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, ACE2 knockout ( ACE2 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 Deferribacteres , Alcaligenaceae , Parasutterella , Catenibacterium , and Anaerotruncus , with decreased short-chain fatty acid (SCFA)-producing bacteria ( Marvinbryantia and Alistipes ). In contrast, ACE2-overexpressed mice exhibited increased anti-inflammatory probiotic ( Oscillospiraceae , Marinifilaceae , and Bifidobacteriaceae ) and SCFA-producing microbes ( Rikenellaceae, Muribaculaceae , Ruminococcaceae , Odoribacter , and Alistipes ) and decreased Firmicutes/Bacteroidetes , Lactobacillaceae , Erysipelotrichaceae , and Lachnospiraceae . Metabolome analysis indicated differential metabolites in ACE2 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 ACE2 status and gut microbiome and metabolome profiles, providing a novel mechanism for the positive effect of ACE2 on energy homeostasis.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Song, Ji and Cao.)