Zhou Ting, Jin Ziwen, Jiang Rilei, Li Weiwei
School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Pharmacol. 2025 Jun 10;16:1600439. doi: 10.3389/fphar.2025.1600439. eCollection 2025.
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.
背景:代谢功能障碍相关脂肪性肝病(MASLD)已成为一项严峻的全球健康负担,这是由其患病率上升和发病年龄提前所驱动的。目前的治疗策略仍局限于生活方式干预,尚无针对疾病进展的获批药物疗法。越来越多的证据表明,肠道微生物群失调是MASLD发病机制的关键因素,其特征为肠道屏障功能破坏、内毒素易位以及胆汁酸(BA)和短链脂肪酸(SCFA)代谢失调。临床前研究表明,特定的植物药和标准化的多草药配方可能通过调节微生物群来减轻MASLD。 方法:对2015年至2025年期间发表在PubMed、Web of Science和CNKI上的临床前和临床研究进行了系统综述。检索词包括“肠道微生物群”、“中药(TCM)”和“MASLD”,重点关注具有化学定义的植物代谢物(纯度>90%)或经过严格表征的多草药配方的研究。排除标准排除了缺乏微生物分类学验证(如16S rRNA测序)、剂量反应关系或动物模型中机制验证的报告。 结果:研究综合表明,中药通过三种相互关联的机制改善MASLD:恢复肠道微生物多样性、通过上调紧密连接蛋白(如ZO-1和闭合蛋白)增强肠道屏障完整性以及使BA/SCFA代谢正常化。在审查的10种植物药和11种配方中,啮齿动物模型显示肝脏脂肪变性显著减少。然而,这些干预措施中只有4%进入了人体试验,并且观察到了关键的方法学不一致性,包括植物化学标准化不一致以及过度依赖同质动物模型(68%使用雄性C57BL/6小鼠)。 结论:虽然中药在调节微生物群与肝脏的相互作用方面显示出前景,但临床转化受到植物化学标准化不足、未经验证的多成分协同作用以及人体疗效数据匮乏的阻碍。为了弥补这一差距,未来的研究必须优先开展以肝脏组织学为终点的随机对照试验、采用ConPhyMP指导的质量控制方案以及人源化微生物群模型。对中药以微生物群为中心的机制进行严格验证而非经验性应用,对于将这些干预措施推进为MASLD的临床可行疗法至关重要。
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