Search Results (495)

Background/Objectives: Children and young people (CYP) with a learning disability are at higher risk of living with overweight and obesity and may consume fewer fruits and vegetables compared to the general paediatric population. They are more likely to experience eating and drinking difficulties, restrictive eating, and mealtime behavioural challenges. The school environment is considered an ideal setting to improve CYP’s dietary intakes. The primary objective was to identify existing interventions to support healthier food choices for CYP attending specialist schools. Secondary objectives considered intervention development, fidelity and outcomes. Methods: A scoping review and narrative synthesis. Eligible studies were identified from bibliographic databases (e.g., Medline, Embase, PsychInfo) and grey literature (e.g., Clinicaltrials.gov, the Cochrane Library). A two-stage screening process was used. Intervention components were mapped according to the TIDieR-PHP and AACTT frameworks. Results: Seven studies, reported in ten records, were included. Interventions included modifications to the dining environment, sensory exploration, health promotion and social reinforcement. Interventions were implemented across the school day: lunchtime (n = 2), breaktime (n = 3) and other times (n = 2). Studies mainly focused on adolescents. There was some mixed evidence of increased consumption of fruits and vegetables, whole grains and water. Due to small sample sizes and heterogeneity, definitive conclusions are limited. A key finding is the lack of interventions to improve CYP’s food choices in specialist schools. Conclusions: This review highlights a crucial need for the development of multi-component interventions co-produced with stakeholders to promote healthy food choices and improve the dietary intakes of CYP attending specialist schools. Full article

Objective: Based on previous findings on the Lingguizhugan (LGZG)-mediated gut–liver axis, this study clarifies the therapeutic mechanisms of LGZG in metabolic dysfunction-associated steatotic liver disease (MASLD), with a focus on the gut microbiota–bile acid–TGR5 (GPBAR1) axis. Methods: C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks to induce MASLD, followed by 4-week LGZG intervention (21.57 g/kg/day, oral gavage). Metabolic phenotypes, gut microbiota (16S rRNA sequencing), serum/hepatic bile acids (targeted metabolomics), and molecular targets (qPCR/Western blot) were analyzed. Results: LGZG significantly alleviated HFD-induced obesity, insulin resistance, and hepatic steatosis, while enhancing whole-body energy expenditure (increased oxygen consumption (VO₂), and heat production (p < 0.05). It also reduced serum ALT (p < 0.001) and AST levels (p < 0.01). Mechanistically, LGZG remodeled the gut microbiota, specifically increasing Akkermansia, Bifidobacterium and Lachnospiraceae_NK4A236_group while decreasing Lactobacillus. This shift inhibited the intestinal FXR-Fgf15 axis, concurrently activating the hepatic alternative bile acid synthesis pathway (upregulating CYP27A1 and CYP7B1 protein expression; p < 0.001 and p < 0.01, respectively). Consequently, systemic accumulation of non-12α-hydroxylated bile acids (non-12-OH BAs) such as hyocholic acid (HCA) and 7-ketolithocholic acid (7-ketoLCA) occurred—known TGR5 agonists and intestinal FXR antagonists. These changes elevated serum GLP-1 levels (p < 0.05) and activated adipose TGR5-cAMP/PKA/CREB signaling. The metabolic benefits primarily originated from non-12-OH BAs enrichment and TGR5-mediated adipose browning, not hepatic FXR activation. Conclusions: Our findings show that LGZG ameliorates MASLD by remodeling bile acid profiles via intestinal FXR-Fgf15 axis inhibition and hepatic alternative synthesis pathway activation. This study highlights the TGR5-targeting properties of LGZG, providing a mechanistic basis for its therapeutic use in metabolic disorders. Full article

