantly between groups. FC3 level and ∆FC were positively associated with SALD in the adjusted analysis (both p < 0.001) with areas under the curve of 0.784 and 0.848, respectively, and cut-off values of 930.88 μg/g and - 8.80 μg/g, respectively. In adults with sepsis, SALD occurrence was more strongly associated with elevated FC3 levels and ∆FC than with FC1 levels; therefore, monitoring FC3 levels and ∆FC could help detect SALD.

Recently, the gut microbiota has been found to be associated with multiple organs and systems in the human body, playing a key role in the occurrence and development of various diseases, such as the gut-brain axis and the gut-liver axis. However, its interaction with miscarriages remains poorly understood. This article reviews the characteristics of gut microbiota and its metabolites in patients with recurrent spontaneous abortion (RSA), the mechanism of gut microbiota inducing RSA, and potential therapeutic strategies. Therefore, it provides a new perspective on the gut microbiota in the pathogenesis and treatment of recurrent abortion, and the prospect of the future research direction of gut microbiota and recurrent abortion is proposed based on existing studies.

Although natural polysaccharides often have growth-promoting effects on animals, little is known about how polysaccharides act when they are administered as feed additives. This work shows that Amomum longiligulare polysaccharide 1 (ALP1) improves the growth performance of piglets by promoting the proliferation of jejunal epithelial cells. ALP1 improves the growth performance of piglets, increasing the average daily gain by 32.71 % and reducing the feed-to-gain (F/G) ratio by 21.93 %. The gut microbiota is an important regulatory target of polysaccharides. The results of jejunal microbiota transplantation trials indicate that the jejunal microbiota from ALP1-fed piglets exhibits better growth performance and that the F/G ratio is reduced by 12.72 %. Furthermore, 16S rDNA sequencing and nontargeted metabolomic analyses reveal that ALP1 supplementation can increase the abundance of Lactobacillus in the jejuna of piglets, resulting in a high abundance of 11Z-eicosenoic acid (EA). In addition, EA increases the villus height-to-crypt depth (VH/CD) ratio in the jejunum by 27.41 %, potentially increasing epithelial cell proliferation. These results suggest that oral ALP1 supplementation promotes growth by modulating the composition of the jejunal microbiota and its associated metabolites.

The human body is habitat to a wide spectrum of microbial populations known as microbiota, which play an important role in overall health. The considerable research has mostly focused on the gut microbiota due to its potential to impact numerous physiological functions and its correlation with a variety of disorders, such as cardiovascular diseases (CVDs). Imbalances in the gut microbiota, known as dysbiosis, have been linked to the development and progression of CVDs through various processes, including the generation of metabolites like trimethylamine-N-oxide and short-chain fatty acids. Studies have also looked at the idea of using therapeutic interventions, like changing your diet, taking probiotics or prebiotics, or even fecal microbiota transplantation (FMT), to change the gut microbiota's make-up and how it works in order to prevent or treat CVDs. Exploring the cause-and-effect connection between the gut microbiota and CVDs offers a hopeful path for creating innovative microbiome-centered strategies to prevent and cure CVDs. This review presents an in-depth review of the correlation between the gut microbiota and CVDs, as well as potential therapeutic approaches for manipulating the gut microbiota to enhance cardiovascular health.

The importance of the intestinal microbita in a multitude of physiological processes is well-evidenced. These include metabolism of nutrients and xenobiotics, biosynthesis of vitamin K and vitamin B12, immunomodulation, maintenance of the gut mucosal barrier integrity and protection against some pathogens. Interindividual differences in the intestinal microbiota composition have impacts on health. The bioavailability and activity of some pharmaceuticals are heavily influenced by interindividual variability in metabolism, which has a genetic basis. This variability, primarily occurring in the liver but also in the intestine, has been studied extensively. Despite the advancement of this field - pharmacogenetics - its integration into clinical practice remains limited for reasons discussed herein. This highlights the even greater challenge of applying emerging knowledge on variability in the gut microbiota to drug therapy. However, ignoring these opportunities would be a mistake. While clinical applications of microbiota-guided drug therapy are currently absent and the ideas in this article are largely theoretical, research is uncovering that in cases where a substantial portion of a drug or its metabolites reaches the colon, or where drugs are formulated for colonic delivery, the gut microbiota can significantly affect drug metabolism and activity. Greater focus should be placed on research into how interindividual variability in the intestinal microbiome can modify pharmaceutical bioavailability and activity. This article is deliberately speculative and exploratory but proposes that, though there are still no clinical examples of microbiome-guided drug therapy, these interactions could afford opportunities for improvements in personalised medicine and also for drug design.

