The study funded by the Institute for Scientific Information on Coffee (ISIC) examined how coffee affects cognition, mood, behavior, immunity, and the gut microbiome in healthy adults by comparing regular coffee drinkers with non-drinkers and tracking changes during abstinence and reintroduction of caffeinated or decaffeinated coffee.
“The study’s comprehensive insights pave the way for future investigations harnessing these interactions for potential health interventions and underscore the importance of understanding coffee’s multifaceted effects on human physiology,” the researchers wrote in Nature Communications.
How coffee supports brain function and gut health
Coffee composition varies with how producers grow, process, roast, and brew it, however, most coffee will contain bioactive compounds such as caffeine, polyphenols, diterpenes, and melanoidins.
Research has linked moderate coffee consumption to lower risks of type 2 diabetes, cardiovascular disease, liver disease, cancer, depression and neurodegenerative conditions like Parkinson’s and Alzheimer’s. It directly affects the brain by altering neural activity and functional connectivity, particularly in areas related to emotion and cognition.
It can also influence health through indirect pathways, especially via the gut microbiome. Its fiber-like compounds and polyphenols act like prebiotics, supporting beneficial gut bacteria and increasing production of short-chain fatty acids.
Coffee consumption correlates strongly with changes in gut microbiome composition, including increases in beneficial species, which the researchers of the new study noted may in turn affect brain function through the microbiota–gut–brain axis.
Coffee influences neurocognition, immunity and gut composition
The researchers recruited 62 healthy adults in Ireland, split evenly between non-coffee drinkers and moderate coffee drinkers. They compared both groups at baseline, then asked coffee drinkers to stop consuming coffee for two weeks. After this washout period, they randomly assigned them to consume either caffeinated or decaffeinated coffee for three weeks under controlled conditions.
Participants attended multiple study visits where researchers collected biological samples (stool, blood, saliva, urine), recorded diet and caffeine intake, and assessed mood, cognition, stress, and behaviour using questionnaires and cognitive tests. They also exposed participants to a standardized stress test to measure physiological and psychological stress responses.
Researchers analyzed samples to measure cortisol, inflammatory markers, metabolites, and gut microbiome composition using advanced sequencing and metabolomics techniques. They also examined genetic differences related to caffeine sensitivity.
“Through cutting-edge methodologies, this study unearthed distinctive effects of coffee on emotional reactivity, immune responses, and microbial composition, showcasing its potential as a modulator of the microbiota-gut-brain axis,” said the researchers.
Results suggested that coffee drinkers exhibited higher impulsivity and emotional reactivity than non-drinkers. During abstinence, attention improved while impulsivity and emotional reactivity decreased, and reintroducing both caffeinated and decaffeinated coffee reduced perceived stress, depressive symptoms, and impulsivity, whereas only caffeinated coffee reduced anxiety and psychological distress.
Cortisol levels remained similar across groups, suggesting coffee did not significantly alter physiological stress responses. However, the researchers noted that habitual consumption may attenuate cortisol responsiveness over time.
Coffee consumption was associated with reduced inflammation, characterised by lower CRP and IL-6 levels and higher IL-10. These effects reversed during abstinence and partially returned following reintroduction, which the researchers suggested showed a modulatory effect of coffee, particularly caffeine, on immune function.
Metabolomic analyses found that coffee altered multiple metabolites, including neuroactive compounds such as gamma-aminobutyric acid (GABA) and indole-3-propionic acid (IPA), although the researchers noted the functional implications of these changes remain unclear. However, they did indicate that coffee influences signalling along the gut–brain axis.
Furthermore, coffee affected gut microbiome composition, increasing the abundance of specific taxa such as Eggerthella and Cryptobacterium and altering microbial diversity. The changes disappeared during abstinence and reappeared after reintroduction, and similar effects were observed with decaffeinated coffee, which the researchers said indicated that non-caffeine components contributed to these changes.
Finally, dietary polyphenol intake increased following both caffeinated and decaffeinated intake, but individual responses varied depending on genetics and microbiome composition.
“Coffee influenced the gut microbiome, increased beneficial (poly)phenols and metabolites, and provided anti-inflammatory effects, suggesting that coffee, regardless of caffeine content, supports cognitive, psychological, immune, and metabolic health in distinct but complementary ways,” the researchers concluded.
“These findings not only illustrate the immediate microbial and neurotransmitter responses to caffeine but also emphasise the long-term implications for metabolite production within the microbiome.”
They added that future studies investigating the impact of coffee on the gut microbiome should incorporate direct measures of stool transit time.
Journal: Nature Communications; doi: 10.1038/s41467-026-71264-8; “Habitual coffee intake shapes the gut microbiome and modifies host physiology and cognition.” Authors: Boscaini, S. et al.