Background: Warfarin pharmacogenomics is critical due to its narrow therapeutic index and significant interpatient variability. While machine learning (ML) can predict anticoagulation control status (ACS), its “black-box” nature limits clinical translatability. Explainable Artificial Intelligence (XAI) addresses this by providing interpretable insights. This study applied ML and XAI to a warfarin pharmacogenomic dataset to predict poor ACS and explain model decisions. Methods: A post hoc analysis was conducted on a cross-sectional dataset of 232 patients receiving warfarin for ≥6 months. Data included age, gender, interacting drugs, SAMe-TT2R2 score, and genotypes for CYP2C9, VKORC1, and CYP4F2. Poor ACS was defined as time in therapeutic range (TTR) < 70%. The dataset was split into training (70%) and testing (30%) cohorts. Three models, Random Forest, XGBoost, and Logistic Regression, were developed and evaluated using AUC-ROC, sensitivity, and specificity. XAI techniques, including permutation importance and SHapley Additive exPlanations (SHAP), were employed for global and local interpretability. Results: Of 232 patients, 141 (60.8%) had poor ACS. XGBoost and Random Forest demonstrated comparable predictive accuracy (AUC-ROC: 0.67), outperforming Logistic Regression. Sensitivity was 0.83 and 0.79 for XGBoost and Random Forest, respectively. However, specificity was modest for both ensemble methods (Random Forest: 0.48; XGBoost: 0.41) and extremely low for Logistic Regression (0.04), indicating poor discrimination, particularly for identifying patients with adequate anticoagulation control. Globally, important predictors included the age, SAMe-TT2R2 score, CYP2C9 (*2/*2), female gender, and VKORC1 (C/T). XAI revealed predictions were primarily driven by VKORC1, CYP4F2, SAMe-TT2R2 scores, and drug interactions. Concordance between XAI predictions and actual ACS was 78% for adequate and 88.6% for poor ACS. SHAP analysis showed VKORC1 provided a stable risk signal (mean absolute SHAP: 1.44 ± 0.49 in concordant cases), while CYP2C9 was a high-variance, high-impact driver of discordance (mean SHAP: 3.44 ± 3.79 in discordant cases). Conclusions: ML models, particularly ensemble methods, show modest ability to predict poor warfarin control with limited ability to correctly identify patients with adequate control from our dataset. XAI transforms these models into interpretable tools, with SHAP analysis attributing predictions to specific genetic and clinical features. While predictive accuracy remains modest, this approach enhances transparency and provides a foundation for generating hypotheses that may ultimately support clinical decision-making in pharmacogenomic-guided warfarin therapy. Full article

Currently, most research on CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) gene editing in edible fungi focuses on monokaryotic strains. However, the biological mechanisms in a monokaryotic state often do not accurately reflect the actual physiological and metabolic conditions of dikaryotic strains. Therefore, this study used two mating-type-compatible monokaryotic strains, L1 and L2, isolated from Ganoderma lucidum ‘Hunong No.1’ G0119, and employed an RNP (ribonucleoprotein)-based CRISPR/Cas9 system to successfully knock out the cyp512a3 gene in strain L2, resulting in the edited strain L2-KO-cyp512a3. The strain was single-crossed with the previously edited L1 strain L1-KO-cyp512a3 in our laboratory to obtain a dikaryotic editing strain that was homozygous at the cyp512a3 locus, named G0119-KO-cyp512a3. UPLC-MS (Ultra Performance Liquid Chromatography–Mass Spectrometry) analysis showed that compared to the starting strain G0119, the dikaryotic editing strain exhibited varying degrees of reduction in the content of eight types of ganoderic acids, including ganoderic acid Me, ganoderic acid P, ganoderic acid T1, etc., with the reduction ranging from 30.5% to 80.1%. To further validate the function of cyp512a3, we overexpressed this gene in the L1 strain. The results showed that the contents of ganoderic acid Mk, ganoderic acid S, ganoderic acid T, and ganoderic acid R in the mycelium were 0.548 ± 0.020, 1.780 ± 0.028, 2.416 ± 0.148, and 0.281 ± 0.016 mg/g (dry weight), which were 1.5 times, 1.3 times, 1.3 times, and 1.3 times that of G0119, respectively. By integrating the results of gene knockout and overexpression, it can be clearly established that cyp512a3 is a key cytochrome P450 gene regulating the biosynthesis of ganoderic triterpenoids in Ganoderma lucidum. This study not only establishes, for the first time, a homologous recombination-based gene editing system in dikaryotic strains of Ganoderma lucidum, but also provides a research paradigm based on a dikaryon-editing tool for investigating key life traits of other edible fungi. Full article