Everyday actions such as eating, tooth brushing or applying cosmetics inherently modulate our microbiome. Advances in sequencing technologies now facilitate detailed microbial profiling, driving intentional microbiome-targeted product development. Inspired by an academic-industry workshop held in January 2024, this review explores the oral, skin and gut microbiomes, focussing on the potential long-term implications of perturbations. Key challenges in microbiome safety assessment include confounding factors (ecological variability, host influences and external conditions like geography and diet) and biases from experimental measurements and bioinformatics analyses. The taxonomic composition of the microbiome has been associated with both health and disease, and perturbations like regular disruption of the dental biofilm are essential for preventing caries and inflammatory gum disease. However, further research is required to understand the potential long-term impacts of microbiome disturbances, particularly in vulnerable populations including infants. We propose that emerging technologies, such as omics technologies to characterize microbiome functions rather than taxa, leveraging artificial intelligence to interpret clinical study data and in vitro models to characterize and measure host-microbiome interaction endpoints, could all enhance the risk assessments. The workshop emphasized the importance of detailed documentation, transparency and openness in computational models to reduce uncertainties. Harmonisation of methods could help bridge regulatory gaps and streamline safety assessments but should remain flexible enough to allow innovation and technological advancements. Continued scientific collaboration and public engagement are critical for long-term microbiome monitoring, which is essential to advancing safety assessments of microbiome perturbations.

Epimedin C, an anti-cardiovascular disease natural compound derived from Herba Epimedii, exhibits low oral bioavailability, with its metabolism closely related to the gut microbiota. In this study, we investigated the roles of intestinal bacteria in the catabolism of epimedin C. We discovered that a strain of Parabacteroides distasonis QZH 1201 (P. distasonis) from human fecal samples can convert epimedin C to 2"-O-rhamnosylicariside II and baohuoside I. More importantly, we identified an α-L-rhamnosidase enzyme from P. distasonis (PdRha), which plays a crucial role in this process by efficiently transforming epimedin C into icariside I. PdRha showed optimal activity at pH 6 and a temperature of 50 °C. Under the condition that the final concentration of epimedin C was 0.5 mM, its conversion efficiency reached 78.72 %. Additionally, we investigated the substrate profile of PdRha and discovered that it can hydrolyze rutin, naringin, and icariin, releasing isoquercitrin, prunin, and icariside I. Molecular docking was performed to gain insights into the enzymatic mechanism. This study provides valuable insights into how a common intestinal symbiotic bacterium processes an important natural flavonoid.

Immunosuppression often leads to drastic metabolic, hormonal, and physiological disorders. Changes in the gut microbiota are believed to be one of the factors contributing to these disorders, but the association remains uncertain. Clinical studies can be complicated by confounding variables, such as diet and other drivers of heterogeneity in human microbiomes. In this study, we identified pronounced gut microbiome signatures in rhesus macaques (RMs) with immunosuppression-induced lipid metabolism disorders following cyclosporine combined with dexamethasone. Furthermore, we observed similar changes in the gut microbiota of mice with immunosuppression-induced lipid metabolism disorders, which were associated with short-chain fatty acid metabolism. ELISA showed that immunosuppression significantly reduced the levels of butyric acid in both feces and serum of mice. Spearman correlation analysis identified a significant correlation between serum butyric acid levels and gut microbial dysbiosis induced by immunosuppression, particularly in relation to f_Lachnospiraceae, g_unidentified_Ruminococcaceae, and s_Clostridium leptum. Additionally, mice transplanted with gut microbiota from immunosuppressed mice exhibited hepatic lipid metabolism disorders, and RNA sequencing revealed significant downregulation of ABC transporters and PPARα in the liver, which was closely associated with lipid transport and metabolism, particularly Abca1. Moreover, butyric acid supplementation alleviated hepatic lipid metabolism disorders and upregulated the expression of Abca1 and PPARα in mice transplanted with immunosuppression-induced gut microbiota. Thus, we propose that the combination of cyclosporine and dexamethasone regulates the expression of hepatic Abca1 and PPARα by modulating the gut microbiota and its derived butyrate, particularly Lachnospiraceae and Clostridium leptum, further regulating hepatic lipid metabolism.

