Gut enterotype- and body mass index (BMI)-dependent effects of anthocyanin supplementation on gut microbiota composition in individuals at risk for cognitive decline: a randomized placebo-controlled trial

Anthocyanins, bioactive flavonoids found in berries, modulate gut microbiota composition and influence health outcomes. This study investigated the effects of anthocyanin supplementation on gut microbiota and cognition in older adults (60-80 y) at risk of cognitive decline due to mild cognitive impairment (MCI) or cardiometabolic disorders (CMD). In a 24-week, randomised, double-blind, placebo-controlled trial (<i>n</i> = 99), participants received anthocyanin capsules or placebo. Gut microbiota composition was profiled using 16S rRNA sequencing, considering factors such as baseline enterotype, body mass index (BMI), and age. Overall, alpha diversity remained unchanged, while beta diversity indicated modest but significant intervention effects at the amplicon sequence variants level. Baseline enterotype strongly influenced responsiveness: enterotype one (higher diversity, eubiotic taxa) showed modest but consistent shifts, whereas enterotype two (dysbiotic, Bact2-like) exhibited broader but less coherent changes. BMI-specific responses included enrichment of <i>Oscillibacter</i> and <i>Ezakiella</i> in healthy-weight individuals and Bacteroidota taxa in obese participants, alongside consistent reductions in Firmicutes. Age stratification revealed heterogeneous, quartile-specific taxa modulations. Cognitive performance, measured by episodic memory, was unaffected, and microbial shifts did not mediate intervention effects. These findings demonstrate that anthocyanins selectively modulate the gut microbiome in an age-, BMI-, and enterotype-dependent manner, underscoring the importance of personalized microbiome-informed nutritional interventions.