Background/Objectives: Obesity is characterized by chronic low-grade inflammation, which plays a central role in the development of its metabolic complications. The genetic factors influencing this inflammatory phenotype remain incompletely understood. This study aimed to analyze the associations of functional polymorphisms in genes involved in extracellular matrix remodeling (MMP2, MMP9, MMP12, COL1A1), metabolism (MTHFR, CYP3A5), and vascular regulation (NOS3, AGTR1) with plasma cytokine profiles and to identify inflammatory subphenotypes in patients with obesity. Methods: The study included 127 individuals, comprising 73 patients with excess body weight (body mass index, BMI ≥ 25 kg/m²) and 54 individuals with normal weight (BMI 18.5–24.9 kg/m²). Genotyping of selected polymorphisms was performed using real-time PCR. Plasma concentrations of 47 cytokines and chemokines were measured by multiplex immunoassay. Results: Nominally significant associations between genetic variants and cytokine levels were identified. Polymorphisms COL1A1 rs1107946 (CA genotype) and MMP9 rs17576 (AG genotype) were associated with a favorable inflammatory profile (decreased IL-6 and increased IL-10, respectively). In contrast, the AGTR1 rs5186 (AC genotipe) variant was associated with elevated TNF-α, IP-10/CXCL10, while the MTHFR rs1801131 (AC genotipe) variant was linked to increased MIP-1β/CCL4, both reflecting a pro-inflammatory shift. Complex, pleiotropic associations were observed for MMP2 rs243865 (elevated IL-7 and Fractalkine/CX3CL1) and NOS3 rs1799983 (elevated MCP-1/CCL2 and Eotaxin/CCL11). Cluster analysis revealed distinct patient subpopulations with differing inflammatory signatures. In one well-defined subgroup, an exploratory model (test R² = 0.537) identified IL-8, IL-15, and albumin as candidate biomarkers predictive of BMI. Conclusions: The study identifies candidate genetic polymorphisms and inflammatory biomarkers associated with distinct patterns of systemic inflammation in obesity. These hypothesis-generating findings underscore the phenotypic heterogeneity of obesity and provide a basis for further research into the stratification of patients by the risk of developing metabolic complications. Full article

This study employed an artificial greenhouse-based system to enhance gonadal development in the Manila clam, Ruditapes philippinarum. The dynamics of gonadal development and expression patterns of five regulatory genes were analyzed through histological sections and quantitative PCR. Under the controlled conditions (Chlorophyll a: 18.61 ± 1.36 μg/L; temperature: 27.3 ± 2.0 °C), the clams’ gonads reached full maturity within approximately one month, underscoring the critical importance of appropriate food availability and temperature. Gene expression analysis revealed sex- and stage-specific patterns. The gonadotropin-releasing hormone (GnRH) gene was more expressed in males at day 7, reaching a significant peak at day 7. In contrast, females exhibited synchronized expression peaks for both estrogen-related receptor (ERR) and 17β-hydroxysteroid dehydrogenase (17β-HSD) at day 14 (p < 0.05). Cytochrome P450 17 (CYP17) exhibited a dynamic, sex-specific profile, with significantly higher levels in males at day 7 but elevated expression in females at day 14 and day 21. Furthermore, doublesex and mab-3-related transcription factor 4-like (Dmrt4-like) showed clear sex-dependent temporal patterns: it peaked early during maturation in males, while in females, the peak occurred significantly later, at day 21 (p < 0.05). These dynamic changes in gene expression were closely synchronized with histological alterations, providing mechanistic insights into the regulation of gonadal maturation in R. philippinarum. Full article

