Desulfovibrio vulgaris, a potent acetic acid-producing bacterium, attenuates nonalcoholic fatty liver disease in mice

Abstract

The emerging evidence supports the use of prebiotics like herb-derived polysaccharides for treating nonalcoholic fatty liver disease (NAFLD) by modulating gut microbiome. The present study was initiated on the microbiota-dependent anti-NAFLD effect of <i>Astragalus</i> polysaccharides (APS) extracted from <i>Astragalus mongholicus</i> Bunge in high-fat diet (HFD)-fed mice. However, the exact mechanisms underlying the beneficial effects of APS on NAFLD formation remain poorly understood.Co-housing experiment was used to assess the microbiota dependent anti-NAFLD effect of APS. Then, targeted metabolomics and metagenomics were adopted for determining short-chain fatty acids (SCFAs) and bacteria that were specifically enriched by APS. Further <i>in vitro</i> experiment was carried out to test the capacity of SCFAs-producing of identified bacterium. Finally, the anti-NAFLD efficacy of identified bacterium was tested in HFD-fed mice.Our results first demonstrated the anti-NAFLD effect of APS in HFD-fed mice and the contribution of gut microbiota. Moreover, our results indicated that SCFAs, predominantly acetic acid were elevated in APS-supplemented mice and <i>ex vivo</i> experiment. Metagenomics revealed that <i>D. vulgaris</i> from <i>Desulfovibrio</i> genus was not only enriched by APS, but also a potent generator of acetic acid, which showed significant anti-NAFLD effects in HFD-fed mice. In addition, <i>D. vulgaris</i> modulated the hepatic gene expression pattern of lipids metabolism, particularly suppressed hepatic fatty acid synthase (FASN) and CD36 protein expression.Our results demonstrate that APS enriched <i>D. vulgaris</i> is effective on attenuating hepatic steatosis possibly through producing acetic acid, and modulation on hepatic lipids metabolism in mice. Further studies are warranted to explore the long-term impacts of <i>D. vulgaris</i> on host metabolism and the underlying mechanism.