OBJECTIVE Although the underlying mechanism is largely unknown, gut
dysbiosis has emerged as a central initiator of
obesity-related
diseases including
nonalcoholic fatty liver disease (
NAFLD),
type 2 diabetes and meta?bolic
syndrome. The emerging evidence support the use of
prebiotics like herb-derived
polysaccharides for treating
NAFLD by modulating
gut microbiome. So, our study focused on the
microbiota-dependent anti-
NAFLD effect and the exact mechanisms of Astragalus
polysaccharides (APS) extracted from
Astragalus mongholicus Bunge in
high-fat diet (HFD) fed
mice.
METHODS 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
in vitro 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. RESULTS 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 ex vivo experiment.
Metagenomics revealed that D. vulgaris from
Desulfovibrio 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, D. vulgaris modulated the hepatic
gene expression pattern of
lipids metabolism, particularly suppressed hepatic
fatty acid synthase (FASN) and
CD36 protein expression. CONCLUSION APS enriched D. vulgaris 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 D. vulgaris on host
metabolism and the underly?ing mechanism.