Specific Strains of Faecalibacterium prausnitzii Ameliorate Nonalcoholic Fatty Liver Disease in Mice in Association with Gut Microbiota Regulation

Abstract

Evidence linking <i>Faecalibacterium prausnitzii</i> abundance to nonalcoholic fatty liver disease (NAFLD) is accumulating; however, the causal relationship remains obscure. In this study, 12 <i>F. prausnitzii</i> strains were orally administered to high fat diet fed C57BL/6J mice for 12 weeks to evaluate the protective effects of <i>F. prausnitzii</i> on NAFLD. We found that five <i>F. prausnitzii</i> strains, A2-165, LB8, ZF21, PL45, and LC49, significantly restored serum lipid profiles and ameliorated glucose intolerance, adipose tissue dysfunction, hepatic steatosis, inflammation, and oxidative stress in a mouse model of NAFLD. Moreover, two strains, LC49 and LB8, significantly enhanced short-chain fatty acid (SCFA) production and modulated the gut microbiota. Based on the combined analysis of linear discriminant analysis effect size and microbial communities, the core microbiome related to NAFLD comprised <i>Odoribacter</i>, <i>Roseburia</i>, <i>Erysipelatoclostridium</i>, <i>Tyzzerella</i>, <i>Faecalibaculum</i>, <i>Blautia</i>, and <i>Acetatifactor</i>, and the last five genera can be reversed by treatment with the LC49 and LB8 strains. Additionally, the LC49 and LB8 strains enriched <i>Lactobacillus</i>, <i>Ileibacterium</i>, <i>Faecalibacterium</i>, <i>Dubosiella</i>, and <i>Bifidobacterium</i> and downregulated pathways involving carbohydrate metabolism, amino acid metabolism, and fatty acid biosynthesis. Interestingly, LC49 supplementation also upregulated tryptophan metabolism, glutathione metabolism, and valine, leucine, and isoleucine degradation, which might be related to NAFLD prevention. Collectively, <i>F. prausnitzii</i> LC49 and LB8 exerted considerable anti-NAFLD and microbiota-regulating effects, indicating their potential as probiotic agents for NAFLD treatment.