Diabetic periodontitis presents a unique therapeutic challenge, primarily due to its chronic inflammatory profile and the associated bone loss driven by immune dysregulation. Metformin (Met) is recognized for its potent anti-inflammatory properties, yet its limited cellular uptake has hindered its clinical effectiveness in diabetic periodontitis. A tetrahedral framework nucleic acid (tFNA)-based delivery system is developed to enhance Met cellular uptake and investigate its effects on diabetic periodontitis in this study. The tFNA-loaded Met complex (TMC) demonstrates efficient Met loading efficiency and rapid cellular internalization. These results show that in vitro, TMC significantly inhibited pro-inflammatory cytokines and matrix metalloproteinaseat both mRNA and protein levels under high glucose conditions. Mechanistically, TMC suppresses NLRP3-mediated pyroptosis by downregulating NLRP3, Caspase-1, Caspase-11, and GSDMD, ultimately reducing Mature-IL-1β and Mature-IL-18 production. Furthermore, TMC activates AMPK while inhibiting NF-κB signaling, thus mitigating the inflammatory response in diabetic periodontitis. In vivo, intraperitoneal administration of TMC in a diabetic periodontitis mouse model significantly reduces inflammatory cell infiltration, collagen degradation, and osteoclast formation, thus alleviating alveolar bone loss. These findings highlight the therapeutic potential of tFNA as an efficient Met delivery vehicle to tackle diabetic periodontitis-associated inflammation and bone resorption, providing a promising strategy for managing diabetic complications.

Metabolic abnormalities and gut microbiota imbalance are intricately linked to the onset and progression of Alzheimer's disease (AD). Kai-Xin-San (KXS) is a traditional herbal formula known for its therapeutic effects on AD. Our previous research indicated that Kai-Xin-San polysaccharide (KXS-P) exhibits a significant therapeutic impact on AD, but the precise mechanisms remain incompletely understood. In this study, untargeted fecal metabolomics and 16S rRNA gene sequencing were used to investigate the potential mechanisms by which KXS-P acts against AD. Key metabolites and gut microbial species were identified using multivariate analysis and a comprehensive examination of intestinal microecology. Our findings revealed that KXS-P improves lipid metabolism in AD rats by modulating a series of lipid molecules and bile acid levels. Additionally, KXS-P regulated gut microbiota composition and restored the symbiotic relationships within the gut microbiome. Notably, the anti-inflammatory effect of KXS-P may be related to its regulation of specific lipotypes levels and the abundance of Romboutsia, Bifidobacterium and Alloprevotella. KXS-P demonstrates the ability to alleviate symptoms of AD rats through multiple mechanisms: ① Improving lipid metabolism and maintaining lipid homeostasis; ② Reducing neuronal and inflammatory damage; ③ Regulating the composition and symbiotic relationships of gut microbiota to preserve intestinal microecological balance.

Several previous observational studies have shown that abnormal sphingomyelin metabolism may be implicated in the pathogenesis of Alzheimer's disease. To determine the causal relationship between sphingolipid abundance and gut microbiota abundance at the genetic level, we conducted a Mendelian randomization (MR) investigation.

We first used the TwoSampleMR and MRPRESSO packages for conducting two-sample MR studies. Second, we utilized random effect inverse variance weighting (IVW) as the principal method of analysis and used MR‒Egger, the weighted median, the simple mode and the weighted mode as supplementary methods. Finally, we performed tests for heterogeneity and horizontal pleiotropy. These analyses were also conducted to evaluate the impact of individual SNPs on the outcomes of our analysis. A Bonferroni-corrected threshold of p = 2.4e-4(0.05/211) was considered significant, and p values less than 0·05 were considered to be suggestive of an association.

