Impact of Low‐Dose Cranberry Polyphenols on Gut Microbiota and Circulating Polyphenol Metabolites in Overweight and Obese Individuals (A Randomized Double‐Blind Placebo‐Controlled Clinical Pilot Study)

ABSTRACT Cranberry polyphenols reach the colon largely unmetabolized, where they interact with the gut microbiota to generate bioactive metabolites. However, few human studies have examined both the microbial and systemic metabolic responses to cranberry polyphenol intake, particularly in populations with metabolic risk. In this randomized, double‐blind, placebo‐controlled pilot study, 45 overweight or obese adults received either cranberry juice providing 54.5 mg/day of total polyphenols or a placebo for 6 weeks. Serum and urinary polyphenol metabolites were quantified via UPLC–MS/MS, and gut microbiota composition was assessed by 16S rRNA gene sequencing. Cranberry consumption significantly increased serum and urinary concentrations of catechol‐O‐sulfate and 4‐hydroxyhippuric acid, indicating enhanced polyphenol absorption and metabolism. While no overall shift was observed in gut microbial alpha diversity, subgroup analyses revealed increased richness in obese participants and females. Cranberry consumption was associated with taxonomic shifts, including increased abundance of Anaerostipes , Eubacterium hallii group, and Eggerthella . Notably, Eggerthella was not detected at baseline but was detected after 6 weeks of cranberry consumption in 8 of 25 participants. Sparse partial least squares analysis showed a positive association between Eggerthella and serum 3‐(3‐hydroxyphenyl)propionic acid. These findings suggest a possible microbe–metabolite relationship associated with cranberry intake, although the observed associations are correlative and require further functional validation.