Drought stress induces pronounced metabolic and transcriptional reprogramming of glucosinolate (GLS) biosynthesis in Brassica oleracea. An integrative approach combining HPLC-based quantification of individual GLSs, quantitative real-time PCR of core biosynthetic and regulatory genes, correlation-based network analysis, and in silico promoter characterization was applied to evaluate drought responses across genetically diverse accessions. Drought triggered strong, accession-specific shifts in GLS composition, with sinigrin content increasing from 35.9% to 55.1% in BR1 and glucoerucin reaching up to 80.2% in CCP1, while indolic GLSs such as glucobrassicin and neoglucobrassicin accounted for >75% of total GLSs in CV2 and CCP3. Hierarchical clustering separated accessions into four distinct drought response clusters independent of morphotype. Correlation analysis revealed drought-induced rewiring of GLS interdependencies, characterized by strengthened positive associations among aliphatic GLSs (r > 0.75). Gene expression profiling identified conserved MYB-centered regulatory modules (MYB28, MYB29, MYB34, MYB122) alongside strong accession-specific induction of CYP79F1 (up to 6.3-fold), FMOGS-OX5 (up to 4.8-fold), and ST5a (up to 5.1-fold). Promoter analysis revealed enrichment of ABA- and stress-responsive cis-regulatory elements. These findings delineate a genotype-dependent regulatory framework underlying GLS plasticity and identify quantitative metabolic and transcriptional markers relevant for breeding drought-resilient Brassica cultivars. Full article

Personalized anesthesia has emerged as a key direction in modern perioperative medicine, driven by advances in molecular biology, analytical technologies, and digital monitoring. Traditional physiological parameters often fail to detect early stages of organ dysfunction, whereas molecular biomarkers provide earlier and more sensitive insight into inflammation, oxidative stress, neurotoxicity, and renal or hepatic injury. Inflammatory markers such as IL-6, CRP, and PCT indicate early immune activation, while oxidative stress biomarkers, including 8-isoprostanes and malondialdehyde, quantify metabolic imbalance and ischemia–reperfusion injury. Neurotoxicity biomarkers such as S100β, NSE, and GFAP allow early detection of subclinical cerebral injury, whereas kynurenine-pathway metabolites reflect neuroinflammation and the risk of postoperative cognitive dysfunction. Renal biomarkers such as NGAL, KIM-1, and cystatin C detect acute kidney injury significantly earlier than creatinine, and miR-122 holds strong potential as an early marker of hepatocellular injury. Genetic and epigenetic biomarkers—including polymorphisms in CYP2D6, CYP3A4/5, RYR1, OPRM1, and COMT, as well as microRNA-based signatures—enable individualized drug dosing and optimization of anesthetic strategies. Meanwhile, digital biomarkers such as EEG-derived indices, HRV, and NIRS provide continuous real-time physiological monitoring and can integrate with AI-based algorithms for predictive, adaptive anesthesia management. Although no single biomarker meets all criteria for an ideal clinical indicator, combining molecular, genetic, and digital biomarkers represents the most promising pathway toward fully personalized, safe, and outcome-optimized perioperative care. Full article