The results showed that sphingolipid levels were suggestively associated with the abundance of 6 gut microbiota taxa. Specifically, two taxa were positively correlated with sphingolipid levels, including the family Alcaligenaceae (p = 0.006, OR 95% CI = 1.109 [1.030-1.194]) and the species Ruminococcus callidus (p = 0.034, OR 95% CI = 1.217 [1.015-1.460]). In contrast, negative correlations were observed with the abundances of 4 gut microbiota taxa, including the genus Flavonifractor (p = 0.026, OR 95% CI = 0.804 [0.663-0.974]), the genus Streptococcus (p = 0.014, OR 95% CI = 0.909 [0.842-0.981]), the species Bacteroides caccae (p = 0.037, OR 95% CI = 0.870 [0.763-0.992]), and the species Haemophilus parainfluenzae (p = 0.006, beta 95% CI = -0.269 [-0.462, -0.076]). The results presented a normal distribution, with no anomalous values, heterogeneity, or horizontal pleiotropic effects detected.

This two-sample MR study revealed a potential causal relationship between sphingomyelin levels and gut microbiota abundance.

Disruptions in the gut microbiota metabolism may contribute to the pathophysiology of gut-brain interaction disorders, and correction of intestinal dysbiosis is considered a promising therapeutic approach. Menthacarin, a proprietary fixed combination of Mentha x piperita L. and Carum carvi L. essential oils, is used clinically for the treatment of functional dyspepsia and irritable bowel syndrome. Rodent model data indicate that treatment effects of Menthacarin on visceral hypersensitivity could be mediated via the normalization of gut dysbiosis. However, the impact of Menthacarin on human bacterial gut microbiota has not yet been studied.

The aim of the present study was to assess whether Menthacarin affects the composition and metabolic activity of human fecal microbiota.

Fecal slurry samples from 10 healthy volunteers were cultivated for 36 h under anoxic conditions with and without Menthacarin. Relative bacterial abundance at the phylum and genus levels was evaluated using 16S rRNA metagenomic analysis. Short-chain fatty acids (SCFAs) in the supernatants were measured using the LC-MS technology.

Menthacarin induced robust changes in microbial composition at both the phylum and genus levels among the 10 donor microbiomes. The relative abundance of Firmicutes (+13.6 ± 8.6%) and Actinobacteria (+54.9 ± 47.6%) significantly increased, whereas that of Bacteroidetes (-27.7% ± 21.9%) and Proteobacteria (-25.7% ± 12.3%) significantly decreased in the presence of Menthacarin. At the genus level, the most notable changes were significant increases in Bifidobacterium (+105.1 ± 78.4%) and several SCFA-producing genera accompanied by a significant decrease in genera containing members involved in pro-inflammatory processes. In addition, Menthacarin significantly increased the levels of several SCFAs, namely, propionate, butyrate, isobutyrate, valerate, and isovalerate.

Menthacarin alters the microbiota composition and enhances SCFA production in human microbiota samples under in vitro conditions. These effects may contribute to the clinical benefits observed with Menthacarin treatment.

Introduction: Many orally administered drugs are either unstable in the acidic environment of the stomach or cause moderate to severe side effects in the upper gastrointestinal tract (GIT). These limitations can reduce therapeutic efficacy, discourage patient compliance, worsen the disease, and even contribute to the risk of cancer development. To overcome these issues, drug release often needs to be modified and targeted to the distal parts of the GIT. This is typically achieved through the use of pH-sensitive polymer coatings or incorporation into polymeric delivery systems. With this in mind, the aim of this project was to design, develop, and characterize gellan gum-based beads for colon-specific prolonged release of mesalazine, with potential application in the chemoprevention and treatment of bowel diseases. Materials and Methods: The dehydrated capsules were characterized using Raman spectroscopy and scanning electron microscopy. The crosslinked gellan gum was additionally evaluated for cytotoxicity. Key parameters such as pH-dependent swelling behavior, drug content, encapsulation efficiency, and drug release in simulated gastrointestinal fluids were also assessed. Furthermore, the behavior of the capsules in the gastrointestinal tract was studied in a rat model to evaluate their in vivo performance. Results: Significant differences in drug release profiles were observed between formulations crosslinked solely with calcium ions and those additionally crosslinked with glutaraldehyde (GA). The incorporation of GA effectively prolonged the release of mesalazine. These findings were further supported by in vivo studies conducted on Wistar rats, where the GA-crosslinked formulation demonstrated a markedly extended release compared to the formulation prepared using only ionotropic gelation. Conclusions: The combination of ionotropic gelation and glutaraldehyde crosslinking in gellan gum-based beads appears to be a promising strategy for achieving colon-specific prolonged release of mesalazine, facilitating targeted delivery to the distal regions of the gastrointestinal tract.

