Impact of the gut microbiota on angiotensin II-related disorders and its mechanisms

The renin-angiotensin system (RAS) consists of multiple angiotensin peptides and performs various biological functions mediated by distinct receptors. Angiotensin II (Ang II) is the major effector of the RAS and affects the occurrence and development of inflammation, diabetes mellitus and its complications, hypertension, and endorgan damage via the Ang II type 1 receptor. Recently, considerable interest has been given to the association and interaction between the gut microbiota and host. Increasing evidence suggests that the gut microbiota may contribute to cardiovascular diseases, obesity, type 2 diabetes mellitus, chronic inflammatory diseases, and chronic kidney disease. Recent data have confirmed that Ang II can induce an imbalance in the intestinal flora and further aggravate disease progression. Furthermore, angiotensin converting enzyme 2 is another player in RAS, alleviates the deleterious effects of Ang II, modulates gut microbial dysbiosis, local and systemic immune responses associated with coronavirus disease 19. Due to the complicated etiology of pathologies, the precise mechanisms that link disease processes with specific characteristics of the gut microbiota remain obscure. This review aims to highlight the complex interactions between the gut microbiota and its metabolites in Ang IIrelated disease progression, and summarize the possible mechanisms. Deciphering these mechanisms will provide a theoretical basis for novel therapeutic strategies for disease prevention and treatment. Finally, we discuss therapies targeting the gut microbiota to treat Ang II-related disorders.