AUTHOR=Song Lini , Ji Wenyi , Cao Xi 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1404678

DOI=10.3389/fcimb.2024.1404678

ISSN=2235-2988

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>We adopted a combinatory approach of metabolomics and fecal 16S rRNA analysis to investigate gut microbiota and metabolite in two different mouse models, <italic>ACE2</italic> knockout (<italic>ACE2</italic> KO) mice and the ACE2-overexpressing obese mice.</p></sec><sec><title>Results</title><p>16S rRNA gene sequencing revealed that ACE2 influences microbial community composition and function, and ACE2 KO mice had increased <italic>Deferribacteres</italic>, <italic>Alcaligenaceae</italic>, <italic>Parasutterella</italic>, <italic>Catenibacterium</italic>, and <italic>Anaerotruncus</italic>, with decreased short-chain fatty acid (SCFA)-producing bacteria (<italic>Marvinbryantia</italic> and <italic>Alistipes</italic>). In contrast, ACE2-overexpressed mice exhibited increased anti-inflammatory probiotic (<italic>Oscillospiraceae</italic>, <italic>Marinifilaceae</italic>, and <italic>Bifidobacteriaceae</italic>) and SCFA-producing microbes (<italic>Rikenellaceae, Muribaculaceae</italic>, <italic>Ruminococcaceae</italic>, <italic>Odoribacter</italic>, and <italic>Alistipes</italic>) and decreased <italic>Firmicutes/Bacteroidetes</italic>, <italic>Lactobacillaceae</italic>, <italic>Erysipelotrichaceae</italic>, and <italic>Lachnospiraceae</italic>. Metabolome analysis indicated differential metabolites in <italic>ACE2</italic> 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.</p></sec><sec><title>Conclusion</title><p>Our study confirms for the first time a significant association between <italic>ACE2</italic> status and gut microbiome and metabolome profiles, providing a novel mechanism for the positive effect of ACE2 on energy homeostasis.</p></sec>