Similarity between candidate drug targets and human proteins is commonly assessed to minimize the occurrence of side effects. Although numerous drugs have been found to disrupt the health of the human microbiome, no comprehensive comparison between established drug targets and the human microbiome metaproteome has yet been conducted. Therefore, herein, sequence and structure alignments between human and pathogen drug targets and representative human gut, oral, and vaginal microbiome metaproteomes were performed. Both human and pathogen drug targets were found to be similar in sequence, function, structure, and drug binding capacity to proteins in diverse pathogenic and non-pathogenic bacteria from all three microbiomes. The gut metaproteome was identified as particularly susceptible overall to off-target effects. Certain symptoms, such as infections and immune disorders, may be more common among drugs that non-selectively target host microbiota. These findings suggest that similarities between human microbiome metaproteomes and drug target candidates should be routinely checked.

Over 10 million children in the world have epilepsy, with an unknown cause in half of the cases. The gut microbiome has been associated with various neurological disorders, and certain drugs greatly disturb the microbiome. Our aim was to study the association of prenatal and childhood exposure (before the age of two) to antibiotics, proton pump inhibitors (PPIs) and histamine-2 receptor antagonists, and the risk of childhood epilepsy. Using population-based registers, we included all live singleton births in Sweden from 2006 to 2017. Exposure was considered prescription(s) to antibiotics, proton pump inhibitors, or H2-receptor antagonists (separately). Multivariable Cox regression was used to calculate hazard ratios and 95% confidence intervals. 708,903 mother-child dyads were included, and 0.5% of children had an epilepsy diagnosis. Average follow-up was 3.8 years (IQR 1-6). Prenatal exposure to antibiotics (aHR 1.09, 95% CI 1.01-1.18) and PPIs (aHR 1.38, 95% CI 1.17-1.65) were associated with an increased risk of epilepsy. Exposure to antibiotics (1.11, 95% CI 1.02-1.21), PPIs (3.40, 95% CI 2.47-4.68) and H2RAs (1.65, 95% CI 1.03-2.64) before the age of two was associated with an increased risk of epilepsy after the age of two. Dose response analysis showed that one prescription of antibiotics in pregnancy or early life was not associated with an increased risk of epilepsy, while one prescription of PPIs in pregnancy or early life had an association. To conclude, our results support the hypothesis that microbiome modulating drugs are associated with an increased risk of epilepsy. This needs to be further validated in other studies, ideally including indications for drug use.

Fusobacterium nucleatum (F. nucleatum) is an anaerobic bacterium known for its association with periodontal disease and oral infections. It has been implicated in the development of gastrointestinal diseases such as inflammatory bowel disease and colorectal cancer. Ulcerative colitis (UC), which is characterized by chronic inflammation of the colon, is a condition of unknown etiology with a rising incidence rate, significantly affecting the quality of life for patients. The increased intestinal permeability during UC may facilitate the adherence or invasion of F. nucleatum into the damaged intestinal barrier, leading to exacerbated inflammation.

This article introduces the concept of the oral-gut axis, reviewing existing literature to analyze the role of F. nucleatum in the pathogenesis of UC and exploring its potential pathogenic mechanisms. It also summarizes the latest advances in treating patients with UC who have F. nucleatum and looks forward to prospective therapeutic strategies and the translational prospects of F. nucleatum within the oral-gut axis.

F. nucleatum may be a key player in the pathogenesis of UC, likely due to its invasiveness during periods of increased intestinal permeability. The paper also discusses innovative approaches for the prevention and management of UC exacerbated by F. nucleatum, paving the way for more effective treatment of UC.

