Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a critical global health burden, driven by rising prevalence rates and earlier disease onset. Current therapeutic strategies remain limited to lifestyle interventions, with no approved pharmacotherapies targeting disease progression. Growing evidence highlights gut microbiota dysbiosis as a pivotal contributor to MASLD pathogenesis, characterized by disrupted intestinal barrier function, endotoxin translocation, and dysregulated bile acid (BA) and short-chain fatty acid (SCFA) metabolism. Preclinical studies suggest that specific botanical drugs and standardized polyherbal formulations may mitigate MASLD through microbiota modulation.Methods: A systematic review of preclinical and clinical studies (2015–2025) was conducted across PubMed, Web of Science, and CNKI. Search terms included “gut microbiota,” “Traditional Chinese Medicine (TCM),” and “MASLD,” focusing on studies with chemically defined botanical metabolites (purity >90%) or rigorously characterized polyherbal formulations. Exclusion criteria eliminated reports lacking microbial taxonomic validation (e.g., 16S rRNA sequencing), dose-response relationships, or mechanistic validation in animal models.Results: The synthesis of studies reveals that TCM ameliorates MASLD through three interconnected mechanisms: restoration of gut microbial diversity, reinforcement of intestinal barrier integrity via tight junction protein upregulation (e.g., ZO-1 and occludin), and normalization of BA/SCFA metabolism. Among the 10 botanical drugs and 11 formulations reviewed, significant reduction in liver steatosis were shown in rodent models. However, only 4% of these interventions progressed to human trials, and critical methodological inconsistencies were observed, including inconsistent phytochemical standardization and overreliance on homogeneous animal models (68% using male C57BL/6 mice).Conclusion: While TCM shows promise in modulating microbiota-liver crosstalk, clinical translation is hindered by insufficient phytochemical standardization, unvalidated multi-component synergies, and a paucity of human efficacy data. To bridge this gap, future research must prioritize randomized controlled trials with liver histology endpoints, ConPhyMP-guided quality control protocols, and humanized microbiota models. Rigorous validation of TCM’s microbiota-centric mechanisms—rather than empirical applications—will be essential to advance these interventions into clinically actionable therapies for MASLD.

Objective: Yinchenhao decoction (YCHD), a classical herbal formula comprising Artemisia capillaris, Gardenia jasminoides, and Rheum palmatum, has been clinically used for over 1000 years to treat cholestasis. However, its mechanism of action remains undefined. This study aimed to elucidate YCHD’s therapeutic mechanisms against cholestasis, with a focus on the gut microbiota-mediated regulation of the farnesoid X receptor (FXR)–fibroblast growth factor 15 (FGF15) pathway. Methods: An alpha-naphthyl isothiocyanate (ANIT)-induced cholestasis mouse model was established. Mice received YCHD (3/9 g/kg) for 7 days. 16S rRNA sequencing, targeted LC/MS (bile acid (BA) quantification), untargeted GC/MS (fecal metabolite detection), qPCR/Western blot (FXR pathway analysis), fecal microbiota transplantation (FMT), and antibiotic depletion were employed to dissect the gut–liver axis interactions. Results: YCHD alleviated cholestatic liver injury by reducing serum biomarkers, restoring BA homeostasis via FXR-FGF15 activation, and suppressing hepatic Cyp7a1-mediated BA synthesis. It remodeled gut microbiota, enriched FXR-activating secondary BAs (CDCA, DCA, CA), and restored the intestinal barrier integrity. Antibiotic cocktail abolished YCHD’s efficacy, while FMT from YCHD-treated mice enhanced its therapeutic effects, confirming microbiota dependency. Conclusions: YCHD mitigates cholestasis through gut microbiota-driven FXR activation and direct hepatobiliary regulation. These findings bridge traditional medicine and modern pharmacology, highlighting microbiome modulation as a therapeutic strategy for cholestatic liver diseases.

Gastric cancer is one of the most prevalent gastrointestinal malignancies worldwide, with Helicobacter pylori infection, host genetic susceptibility and environmental exposure serving as major driving risk factors. Accumulating studies have demonstrated that host genetics, the microbiome and epigenetic modifications collectively govern gastric cancer initiation and progression. These three components form a bidirectional regulatory axis: host genetic profiles and epigenetic remodeling shape the composition of endogenous microbial communities, while the microbiome and its metabolites trigger epigenetic reprogramming to modulate transcription of oncogenes and tumor suppressors. Deciphering this intricate tripartite regulatory network holds great potential to facilitate the development of precise therapeutic interventions for gastric cancer. This review delineates the respective roles of host genetics, the microbiome and epigenetic modifications throughout gastric cancer evolution and summarizes corresponding prospective intervention strategies. We elaborate on the reciprocal interplay between the microbiome and host genetic/epigenetic factors, and highlight the vital clinical significance of this crosstalk for gastric cancer prevention and treatment.