The colored-leaf Osmanthus fragrans is a valuable ornamental tree species that integrates greenery, colorful leaves, and fragrance. At present, research on colored-leaf Osmanthus fragrans mainly focuses on cultivar breeding, classification and cultivation, and physiological resistance, while studies on leaf color variation remain limited. In this study, the colored-leaf Osmanthus cultivar ‘Jinyu Guihua’ and its female parent were used as materials. The leaf coloration mechanism was systematically investigated through a combined analysis of physiology, transcriptomics, and metabolomics. The results showed that compared with the female parent, the leaves of ‘Jinyu Guihua’ exhibited significantly reduced chlorophyll b and anthocyanin contents, fewer chloroplasts, and more plastoglobules. Transcriptomic analysis identified 3938 differentially expressed genes (DEGs), among which the key chlorophyll metabolism gene CAO was downregulated and NOL was upregulated; the key carotenoid synthesis gene PSY was downregulated and CYP97A3 was upregulated; the key anthocyanin synthesis gene ANS was downregulated; and the PetC2 gene in the photosynthesis-related Cytb6-f complex was upregulated. qRT-PCR validation results were consistent with the RNA-seq data. Metabolomic analysis detected 1290 metabolites, classified into 21 subcategories, with flavonoids being the most abundant (17.21%). Anthocyanin synthase (ANS) significantly downregulated the expression levels of cyanidin-3-O-rutinoside (Cy3R) and delphinidin-3-O-rutinoside (De3R). In conclusion, the leaf color variation in ‘Jinyu Guihua’ is closely related to changes in leaf pigment content and the regulation of key metabolic pathway gene expression. The findings of this study provide a theoretical basis for the molecular breeding of new colored-leaf Osmanthus varieties and serve as a reference for trait research in other ornamental plants. Full article

Background/Objectives: Vedolizumab (VDZ), a monoclonal antibody targeting α4β7 integrin, is used in Crohn’s disease (CD) management, yet patients’ responses vary, underscoring the need for pharmacogenomic (PGx) markers. This study aimed to identify PGx pathways associated with suboptimal VDZ response using a rare-variant analytical framework. Methods: DNA from 63 CD patients treated with VDZ as first-line advanced therapy underwent whole-exome sequencing. Clinical response at week 14 classified patients as optimal responders (ORs) or suboptimal responders (SRs). Sequencing data were processed using GATK Best Practices, annotated with variant effect predictors, and filtered for rare damaging variants (damaging missense and high-confidence loss-of-function; minor allele frequency < 0.05). Variants were mapped to genes specific for SRs and ORs, and analyzed for pathway enrichment using the Reactome database. Rare-variant burden and composition differences were assessed with Fisher’s exact test and SKAT-O gene-set association analysis. Results: Suboptimal VDZ response was associated with pathways related to membrane transport (ABC-family proteins, ion channels), L1–ankyrin interactions, and bile acid recycling, while optimal response was associated with pathways involving MET signaling. SKAT-O identified lipid metabolism-related pathways as significantly different—SRs harbored variants in pro-inflammatory lipid signaling and immune cell trafficking genes (e.g., PIK3CG, CYP4F2, PLA2R1), whereas ORs carried variants in fatty acid oxidation and detoxification genes (e.g., ACADM, CYP1A1, ALDH3A2, DECR1, MMUT). Conclusions: This study underscores the potential of exome-based rare-variant analysis to stratify CD patients and guide precision medicine approaches. The identified genes and pathways are potential PGx markers for CD patients treated with VDZ. Full article

Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality worldwide. Despite therapeutic advances, prevention through dietary bioactives remains a promising strategy. The Annurca apple (Malus pumila Miller cv. Annurca), a Mediterranean food rich in chlorogenic acid, exhibits antioxidant and anti-inflammatory effects. This study evaluated, via molecular docking, the multi-target interaction profile of chlorogenic acid against key CRC-related proteins. Methods: The optimized 3D structure of chlorogenic acid was docked to ten protein targets implicated in CRC pathogenesis, using the GOLD v.2022.3.0 software. Validation of the docking protocol was achieved by re-docking native ligands (RMSD ≤ 2.0 Å). Binding affinities were assessed by ChemPLP scoring, and interaction networks were visualized in Maestro Schrödinger. Results: Chlorogenic acid displayed consistent binding across all evaluated targets (ChemPLP 57.12–69.66), showing the highest affinity for nAChR (69.66), CXCR2 (65.13), ERβ (63.18) and TGFBR2 (62.94). The ligand formed multiple hydrogen bonds and π-π stacking interactions involving Asp1040 (VEGFR-1), Cys919 (VEGFR-2), Lys320 (CXCR2), and Tyr195 residues (nAChR), contributing to strong complex stabilization. Interaction patterns in CYP19A1, ERβ, and ERRγ suggested potential modulation of hormonal and metabolic signaling. The compound also demonstrated stable binding to mTOR (60.01), indicating a possible inhibitory role in proliferative pathways. Collectively, these findings reveal a broad, polypharmacological binding profile involving angiogenic, inflammatory, and hormonal regulators. Conclusions: Chlorogenic acid acts as a promising multi-target ligand in CRC prevention, with our in silico evidence supporting its ability to modulate diverse oncogenic pathways. Further experimental studies are warranted to confirm its efficacy and translational potential. Full article

Background/Objectives: This review integrates evolutionary, metabolic, genetic, and nutritional perspectives to explain how sterol-derived vitamin D pathways shape human physiology and inter-individual variability in vitamin D status. Methods: The literature on sterol and vitamin D metabolism across animals, plants, fungi, and algae was synthesized with data from metabolomics databases, genome-wide association studies, RNA-seq resources (including GTEx), structural biology, and functional genomics. Results: Vitamin D₂ and vitamin D₃ likely emerged early in evolution as non-enzymatic photochemical sterol derivatives and were later co-opted into a tightly regulated endocrine system in vertebrates. In humans, cytochrome P450 enzymes coordinate vitamin D activation and degradation and intersect with oxysterol production, thereby linking vitamin D signaling to cholesterol and bile acid metabolism. Tissue-specific gene expression and regulatory genetic variants, particularly in the genes DHCR7, CYP2R1, CYP27B1, and CYP27A1, contribute to population-level differences in vitamin D status and metabolic outcomes. Structural analyses reveal selective, high-affinity binding of 1,25-dihydroxyvitamin D₃ to VDR, contrasted with broader, lower-affinity ligand recognition by LXRs. Dietary patterns modulate nuclear receptor signaling through distinct yet convergent ligand sources, including cholesterol-derived oxysterols, oxidized phytosterols, and vitamin D₂ versus vitamin D₃. Conclusions: Sterol and vitamin D metabolism constitute an evolutionarily conserved, adaptable network shaped by UV exposure, enzymatic control, genetic variation, and diet. This framework explains inter-individual variability in vitamin D biology and illustrates how evolutionary and dietary modulation of sterol-derived ligands confers functional flexibility to nuclear receptor signaling in human health. Full article

Background: Depression and diabetic neuropathy (DN) commonly complicate diabetes and impair glycemic control and quality of life. Ketamine and its S-enantiomer, esketamine, provide rapid antidepressant and analgesic effects, yet diabetes-related pathophysiology and co-therapies may modify exposure, response, and safety. Methods: We conducted a scoping review following PRISMA-ScR. MEDLINE/PubMed, CINAHL, and APA PsycInfo were searched (January 2020–31 May 2025). Eligible human and animal studies evaluated ketamine, esketamine, or norketamine in the context of diabetes (type 1 [T1DM], type 2 [T2DM], gestational [GDM]), or DN, and reported psychiatric, analgesic, metabolic, or mechanistic outcomes. Two reviewers independently screened and charted data; no formal risk-of-bias assessment was performed. Results: Eleven studies met inclusion criteria: four human case reports/series (three T1DM, one T2DM), one randomized trial in GDM, two narrative reviews of topical ketamine for DN, and four preclinical rodent studies using streptozotocin- or diet-induced diabetes models. Short-term improvements were reported for treatment-resistant depression and neuropathic pain, including opioid-sparing postoperative analgesia in GDM. Glycemic effects varied across settings, with both hyperglycemia and hypoglycemia reported. Mechanistic and clinical drug–drug and drug-disease interactions (particularly involving metformin, GLP-1 receptor agonists, SGLT2 inhibitors, and CYP3A4/CYP2B6 modulators) remain insufficiently studied. We outline a forward-looking population pharmacokinetic (popPK) and pharmacokinetic-pharmacodynamic (PK-PD) research agenda, including priority covariates (eGFR, hepatic function, inflammatory status, HbA1c, genotype, co-medications) and sparse-sampling windows for future model-informed precision dosing. Conclusions: Current evidence supports cautious, selective use of ketamine for refractory depression and DN within multidisciplinary diabetes care. Purpose-built popPK/PK-PD studies in both human and preclinical diabetic models cohorts are needed to quantify variability, define drug–disease–drug interactions and glycemic risk, and inform individualized dosing strategies. Full article

