Mesenchymal stem cell therapy and gut microbiota modulation in preclinical disease models: a systematic review with implications for hypertension.

Mesenchymal stem/stromal cells (MSCs) have regenerative and immunomodulatory properties and may influence gut microbial responses. This systematic review synthesised preclinical evidence on MSC-associated gut-microbiota modulation and considered its implications for hypertension. PubMed, Scopus, Ovid MEDLINE, EBSCOhost Academic Search Elite and Web of Science were systematically searched. Eligible in vivo studies were synthesised according to PRISMA 2020, and risk of bias was assessed using the SYRCLE tool. Thirty-one studies were included. Among 27 studies reporting α-diversity, 11 described an increase, three a decrease, 11 no significant difference and two a change without a clear direction. Twenty-seven studies reported β-diversity outcomes, with heterogeneous evidence of between-group differences in community composition. Four studies assessed the Firmicutes-to-Bacteroidetes ratio: three reported a lower ratio and one a higher ratio after intervention. Three studies directly quantified short-chain fatty acids, five used direct metabolomics or targeted bile-acid profiling, 18 assessed gut-barrier outcomes and 27 assessed inflammatory or immune outcomes. Of 310 risk-of-bias judgements, 74.5% were unclear and 25.5% were low risk. Only one study used a pulmonary-hypertension model; none directly evaluated systemic hypertension. The findings indicate context-dependent microbial, metabolic, barrier and immune responses rather than a universal restoration pattern. Concurrent microbiota and host changes did not generally demonstrate causal mediation, and enrichment of taxa associated with short-chain fatty-acid production could not substitute for direct metabolite measurement. MSC-associated gut-microbiota modulation is biologically plausible and warrants targeted mechanistic investigation. However, the current preclinical evidence does not establish an antihypertensive effect, particularly in systemic hypertension.