Effects of Polyphenol Supplementation on Gut Microbiota Composition and Fecal Short-Chain Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

<b>Background:</b> Polyphenols interact bidirectionally with the gut microbiota and may influence short-chain fatty acid (SCFA) production, yet evidence from human randomized controlled trials (RCTs) has not been comprehensively synthesized. <b>Objectives:</b> In this systematic review and meta-analysis, we evaluated the effects of polyphenol supplementation on gut microbiota composition, microbial diversity, and fecal SCFA concentrations in adults and examined moderators of these associations. <b>Methods:</b> Five databases were searched through October 2023 for RCTs assessing oral polyphenol supplementation in adults. Eligible studies reported outcomes related to gut microbiota composition or fecal SCFAs. Random-effects meta-analyses were conducted for SCFA outcomes, and subgroup analyses examined effects by polyphenol class, dose, duration, health status, and analytical methods. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence using GRADE. <b>Results:</b> Fifty RCTs (<i>n</i> = 2042 participants) were included. Polyphenol supplementation was associated with an increase in total SCFAs in 70.6% of studies and with significantly higher butyrate concentrations (pooled SMD = 0.48; 95% CI: 0.32-0.64; <i>I</i>² = 58%). Acetate and propionate increased in 75% and 71.4% of studies, respectively. A shift toward a more butyrogenic fermentation profile was observed. Polyphenol supplementation was associated with increases in the relative abundance of beneficial genera, including <i>Bifidobacterium</i> (81.8%), <i>Akkermansia muciniphila</i> (50%), and <i>Faecalibacterium prausnitzii</i> (45.5%), and with decreases in potentially pathogenic taxa such as <i>Enterobacteriaceae</i> and <i>Clostridium</i> spp. Increases in alpha diversity were reported in 66.7% of studies, and increases in beta diversity were reported in 87.5%. Associations tended to be stronger in individuals with metabolic disorders and in interventions lasting ≥12 weeks. <b>Conclusions:</b> Polyphenol supplementation is associated with favorable shifts in gut microbiota composition, higher fecal SCFA concentrations-particularly butyrate-and modest changes in microbial diversity. These findings should be interpreted as associations rather than evidence of mechanistic or prebiotic effects. Further mechanistic, dose-controlled, and long-term human studies are needed to determine whether these microbiota-related changes translate into clinically meaningful outcomes.