Habitual coffee intake shapes the microbiome, modifies physiology and cognition

Abstract

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.

Introduction

Coffee is a plant-based beverage made from processed coffee beans. Its flavour and composition vary based on the bean type, ripeness, processing, roasting, and brewing methods. Key phytochemicals in coffee include alkaloids (like caffeine), (poly)phenols (such as phenolic acids), diterpenes, and melanoidins formed during roasting. Moderate coffee consumption is associated with various health benefits, including reduced risks of type 2 diabetes, liver disease, cardiovascular diseases, and cancer. In a large cross-sectional study of 468,629 individuals without clinical cardiovascular disease, light-to-moderate coffee consumption was linked to lower rates of all-cause mortality, cardiovascular mortality, and stroke incidence. Furthermore, coffee intake is consistently associated with a reduced risk of Parkinson’s disease in a dose-dependent manner, across multiple human cohorts. Meta-analyses have also found that coffee consumers face a lower risk of depression, and one meta-analysis of cohort studies examining cognitive decline, showed that coffee consumption accounted for a 27% reduction in the incidence of Alzheimer’s disease.

These systemic benefits are paralleled by evidence that coffee impacts the brain directly, shaping both neural activity and cognitive outcomes. Functional MRI studies show that habitual coffee drinkers exhibit altered functional connectivity in regions linked to sensory, motor, and emotional processing. These changes appear to depend on frequency of intake, suggesting that regular coffee consumption may influence brain function and emotional regulation. Recent data show a positive correlation between cognitive performance, particularly memory and processing speed, in older adults. Coffee consumption causes a temporary rise in cortisol levels, followed by normalization with habitual use, indicating physiological adaptation. However, the effects of coffee on stress remain inconclusive, with studies showing mixed results.

Coffee also affects the gastrointestinal tract. It increases stomach acidity and stimulates the release of hormones that aid digestion. Both caffeinated and decaffeinated coffee promote the contractility of ileal and colonic smooth muscle, helping prevent constipation. It is becoming clear that coffee influences human health and physiology through both direct and indirect mechanisms. Direct effects arise from interactions between coffee compounds or their circulating metabolites and specific biological targets, while indirect effects involve changes to systems such as possibly via the gut microbiome.