The review offers new insights into the complex relationship between the oral microbiome and intestinal diseases, enhancing our understanding of their dynamic interactions. There is a paucity of literature on therapeutic approaches, indicating a need for further clinical research.

Microbiota-mediated drug metabolism can affect pharmacological efficacy. Here we conducted a systematic comparative metabolomics investigation of drug metabolism modes by evaluating the impacts of human gut commensal bacteria on 127 G-protein-coupled receptor (GPCR)-targeted drugs. For the most extensively metabolized drugs in our screen, we elucidated both conventional and unconventional drug transformations and the corresponding activities of generated metabolites. Comparisons of drug metabolism by a gut microbial community versus individual species revealed both taxon intrinsic and collaborative processes that influenced the activity of the metabolized drugs against target GPCRs. We also observed iloperidone inactivation by generating unconventional metabolites. The human gut commensal bacteria mixture incorporated sulfur in the form of a thiophene motif, whereas Morganella morganii used a cascade reaction to incorporate amino-acid-derived tricyclic systems into the drug metabolites. Our results reveal a broad impact of human gut commensal bacteria on GPCR-targeted drug structures and activities through diverse microbiota-mediated biotransformations.

Bifidobacteria represent a dominant constituent of human gut microbiomes during infancy, influencing nutrition, immune development, and resistance to infection. Despite interest in bifidobacteria as a live biotic therapy, our understanding of colonization, host-microbe interactions, and the health-promoting effects of bifidobacteria is limited. To address these major knowledge gaps, we used a large-scale genetic approach to create a mutant fitness compendium in Bifidobacterium breve. First, we generated a high-density randomly barcoded transposon insertion pool and used it to determine fitness requirements during colonization of germ-free mice and chickens with multiple diets and in response to hundreds of in vitro perturbations. Second, to enable mechanistic investigation, we constructed an ordered collection of insertion strains covering 1,462 genes. We leveraged these tools to reveal community- and diet-specific requirements for colonization and to connect the production of immunomodulatory molecules to growth benefits. These resources will catalyze future investigations of this important beneficial microbe.

Biological factors affect the human microbiome, highlighting the need for reasonably estimating sample sizes in future population studies.

We assessed the temporal stability of fecal microbiome diversity, species composition, and genes and functional pathways through shallow shotgun metagenome sequencing. Using intraclass correlation coefficients (ICC), we measured biological variability over 6 months. We estimated case numbers for 1:1 or 1:3 matched case-control studies, considering significance levels of 0.05 and 0.001 with 80% power, based on the collected fecal specimens per participant.

The fecal microbiome's temporal stability over 6 months varied (ICC < 0.6) for most alpha and beta diversity metrics. Heterogeneity was seen in species, genes, and pathways stability (ICC, 0.0-0.9). Detecting an OR of 1.5 per SD required 1,000 to 5,000 cases (0.05 significance for alpha and beta; 0.001 for species, genes, and pathways) with equal cases and controls. Low-prevalence species needed 15,102 cases, and high-prevalence species required 3,527. Similar needs applied to genes and pathways. In a 1:3 matched case-control study with one fecal specimen, 10,068 cases were needed for low-prevalence species and 2,351 for high-prevalence species. For ORs of 1.5 with multiple specimens, cases needed for low-prevalence species were 15,102 (one specimen), 8,267 (two specimens), and 5,989 (three specimens).

Detecting disease associations requires a large number of cases. Repeating prediagnostic samples and matching cases to more controls could decrease the needed number of cases for such detections.

Our results will help future epidemiologic study designs and implement well-powered microbiome studies.

