Clinical Evidence Linking the Gut Microbiome and Functional Dyspepsia: A Systematic Review and Meta-Analysis

Background/Objectives: Accumulating evidence and clinical observations suggest that the gut microbiome plays a crucial role in functional dyspepsia (FD). However, the precise characterization of this relationship is unclear. This systematic review and meta-analysis aimed to elucidate the potential role of the gut microbiome in FD based on evidence from published clinical studies. Methods: A comprehensive search of three databases (PubMed, Google Scholar, and Web of Science) was conducted, and 17 relevant clinical studies, including 8 observational studies and 9 interventional studies, published up to September 2025, were identified. Data on the gut microbiome and FD were extracted and subjected to meta-analysis. Results: Meta-analysis revealed no significant differences in gut microbiota α- or β-diversity between patients with FD and healthy controls (Shannon index: standardized mean difference [SMD] = -0.12, 95% confidence interval [CI] -0.90 to 0.67, I² = 88%). In contrast, effective interventions induced notable shifts in the microbial community structure (pooled SMD = 0.27, 95% CI -0.28 to -0.83, I² = 58%). These shifts were accompanied by increased short-chain fatty acid (SCFA) production and intestinal tight-junction protein levels, which coincided with improved FD symptoms. Conclusions: Although no significant differences in the gut microbiota were detected between patients with FD and healthy controls, interventions in patients with FD induced marked changes in the microbial community. Modulation of gut microbiota-related metabolites, such as SCFAs, may represent a promising therapeutic strategy for the management of FD.