Coffee influences multiple physiological processes, including gut function, stress, cognition, and the microbiome. However, the mechanisms underlying these effects remain poorly understood. In this study, we examined coffee’s impact on the microbiota–gut–brain axis—a bidirectional communication pathway between the gut microbiome and the brain—and assessed whether these effects occur independently of caffeine in healthy participants. Our primary outcome was microbiota composition and function, whereas the secondary outcome was gut microbial metabolites and coffee-related metabolites (NCT05927038 and NCT05927103). Significant group differences emerged in faecal microbiome composition, with coffee drinkers showing increased relative abundance of Cryptobacterium and Eggerthella species, alongside reduced levels of the metabolite’s indole-3-propionic acid, indole-3-carboxyaldehyde, and the neurotransmitter γ-aminobutyric acid. Behaviourally, coffee drinkers exhibited greater impulsivity and emotional reactivity, whereas non-coffee drinkers demonstrated better memory performance. Some alterations in the faecal metabolome were reversible following coffee abstinence, and reintroduction triggered acute microbiome changes independent of caffeine. An integrated model identified nine key metabolites—including theophylline, caffeine, and selected phenolic acids—strongly linked to microbial species and cognitive measures. These findings reveal previously unrecognised effects of coffee on the microbiota–gut–brain axis, suggesting that microbiome profiles could potentially predict coffee consumption patterns and highlighting a close association between coffee intake and gut microbial composition. Here, the authors investigate coffee’s impact on the microbiota–gut–brain axis and assess whether these effects occur independently of caffeine in healthy participants from two clinical trials.
Boscaini et al. (2026) studied this question.