Mesenchymal stem cell therapy modulates gut microbial diversity and short-chain fatty acid pathways in preclinical models: a systematic review with implications for hypertension

Background: Mesenchymal stem cells (MSCs) possess regenerative, immunomodulatory, and anti-inflammatory properties. Emerging evidence indicates that part of their therapeutic effects may be mediated through modulation of the gut microbiota, which plays a key role in cardiovascular health and hypertension via the gut–vascular axis. However, the specific contribution of MSC-induced microbial changes to hypertension remains unclear. This systematic review summarizes current evidence on MSC-mediated modulation of gut microbiota and highlights opportunities for translational research in hypertension.
Methods: A systematic search was performed according to PRISMA 2020 guidelines across PubMed, Scopus, Ovid MEDLINE, EBSCO, and Web of Science for in vivo studies published in English between 2018 and 2025. Eligible studies investigated the effects of MSC therapy on gut microbial composition and diversity.
Results: Of 1,190 records screened, 31 preclinical studies met the inclusion criteria. MSC therapy consistently enhanced gut microbial diversity, normalized the Firmicutes-to-Bacteroidetes ratio, enriched short-chain fatty acid (SCFA)-producing genera such as Akkermansia, Roseburia, Blautia, and Faecalibaculum, and reduced pro-inflammatory taxa including Escherichia-Shigella and Desulfovibrio. These microbial shifts were associated with improved gut barrier integrity, reduced endotoxemia, and decreased systemic inflammation. Only one study directly examined hypertension, underscoring a major evidence gap.
Conclusion: MSC therapy promotes gut microbial balance and SCFA-related pathways that support vascular and immune homeostasis. These findings provide a mechanistic framework for microbiota-mediated blood pressure regulation and warrant targeted studies using validated hypertensive models to establish MSCs as a potential microbiota-based therapy for hypertension.