Abstract
Hypertension (HTN), a multifactorial condition and major modifiable risk factor for cardiovascular disease, has been increasingly linked to gut microbiota (GM) alterations, encouraging investigation into its potential role in the progression of hypertension-mediated organ damage (HMOD). This systematic review aims to evaluate the role of GM in HTN pathophysiology and its contribution to HMOD, with the aim of identifying potential microbiota-related targets for personalized therapeutic strategies. The study, registered in PROSPERO and conducted according to PRISMA guidelines, involved a comprehensive search of five databases up to January 2025, selecting human and complementary animal studies investigating the relationship between GM, HTN, and HMOD. While few studies directly assessed HMOD, emerging evidence suggests a protective role of GM and its metabolites against cardiovascular, cerebral and renal injury. Heterogeneity in design, small sample sizes and a lack of standardized methodologies limited comparability therefore we did not perform a meta-analysis. In conclusion, GM dysbiosis and its metabolites are increasingly recognized as key providers to HMOD, offering encouraging targets for future preventive and therapeutic strategies. A substantial proportion of the available evidence originates from preclinical animal studies. While these findings provide valuable mechanistic insights, further longitudinal and interventional research in human populations is warranted to confirm their translational relevance.