Effects of Gut Microbiota-Modulating Interventions on Systemic Inflammation and Functional Outcomes in Established Cardiovascular Disease: A Systematic Review

Cardiovascular disease remains a leading cause of morbidity and mortality worldwide, with persistent residual inflammatory risk despite advances in contemporary pharmacotherapy. Growing evidence implicates the gut-heart axis in the pathogenesis of atherosclerosis, heart failure, and cerebrovascular disease through mechanisms involving dysbiosis, intestinal permeability, endotoxemia, and systemic inflammation. This systematic review aimed to evaluate the effects of gut microbiota-modulating interventions on systemic inflammatory markers and functional or clinical outcomes in adults with established cardiovascular disease. A comprehensive search of PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE), Scopus, and Web of Science was conducted for randomized controlled trials published between January 2020 and December 2024. Eligible studies included adult patients with documented coronary artery disease, heart failure, or cerebrovascular accident receiving probiotics, postbiotics, or microbiota-targeted antibiotics compared with a placebo or standard care. Four randomized clinical trials met the inclusion criteria. Across studies, microbiota-modulating interventions were associated with significant reductions in inflammatory biomarkers, including interleukin-1β, high-sensitivity C-reactive protein, and lipopolysaccharide, suggesting attenuation of metabolic endotoxemia and systemic inflammatory activity. Improvements in functional capacity were observed in one chronic heart failure trial, whereas a multicenter heart failure study did not demonstrate significant changes in ventricular function or inflammatory markers. Overall, the available evidence indicates that microbiota-targeted interventions may exert anti-inflammatory effects in established cardiovascular disease; however, consistent functional or structural cardiac benefits have not been demonstrated. The current literature is limited by small sample sizes, heterogeneous interventions, and short follow-up durations. Larger, adequately powered trials with standardized endpoints are needed to determine whether modulation of the gut microbiota can translate into meaningful clinical benefit in secondary cardiovascular prevention.