Inulin-enriched Megamonas funiformis ameliorates metabolic dysfunction-associated fatty liver disease by producing propionic acid

Author:

Yang Xinyue,Zhang Meihong,Liu Yan,Wei Fuxiao,Li Xin,Feng Yuqing,Jin Xiaolu,Liu Dan,Guo Yuming,Hu YongfeiORCID

Abstract

AbstractAccumulated 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.

Funder

Natural Science Foundation of Beijing Municipality

National Natural Science Foundation of China

Publisher

Springer Science and Business Media LLC

Subject

Applied Microbiology and Biotechnology,Microbiology,Biotechnology

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