Background: 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. Objectives: 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. Methods: 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. Results: Fifty RCTs (n = 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; I2 = 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 Bifidobacterium (81.8%), Akkermansia muciniphila (50%), and Faecalibacterium prausnitzii (45.5%), and with decreases in potentially pathogenic taxa such as Enterobacteriaceae and Clostridium 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. Conclusions: 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.
Alshatari et al. (Sat,) studied this question.