The human gastrointestinal tract harbors a vast array of microorganisms, which play essential roles in maintaining metabolic balance and immune function. While bacteria dominate the gut microbiome, fungi represent a much smaller, often overlooked fraction. Despite their relatively low abundance, fungi may significantly influence both health and disease. Advances in next-generation sequencing, metagenomics, metatranscriptomics, metaproteomics, metabolomics, and computational biology have provided novel opportunities to study the gut mycobiome, shedding light on its composition, functional genes, and metabolite interactions. Emerging evidence links fungal dysbiosis to various diseases, including inflammatory bowel disease, colorectal cancer, metabolic disorders, and neurological conditions. The gut mycobiome also presents a promising avenue for precision medicine, particularly in biomarker discovery, disease diagnostics, and targeted therapeutics. Nonetheless, significant challenges remain in effectively integrating gut mycobiome knowledge into clinical practice. This review examines gut fungal microbiota, highlighting analytical methods, associations with human diseases, and its potential role in precision medicine. It also discusses pathways for clinical translation, particularly in diagnosis and treatment, while addressing key barriers to implementation.

The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.

Neurodevelopmental disorders (NDDs) encompass a range of disruptive conditions with varying prevalence rates and multiple contributing factors. Recent studies have suggested a potential connection between NDDs and the gut-brain axis. Furthermore, there is evidence indicating that nutritional supplements might have an impact on gastrointestinal (GI) and behavioral symptoms. This study aimed to explore the effects of nutritional supplements on the gut microbiota and behavioral symptoms in individuals with NDDs.

A systematic search of databases such as PubMed, Scopus, Web of Science, Embase, and APA PsycINFO was conducted, utilizing relevant keywords until February 2025. In addition, the search for gray literature was carried out on Google Scholar and ProQuest. The risk of bias was assessed using the ROBINS-I tool for non-randomized studies and the RoB-1 tool for randomized controlled trials. Due to the heterogeneity of the studies, a Synthesis without Meta-analysis (SWiM) approach was employed.

The overall findings from the studies indicated positive effects of supplementation in reducing the Gastrointestinal Severity Index (GIS) score and alleviating GI symptoms. Supplementation with probiotics and vitamins increased good microbiomes (GM) and decrease in bad microbiomes (BM) among individuals with autism spectrum disorder (ASD). Moreover, the Firmicutes to Bacteroidetes ratio (F/R ratio) exhibited significant changes after supplementation. Additionally, improvements were observed in various assessment scores, including ATEC, ABC, CARS, and PGI-2.

Nutritional supplementation in individuals with NDDs can have a positive influence by modulating the microbiome, reducing dysbiosis, and enhancing gut barrier integrity. Shifting in the F/R ratio can be considered as the reason for improving gastrointestinal and behavioral symptoms by influencing neurotransmitter activity and neuroinflammation. Targeting the gut-brain axis with interventions that focus on gut microbiota offers a promising adjunct therapy for the management of NDD. Registration of the review protocol. PROSPERO registration no. CRD42023460449.

Background: Hepatobiliary liver cancers (HBLCs) represent the sixth most common neoplasm in the world. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) constitute the main HBLC types, with alarming epidemiological projections. Methods: In recent decades, alterations in gut microbiota, with mutual implications on the gut-liver axis and gut-biliary axis permeability status, have been massively investigated and proposed as HBLC pathogenetic deus ex machina. Results: In the HCC setting, elevated intestinal levels of Escherichia coli and other Gram-negative bacteria have been demonstrated, resulting in a close association with increased lipopolysaccharide (LPS) serum levels and, consequently, chronic systemic inflammation. In contrast, the intestinal microbiota of HCC individuals feature reduced levels of Lactobacillus spp., Bifidobacterium spp., and Enterococcus spp. In the CC setting, evidence has revealed an increased expression of Lactobacillus spp., with enhanced levels of Actynomices spp. and Alloscardovia spp. Besides impaired strains/species representation, gut-derived metabolites, including bile acids (BAs), short-chain fatty acids (SCFAs), and oxidative-stress-derived products, configure a network severely impacting the progression of HBLC. Conclusions: In the era of Precision Medicine, the clarification of microbiota composition and functioning in HCC and CC settings can contribute to the identification of individual signatures, potentially providing novel diagnostic markers, therapeutic approaches, and prognostic/predictive tools.

The use of nonfood prebiotics, probiotics, and synbiotics has approximately tripled in the last 20 years. It is necessary to examine the associations of these substances with all-cause and cause-specific mortality in a large prospective cohort.

