Integrated analysis of gut microbiome and its metabolites in ACE2-knockout and ACE2-overexpressed mice.

BACKGROUND

Aberrant activation of the classic renin-angiotensin system (RAS) and intestinal micro dysbiosis adversely affect insulin resistance (IR), dyslipidemia, and other metabolic syndrome markers. However, the action of angiotensin-converting enzyme 2 (ACE2) and gut health in systemic homeostasis vary, and their interaction is not completely understood.

METHODS

We adopted a combinatory approach of metabolomics and fecal 16S rRNA analysis to investigate gut microbiota and metabolite in two different mouse models, knockout ( KO) mice and the ACE2-overexpressing obese mice.

RESULTS

16S rRNA gene sequencing revealed that ACE2 influences microbial community composition and function, and ACE2 KO mice had increased , , , , and , with decreased short-chain fatty acid (SCFA)-producing bacteria ( and ). In contrast, ACE2-overexpressed mice exhibited increased anti-inflammatory probiotic (, , and ) and SCFA-producing microbes (, , , and ) and decreased , , , and . Metabolome analysis indicated differential metabolites in KO and ACE2-overexpression mice, especially the glucolipid metabolism-related compounds. Furthermore, correlation analysis between gut microbiota and metabolites showed a dynamic mutual influence affecting host health.

CONCLUSION

Our study confirms for the first time a significant association between status and gut microbiome and metabolome profiles, providing a novel mechanism for the positive effect of ACE2 on energy homeostasis.