Caffeine affects several processes in the body, including digestion, stress response, cognition, and gut microbiome. However, the specific mechanisms underlying these effects remain poorly understood.
In a recent study, we explored the influence of coffee on the microbiota–gut–brain axis, an asymmetric reciprocal signaling network between the gut and brain, and whether caffeine was necessary for these consequences in healthy individuals.
They found that regularly drinking caffeinated and decaffeinated coffee can have profound effects on the gut microbiome, which, in turn, regulates mood and stress, according to research published in Nature Communications by APC Microbiome Ireland at University College Cork (UCC).
Among groups, the researchers defined coffee drinkers as having higher levels of certain gut microorganisms, including Cryptobacterium and species in the genus Eggerthella, while possessing lower levels of some metabolites, such as indole-3-propionic acid, indole-3-carboxyaldehyde (compounds), and GABA (neurotransmitter).
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Indole-3-propionic acid is believed to stimulate the secretion of gastric and intestinal acid, while indole-3-carboxyaldehyde may encourage the production of bile acids; both can help clear pathogenic gut bacteria and infections.
Coffee drinkers also had greater levels of Firmicutes bacteria, previously associated with happiness in women.
The study included 31 habitual coffee drinkers and 31 non-drinkers, who were monitored for mood, food, and caffeine intake while providing stool and urine samples to examine gut microbiome composition and stress markers. Subjects who consumed a moderate (3 through 5 cups/day) amount of coffee (defined as the regular consumption of coffee from brewing methods practiced in the United States) were defined as coffee drinkers.
During testing and sample collection, participants abstained from coffee for 2 weeks. At this time, long-term coffee drinkers showed marked changes in their gut flora compared with non-drinkers.
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Coffee was then reintroduced in a blinded way: half received caffeinated coffee, the other half decaffeinated. Both sets of participants experienced lower levels of stress, depression, and impulsivity regardless of whether their drinks contained caffeine, which showed that coffee has a positive effect on mood.
Coffee drinkers were more impulsive and more emotionally reactive, while non-coffee drinkers performed better on memory tests. A subset of these changes in gut metabolites was reversed after cessation, and reintroduction rapidly modified the microbiome independent of caffeine.
Importantly, improvements in what they refer to as learning and memory were observed only in the decaffeinated coffee group, suggesting that something other than caffeine is responsible for these cognitive benefits.
While only caffeinated coffee was linked to decreased anxiety, improved alertness, and attention, similarly, caffeine consumption has been associated with a lower risk of inflammation.
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Corresponding author of the study, Professor John Cryan, Principal Investigator at APC Microbiome Ireland, University College Cork, commented: “Public interest in gut health has risen hugely. The relationship between digestive and mental health is also increasingly being better understood, but the mechanisms behind coffee’s effects on this gut-brain axis have remained unclear.”
“Our findings reveal the microbiome and neurological responses to coffee, as well as their potential long-term benefits for a healthier microbiome. Coffee may modify what microbes do collectively, and what metabolites they use. As the public continues to think about dietary changes for the right digestive balance, coffee has the potential also to be harnessed as a further intervention as part of a healthy, balanced diet.”
“Coffee is more than just caffeine, it’s a complex dietary factor that interacts with our gut microbes, our metabolism, and even our emotional wellbeing,” said Prof. Cryan. “Our findings suggest that coffee, whether caffeinated or decaffeinated, can influence health in distinct but complementary ways.”
Journal Reference:
- Boscaini, S., Bastiaanssen, T.F.S., Moloney, G.M. et al. Habitual coffee intake shapes the gut microbiome and modifies host physiology and cognition. Nat Commun 17, 3439 (2026). DOI: 10.1038/s41467-026-71264-8
