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

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 inv...

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Published in:NPJ biofilms and microbiomes 2023-11, Vol.9 (1), p.84-84, Article 84
Main Authors: Yang, Xinyue, Zhang, Meihong, Liu, Yan, Wei, Fuxiao, Li, Xin, Feng, Yuqing, Jin, Xiaolu, Liu, Dan, Guo, Yuming, Hu, Yongfei
Format: Article
Language:English
Subjects:
631/326/2565/2134
631/326/41/2142
Animals
Biomedical and Life Sciences
Chickens
Fatty liver
Female
Gene expression
High fat diet
Intestinal microflora
Inulin
Inulin - pharmacology
Inulin - therapeutic use
Life Sciences
Liver diseases
Medical Microbiology
Megamonas
Metabolism
Mice
Microbial Ecology
Microbial Genetics and Genomics
Microbiology
Non-alcoholic Fatty Liver Disease - drug therapy
Non-alcoholic Fatty Liver Disease - genetics
Non-alcoholic Fatty Liver Disease - metabolism
Oral administration
Probiotics
Propionates
Propionic acid
Signal transduction
Steatosis
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Summary: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.
ISSN:2055-5008
2055-5008
DOI:10.1038/s41522-023-00451-y