《生命科学》 2026, 38(5): 891-904
运动调控肠道菌群及代谢物改善代谢功能障碍相关脂肪性肝病的研究进展
摘 要：
代谢功能障碍相关脂肪性肝病（metabolic dysfunction-associated fatty liver disease, MAFLD）目前已成为全球范围内常见的慢性肝病，其发病机制与肠道菌群（GM）失调和代谢产物紊乱密切相关，具体包括脂多糖（LPS）水平升高、短链脂肪酸（SCFA）生成减少，以及胆汁酸（BAs）代谢异常。这些代谢紊乱通过肠-肝轴加重肝脏葡萄糖、脂质代谢异常与炎症反应，进而推动MAFLD向脂肪性肝炎、肝纤维化甚至肝细胞癌进展。目前尚无药物能够完全治愈该疾病，科学运动与健康饮食是改善MAFLD的重要非药物策略。运动干预可通过调节GM组成，降低LPS水平，增加SCFA生成，维持BAs稳态，通过肠-肝轴调控肝脏组织能量代谢，改善MAFLD的病理进展。本文系统综述“运动-肠道菌群-菌群代谢物-肝脏轴”在改善MAFLD中的作用机制，并探讨运动联合益生菌、多糖等新型治疗方法的潜力，以期为MAFLD患者的微生物群精准干预与个性化运动处方的制定提供理论依据。
通讯作者：沈文清 , Email:GraceShen07@163.com
Abstract:
Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as a common chronic liver diseaseworldwide, and its pathogenesis is closely associated with gut microbiota (GM) dysbiosis and metabolic product disorders, including elevated lipopolysaccharide (LPS) levels, reduced short-chain fatty acids (SCFA) production, and abnormal bile acids (BAs) metabolism. These metabolic disturbances aggravate abnormalities in hepatic glucose and lipid metabolism as well as inflammatory responses via the “gut-liver axis”, thereby promoting the progression of MAFLD to steatohepatitis, liver fibrosis, and even hepatocellular carcinoma. Currently, no specific pharmacotherapy is available for the complete cure of MAFLD, and lifestyle interventions, including structured exercise and dietary interventions, remain the primary approaches for improving and treating MAFLD. This review systematically elaborates on how exercise ameliorates MAFLD via the “exercise-gut microbiota-microbial metabolites-liver tissue” axis. Studies have shown that MAFLD patients commonly exhibit gut microbiota dysbiosis, characterized by an increased Firmicutes/Bacteroidetes (F/B) ratio, reduced beneficial bacteria (e.g., Akkermansia muciniphila, Faecalibacterium prausnitzii), and increased pathogenic bacteria (e.g., Prevotella, Streptococcus). Gut microbiota dysbiosis leads to elevated lipopolysaccharide (LPS) production, disrupted intestinal barrier function, and induced metabolic endotoxemia. Concurrently, exercise suppresses the production of short-chain fatty acids (SCFAs), particularly butyrate, thereby impairing the protective effects of SCFAs on intestinal barrier integrity, antiinflammatory actions, and metabolic regulation. Aberrant bile acid (BA) metabolism manifests as excessive accumulation of primary BAs and reduced conversion to secondary BAs, further aggravating liver tissue injury. Exercise effectively remodels the composition, structure, and function of the gut microbiota, with the beneficial effects being influenced by exercise modality, intensity, volume, and individual differences. Studies indicate that both endurance exercise (EE) and high intensity interval training (HIIT), among other exercise modalities, modulate gut microbiota composition, notably increasing beneficial bacteria such as Bacteroidetes and Actinobacteria, and significantly lowering the F/B ratio in obese patients, thereby improving microbial diversity. Exercise induces beneficial alterations in the gut microbiota and subsequently modulates microbial metabolites: 1) It enhances SCFA (acetate, propionate, butyrate) production, which in turn suppresses inflammatory responses, improves insulin sensitivity, and strengthens intestinal barrier function via activation of G protein coupled receptors (e.g., FFAR3, formerly GPR41, and FFAR2, formerly GPR43), thereby regulating hepatic lipid metabolism. 2) It modulates BA metabolism, characterized by a significant increase in secondary BAs such as lithocholic acid (LCA), activation of the farnesoid X receptor (FXR)/takeda G protein coupled receptor 5 (TGR5) metabolic axis, promotion of cholesterol catabolism, amelioration of glucose and lipid metabolism, and inhibition of hepatic fat accumulation. 3) It reduces circulating LPS levels and alleviates endotoxemia. Furthermore, exercise directly improves intestinal barrier function by upregulating the expression of tight junction proteins (e.g., zonula occludens 1, ZO1; occludin), thereby inhibiting the translocation of harmful substances such as LPS to the liver. Additional studies suggest that exercise combined with dietary interventions such as probiotics (e.g., Lactobacillus rhamnosus) or dietary polysaccharides (e.g., Lycium barbarum polysaccharide) effectively improves gut microbiota composition and function, intestinal barrier integrity, and hepatic inflammatory responses, providing novel strategies for the prevention and treatment of MAFLD. In summary, exercise, as a safe, economical, and efficient nonpharmacological intervention, effectively ameliorates the pathophysiological progression of MAFLD through multitarget regulation of the composition and function of the gut microbiota and its metabolites. Future research should focus on establishing optimized exercise
prescriptions for different populations (e.g., based on age, sex, disease stage, etc.) to improve MAFLD. Moreover, further exploration is warranted into the molecular mechanisms and clinical drug development of exercise combined with dietary interventions such as prebiotics, probiotics, and nutritional supplements, to develop personalized and precise strategies for the prevention and treatment of MAFLD.
Communication Author：SHEN Wen-Qing , Email:GraceShen07@163.com
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