Accumulated evidence supports the beneficial role of inulin in alleviating metabolic dysfunction-associated fatty liver disease (MAFLD) by modulating gut microbiota. However, the underlying mechanisms are not fully understood. Here we used high-fat diet (HFD)-induced laying hen model of MAFLD to investigate the effect of inulin on ameliorating MAFLD and found that the inulin-enriched Megamonas genus was inversely correlated with hepatic steatosis-related parameters. Oral administration of a newly isolated commensal bacterium by culturomics, M. funiformis CML154, to HFD-fed hens and mice ameliorated MAFLD, changed liver gene expression profiles, and increased intestinal propionate concentration. Further evidence demonstrated that the anti-MAFLD effect of M. funiformis CML154 is attributed to propionate-mediated activation of the APN-AMPK-PPARα signaling pathway, thereby inhibiting fatty acid de novo synthesis and promoting β-oxidation. These findings establish the causal relationships among inulin, M. funiformis, and MAFLD, and suggest that M. funiformis CML154 is a probiotic candidate for preventative or therapeutic intervention of MAFLD.

累积的证据支持菊粉通过调节肠道微生物群来缓解代谢功能障碍相关的脂肪肝疾病 (MAFLD) 的有益作用。然而，其根本机制尚未完全了解。在这里，我们使用高脂饮食（HFD）诱导的MAFLD蛋鸡模型来研究菊粉对改善MAFLD的作用，发现富含菊粉的巨单胞菌属与肝脂肪变性相关参数呈负相关。通过培养组学新分离出的共生细菌M. funiformis CML154 给 HFD 喂养的母鸡和小鼠口服，可以改善 MAFLD，改变肝脏基因表达谱，并增加肠道丙酸浓度。进一步的证据表明， M. funiformis CML154的抗MAFLD作用归因于丙酸介导的APN - AMPK - PPARα信号通路的激活，从而抑制脂肪酸从头合成并促进β-氧化。这些发现确立了菊粉、绳形微球菌和 MAFLD之间的因果关系，并表明绳状微球菌CML154 是用于预防或治疗干预 MAFLD 的益生菌候选者。