Cervical cancer (CC) remains a common malignant tumor that seriously threatens women’s health globally. Gramine (GR), a natural alkaloid derived from plants such as Arundo donax L., exhibits anti-tumor activities, yet its mechanistic actions in CC are still unclear. Here, we integrated cell-based assays, network pharmacology, and multi-omics analysis to systematically investigate the molecular mechanisms underlying GR’s anti-CC effects. In vitro experiments showed that GR significantly inhibited proliferation and migration, induced apoptosis, and triggered G₀/G₁ phase cell cycle arrest in HeLa cells. Integrated multi-omics analysis identified CDK2 as a critical target of GR, with both mRNA and protein levels markedly reduced following treatment. Mechanistically, GR likely suppresses CC progression by modulating the “CYP4A22-AS1/LINC00958–hsa-miR-133b–CDK2” competitive endogenous RNA (ceRNA) axis. Immune analysis indicated positive correlations of CDK2, CYP4A22-AS1, and LINC00958 with the immune checkpoint molecule CD47. Collectively, our findings demonstrate that GR inhibits CC through a ncRNA-mediated suppression of CDK2, leading to reduced HeLa cell proliferation and migration and enhanced apoptosis. These results provide a mechanistic rationale for developing GR as a candidate agent for targeted therapy and immuno-combination strategies in CC. Full article

Desulfovibrio (DSV), sulfate-reducing gut bacteria that generate hydrogen sulfide (H₂S), can impact host health through diverse mechanisms including bile acid (BA) metabolism. Although intestinal overgrowth of DSV expands the BA pool and promotes liver injury, its causal role in hepatic pathophysiology remains incompletely defined. Here, by employing complementary interventions of cholic acid (CA) supplementation and the BA sequestrant cholestyramine in mouse models, we show that DSV-driven liver injury is mediated by aberrant BA metabolism coupled with gut microbial remodeling. CA alone induced overt hepatic damage, whereas supplemental DSV did not further exacerbate injury caused by excessive CA. Intervention with the BA sequestrant cholestyramine markedly attenuated DSV-elicited hepatic inflammatory and histological alterations, which were associated with an upregulation of the intestinal BAs pool. Hepatic expression of BAs synthetic genes Cyp7a1 and Cyp8b1 verified a negative-feedback regulation of BA metabolism upon treatments. 16S rRNA gene sequencing revealed that CA, DSV, and the cholestyramine all significantly influenced the gut microbiota. CA reduced microbial richness and drove community separation, while DSV intervention under high BA conditions enriched specific biomarkers including Eubacterium ventriosum and Enterorhabdus. Notably, the administration of cholestyramine attenuated these DSV-associated microbial shifts and further reduced overall species richness, confirming the integral role of BA dynamics in shaping the gut microbial community. Collectively, our research reveals the intricate link between DSV, BAs, and gut microbiota in liver injury, and suggests that modulation of BAs may hold therapeutic potential for DSV-associated liver hepatic conditions. Full article