A new study published in Nature Communications reveals that habitual coffee consumption produces distinct and measurable changes in the gut microbiome, gut metabolites, and cognitive and emotional behavior in healthy adults. Crucially, many of these effects appear to be driven by components of coffee beyond caffeine alone, suggesting that the relationship between coffee and the brain runs deeper than its stimulant properties.

Study Overview

Researchers from University College Cork and the University of Parma recruited 62 healthy adults aged 30 to 50, comparing 31 habitual coffee drinkers (3 to 5 cups per day) with 31 non-coffee drinkers. Using shotgun metagenomics (a comprehensive method for analyzing the genetic material of all microorganisms in a sample) alongside targeted and untargeted metabolomics, the team profiled participants' gut microbiota, gut and urinary metabolites, cognitive performance, mood, immune markers, and stress responses at multiple time points.

The study then went further. Coffee drinkers abstained from all coffee for two weeks, after which they were randomized into two groups: one reintroducing caffeinated coffee, the other decaffeinated, for a further three weeks. This design allowed researchers to separate the effects of caffeine specifically from those of coffee's broader chemical profile, including its polyphenols, diterpenes, and melanoidins.

Key Findings

Gut microbiome

• Coffee drinkers showed increased levels of Cryptobacterium curtum and Eggerthella species in their gut compared to non-drinkers.
• During the abstinence period, Cryptobacterium curtum levels declined across three consecutive timepoints, indicating a direct, ongoing influence of coffee on this species.
• When coffee was reintroduced (whether caffeinated or decaffeinated) all seven microbial species that differed between coffee drinkers and non-drinkers showed significant shifts, suggesting sensitivity to coffee's non-caffeine compounds.
• Overall gut microbial diversity was different between coffee drinkers and non-drinkers, but was not significantly changed by the withdrawal or reintroduction phases, suggesting coffee affects specific bacterial strains rather than the microbiome broadly.

Metabolites

• Coffee drinkers had lower gut levels of two gut-derived indole metabolites (indole-3-propionic acid (IPA) and indole-3-carboxyaldehyde (ICA)) and the neurotransmitter GABA, all of which have roles in gut barrier integrity, neuroprotection, and anxiety regulation.
• During abstinence, ICA levels rose significantly, suggesting this metabolite is particularly sensitive to the presence or absence of coffee.
• Decaffeinated coffee reintroduction restored polyphenol-derived metabolites to levels matching habitual drinkers, while caffeine metabolites only returned with caffeinated coffee, confirming two distinct metabolic pathways at work.

Cognition and behavior

• Coffee drinkers scored higher on measures of impulsivity and emotional reactivity compared to non-drinkers.
• After two weeks of abstinence, both impulsivity and emotional reactivity scores dropped significantly.
• Reintroduction of caffeinated coffee reduced anxiety and psychological distress; decaffeinated coffee improved sleep quality, physical activity levels, and episodic memory performance.
• Both types of coffee reduced perceived stress, depression symptoms, and impulsivity following reintroduction.

Immune and stress markers

• Coffee drinkers had lower baseline levels of CRP (a marker of systemic inflammation) and higher levels of the anti-inflammatory cytokine IL-10.
• When coffee was withdrawn, CRP and TNFα levels rose, suggesting a protective, anti-inflammatory role for habitual coffee consumption.
• Cortisol levels and stress reactivity were similar between coffee drinkers and non-drinkers throughout the study, indicating that coffee's mood effects occur independently of the stress hormone system.

Why It Matters

The gut-brain axis (the bidirectional communication pathway between the gut microbiome and the brain) is increasingly understood to shape mood, cognition, and behavior. This study provides some of the first prospective, controlled human evidence that a widely consumed beverage directly and measurably influences this system.

The finding that decaffeinated coffee produces meaningful effects on the microbiome, metabolites, mood, and cognition challenges the common assumption that coffee's health effects are primarily caffeine-driven. Coffee contains hundreds of bioactive compounds including chlorogenic acids, melanoidins, and other polyphenols many of which reach the colon largely intact and interact with gut bacteria. The study's integrated analysis identified nine key metabolites (including theophylline, caffeine, and phenolic acids) that were strongly linked to specific microbial species and to cognitive and behavioral outcomes, tracing a clear molecular pathway from cup to brain.

The observation that non-coffee drinkers showed lower impulsivity, better cognitive stability, and more favorable gut metabolite profiles raises questions about the net cognitive tradeoffs of habitual coffee consumption, and underscores that the picture is more nuanced than a simple benefit or harm.

Takeaways

• Habitual coffee consumption reshapes the gut microbiome in species-specific ways, with effects that appear within days of starting or stopping coffee and that operate largely independently of caffeine.
• Coffee drinkers show higher impulsivity and emotional reactivity than non-drinkers, both of which decline during abstinence, a finding worth considering for those managing anxiety or mood instability.
• Caffeinated coffee appears to reduce anxiety and sharpen attention; decaffeinated coffee shows benefits for memory, sleep, and physical activity, suggesting that coffee type may be worth tailoring to individual health goals.
• Reduced gut levels of IPA and GABA in coffee drinkers may have implications for gut barrier health and anxiety regulation, and warrant further investigation.
• The study's relatively small sample (62 participants), short intervention period, and predominantly white Irish cohort are important limitations; results should be interpreted cautiously and replicated in more diverse populations.

Read the research: Boscaini et al., Nature Communications (2026). Habitual coffee intake shapes the gut microbiome and modifies host physiology and cognition. https://doi.org/10.1038/s41467-026-71264-8