Association Between Gut Microbiome Alterations and Hypertension-Related Cardiovascular Outcomes: A Systematic Review and Meta-Analysis

Hypertension (HTN) remains a major modifiable risk factor for cardiovascular disease (CVD), yet the mechanisms linking environmental and metabolic factors to vascular injury are incompletely understood. Recent evidence implicates gut microbiome dysbiosis and microbial metabolites, particularly short-chain fatty acids (SCFAs) and trimethylamine N-oxide (TMAO), in the pathogenesis of hypertension and its cardiovascular complications. We systematically searched PubMed, Embase, Cochrane, Web of Science, and Scopus from inception to 1 October 2025 for observational studies evaluating gut microbiome composition or circulating TMAO levels in adults with hypertension or related cardiovascular outcomes. Random-effects meta-analyses were conducted using standardized mean differences (SMD) for alpha diversity indices and hazard ratios (HR) for TMAO-associated major adverse cardiovascular events (MACE). Heterogeneity (I2), publication bias (Egger’s test), and certainty of evidence (GRADE) were assessed according to PRISMA 2020 guidelines (PROSPERO CRD420251162222). A total of 22 studies (n = 24,512 participants) were included, of which 15 were eligible for quantitative synthesis (11 for alpha diversity, 4 for TMAO). Pooled analysis showed significantly lower microbial diversity among hypertensive versus normotensive individuals (SMD = −0.15, 95% CI −0.25 to −0.05; p = 0.004; I2 = 35%). Circulating TMAO was associated with increased risk of major adverse cardiovascular events (HR = 1.25, 95% CI 1.10 to 1.42; p < 0.001). Funnel plots were symmetric, and Egger’s test indicated no significant bias (p > 0.3). The certainty of evidence was graded as moderate for microbial diversity and high for TMAO-related outcomes. This meta-analysis provides robust evidence that gut microbiome dysbiosis and elevated TMAO levels are associated with hypertension and heightened cardiovascular risk, supporting the concept of a “gut–vascular axis.” Microbiota-targeted interventions such as high-fiber diets, prebiotics, or TMAO-lowering strategies warrant further investigation as adjunctive tools in precision hypertension management.