This study included 53,333 adults from the National Health and Nutrition Examination Survey 1999-2018. All participants answered questions on the use of dietary supplements and medications, including prebiotics, probiotics, and synbiotics. Death outcomes were determined by linkage to National Death Index records through 31 December 2019. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality from all causes, heart diseases, cancer, and other causes.

During a mean follow-up of 10.6 years, 9117 deaths were documented, including 2364 heart disease deaths, 1964 cancer deaths, and 4700 other causes deaths. Compared to nonusers, nonfood prebiotic, probiotic, and synbiotic users had a 59% (HR 0.41, 95% CI 0.30 to 0.56), 56% (HR 0.44, 95% CI 0.26 to 0.74), 49% (HR 0.51, 95% CI 0.31 to 0.83), and 64% (HR 0.36, 95% CI 0.23 to 0.59) for lower risk of all-cause, cancer, heart disease, and other causes mortality, respectively. Moreover, the inverse association of the use of prebiotics, probiotics, and synbiotics with mortality was stronger in female participants and participants without hypertension.

The use of nonfood prebiotics, probiotics, and synbiotics is significantly associated with lower all-cause mortality, as well as deaths from heart disease, cancer, and other causes.

The gut microbiome functions as a metabolic organ, producing numerous enzymes that influence host health; however, their substrates and metabolites remain largely unknown.

We present MicrobeRX, an enzyme-based metabolite prediction tool that employs 5487 human reactions and 4030 unique microbial reactions from 6286 genome-scale models, as well as 3650 drug metabolic reactions from the DrugBank database (v.5.1.12). MicrobeRX includes additional analysis modules for metabolite visualization and enzymatic and taxonomic analyses. When we applied MicrobeRX to 1083 orally administered drugs that have been approved in at least one jurisdiction at some point in time (DrugBank), it predicted metabolites with physicochemical properties and structures similar to metabolites found in biosamples (from MiMeDB). It also outperformed another existing metabolite prediction tool (BioTransformer 3.0) in terms of predictive potential, molecular diversity, reduction of redundant predictions, and enzyme annotation.

Our analysis revealed both unique and overlapping metabolic capabilities in human and microbial metabolism and chemo- and taxa-specific microbial biotransformations. MicrobeRX bridges the genomic and chemical spaces of the gut microbiome, making it a valuable tool for unlocking the chemical potential of the gut microbiome in human health, the food and pharmaceutical industries, and environmental safety. Video Abstract.

This study aimed to evaluate the therapeutic effect of Terminalia chebula (TC) on Tibetan yak-origin Salmonella-induced diarrhea and dysentery in mice. The levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α), anti-inflammatory cytokines (IL-4 and IL-10), and the oxidative stress markers malondialdehyde (MDA), superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), reduced glutathione (GSH-PX), and catalase (CAT) in the serum of mice were measured using ELISA kits. Using microbial diversity sequencing and non-targeted metabolomics detection techniques, the relevant mechanisms of TC treatment in a mouse Salmonella infection model were evaluated. The results showed the following: TC can effectively reduce the diarrhea rate; alleviate weight loss caused by Salmonella invasion; reduce the pro-inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α in serum; and increase the concentrations of the anti-inflammatory cytokines IL-4 and IL-10. TC can improve the body's antioxidant levels to heal the damage caused by oxidative stress and lipid peroxidation. The histological section results show that TC can significantly improve gastric and intestinal tissue lesions and has no toxic effects on the liver and kidneys. 16S rRNA and ITS sequencing analysis suggests that Lactobacillus, Enterorhabdus, Alistipes (bacterial community), Lodderomyces, Saccharomyces, and Penicillium (fungal community) may be key functional microbial communities in TC. Non-targeted metabolomics also suggests that the antibacterial treatment of dysentery with chebulic acid may be related to regulation of the Ras signaling pathway, long-term potentiation, the MAPK signaling pathway, metabolic pathways, and gut microbiome composition. Conclusion: TC has clear clinical efficacy in treating bacterial diarrhea, presenting anti-inflammatory and antioxidant effects. Its roles in regulating the gut microbiome and metabolic pathways and products were determined as the main reason for its therapeutic effect in a mouse gastroenteritis model caused by Salmonella infection.