■经典肾素-血管紧张素系统(RAS)的异常激活和肠道微生态失调对胰岛素抵抗(IR)产生不利影响,血脂异常,和其他代谢综合征标志物。然而,血管紧张素转换酶2(ACE2)和肠道健康在全身稳态中的作用各不相同,它们的相互作用还没有被完全理解。
■我们采用了代谢组学和粪便16SrRNA分析的组合方法来研究两种不同小鼠模型中的肠道微生物群和代谢物,ACE2敲除(ACE2KO)小鼠和ACE2过表达的肥胖小鼠。
■16SrRNA基因测序显示ACE2影响微生物群落组成和功能,ACE2KO小鼠的去铁杆菌增加,alcaligenaceae,Parasutterilla,副杆菌属,和anaerotruncus,产生短链脂肪酸(SCFA)的细菌(Marvinbryantia和Alistipes)减少。相比之下,ACE2过表达的小鼠表现出增加的抗炎益生菌(Oscillospiraceae,Marinifilaceae,和双歧杆菌科)和产生SCFA的微生物(Rikenellaceae,Muribaculaceae,Ruminocycaceae,Odoribacter,和Alistipes)和减少的Firmicutes/拟杆菌,乳酸杆菌科,Erysipelotricaceae,和落叶松科。代谢组分析表明ACE2KO和ACE2过表达小鼠的代谢产物差异,尤其是与糖脂代谢相关的化合物.此外,肠道菌群与代谢产物之间的相关性分析显示出影响宿主健康的动态相互影响。
■我们的研究首次证实了ACE2状态与肠道微生物组和代谢组之间的显著关联,为ACE2对能量稳态的积极作用提供了新的机制。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.