Regular Coffee Drinking Can Shape the Gut Microbiome—And Your Mood

"Don't talk to me until I've had my coffee" is a common refrain heard in offices around the world; but is there a grain of truth behind this saying? Can regularly drinking coffee affect your mood?

In a new study published in Nature Communications, researchers found that drinking either caffeinated or decaffeinated coffee can influence the microbiota–gut–brain axis and induce noticeable differences in mood, stress perception, and cognitive performance.

"For decades we've thought of coffee primarily as a stimulant," principal investigator Prof. John Cryan, professor and chair of the Department of Anatomy and Neuroscience at University College Cork, told Technology Networks. "Our work suggests it's also a powerful dietary signal for the gut microbiome, and that may be one reason it has such widespread effects throughout the body and brain."

Coffee and the gut microbiome

Recent studies have shown that coffee drinking can impact the gastrointestinal tract; coffee can increase stomach acidity and encourage the release of cholecystokinin, a hormone that stimulates gallbladder function and aids in digestion. Coffee's effects on the brain are also becoming better understood; functional brain imaging studies have found differences in brain connectivity between habitual coffee drinkers and non-drinkers. Now, researchers are focused on a combination of these factors, studying how coffee's impacts on the gut might also influence what is going on in the brain.

"Coffee is one of the most widely consumed beverages in the world and one of the richest sources of dietary polyphenols, naturally occurring plant compounds that are metabolized by the gut microbiome," explained Cryan. "While coffee has been linked to numerous health benefits, most research has focused on caffeine. We wanted to understand how coffee as a whole influences the microbiome, metabolism, immunity and, ultimately, behavior and cognition."

In the new study, researchers compared a group of 31 non-coffee drinkers (NCDs) against 31 regular coffee drinkers (CDs), evaluating their food intake, cravings, cognitive function, gastrointestinal function, and answers to various physical and mental wellbeing questionnaires. Stool samples were also assessed using targeted and untargeted metabolomics approaches to identify any changes in fecal microbiome composition.

The researchers found that Cryptobacterium curtum, Eggerthella sp. CAG:209, Eggerthella sp. Cag 51_9, and Firmicutes CAG:94 species were significantly decreased in the fecal samples of NCDs compared with CDs at baseline. In contrast, Velonella parvula, Velonella sp. ACP1 and Haemophilus parainfluenzae were increased in NCD participants.

"[Eggerthella sp and Cryptobacterium curtum] are fascinating organisms because relatively little is known about their biology," explained Cryan. "Eggerthella species are recognized for their ability to metabolize a wide range of dietary compounds, including plant polyphenols, and they may also influence bile acid metabolism and other host metabolic pathways. Cryptobacterium curtum is more commonly associated with the oral microbiome, making its enrichment in coffee drinkers particularly intriguing."

"Rather than focusing on individual bacteria, I think the more important message is that coffee appears to reshape microbial communities and, importantly, the metabolites they produce. Those metabolites are likely to be the key mediators linking diet, the microbiome, and the brain."

Re-introducing coffee boosts mood, even when decaf

After taking these baseline measurements and comparisons, the CDs in the study each abstained from drinking coffee for a two-week washout period. After this, the CDs were randomly split into two groups and asked to drink either only caffeinated or decaffeinated coffee for 20 days.

After reintroducing coffee, both the caffeinated and decaffeinated groups reported decreases in perceived stress, impulsivity, and self-reported symptoms of depression.

"This was one of the biggest surprises of the study. It suggests that caffeine is only part of the story," Cryan said.

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"Coffee contains hundreds of biologically active compounds, including polyphenols, fibers, and melanoidins, many of which interact with the gut microbiome. The fact that decaffeinated coffee produced many of the same effects on perceived stress, depressive symptoms, and inflammatory markers suggests these other components contribute substantially to coffee's biological effects, probably through microbiome-mediated pathways."

However, the presence of caffeine did produce some unique effects. Only the reintroduction of caffeinated coffee resulted in reductions in anxiety and psychological distress, as well as improvements in blood pressure and attention. In the same manner, only decaffeinated coffee was associated with enhancements in sleep, physical activity, and some memory domains.

"Caffeine has well-established effects on the brain through blockade of adenosine receptors, so it was not surprising that caffeinated coffee had stronger effects on attention and anxiety," Cryan explained. "The improvements in memory observed with decaffeinated coffee suggest that non-caffeine components may influence cognition through different mechanisms, perhaps involving sleep quality, immune signaling or the gut microbiome. Rather than viewing caffeinated and decaffeinated coffee as competing, I think our findings suggest they may have complementary biological effects."

Could the gut microbiome explain how an individual reacts to coffee?

While this study does suggest that coffee plays a role as a modulator of the microbiota–gut–brain axis, the researchers do acknowledge some limitations on this work.

"This was a carefully controlled intervention study, but it was relatively modest in size and involved healthy adults, so larger studies in more diverse populations will be important," noted Cryan. "Although we identified strong links between changes in the microbiome, metabolites and behavior, we cannot conclude that the microbiome directly caused the behavioral changes. Individual responses to coffee are also likely to vary according to genetics, habitual diet, sleep patterns, and baseline microbiome composition."

Understanding what affects an individual's response to the effects of coffee is one of the topics that Cryan and his colleagues are most interested in exploring, he said.

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"One of the most exciting questions is why individuals respond differently to coffee. We suspect that variation in the gut microbiome explains at least some of this diversity and could eventually help us personalize dietary recommendations," said Cryan.

Speaking on potential future research, Cryan said: "More broadly, we want to understand which specific coffee compounds are responsible for these effects and whether they contribute to the well-established associations between moderate coffee consumption and healthy aging, including lower risks of Parkinson's disease and dementia."

"Ultimately, our goal is to better understand how everyday dietary choices shape brain health through interactions with the gut microbiome."

Reference: Boscaini S, Bastiaanssen TFS, Moloney GM, et al. Habitual coffee intake shapes the gut microbiome and modifies host physiology and cognition. Nat Commun. 2026;17(1):3439. doi: 10.1038/s41467-026-71264-8 

About the interviewee:

Dr. John F. Cryan is professor and chair of the Department of Anatomy and Neuroscience at University College Cork (UCC), where he has served as vice president for research and innovation since 2021. He is also a principal investigator at APC Microbiome Ireland. He received a BSc in biochemistry and a PhD in pharmacology from the University of Galway and undertook a visiting fellowship at the University of Melbourne. This was followed by postdoctoral training at the University of Pennsylvania and The Scripps Research Institute. Before joining UCC in 2005, he spent four years as a group leader at Novartis in Basel.

Over the past two decades, Cryan's research has helped transform understanding of the microbiota–gut–brain axis, revealing how interactions between the gut microbiome and the brain influence stress resilience, behavior, neurodevelopment, aging, and psychiatric and immune-related disorders across the lifespan. Cryan is senior editor of Neurobiology of Stress and serves on the editorial boards of numerous international journals. He has co-edited four books and is co-author of the international bestselling The Psychobiotic Revolution: Mood, Food, and the New Science of the Gut–Brain Connection (National Geographic Press).

His contributions have been recognized through numerous international honors, including election to the Royal Irish Academy in 2017, the Datta Lectureship Award from FASEB in 2022, and election to the European Academy of Microbiology in 2026. He has delivered TEDMED and TEDx talks, and his work has been featured widely in international media, including the Netflix documentary Hack Your Health: The Secrets of the Gut.