Controlled Trial Finds Both Caffeinated and Decaffeinated Coffee Alter Gut Microbiome and Produce Modest Mood and Cognitive Changes

Both caffeinated and decaffeinated coffee improved mood and aspects of cognitive performance in a controlled human trial, with effects tied to polyphenols and changes in the gut microbiome, according to a study led by John Cryan at University College Cork in Ireland.

The trial recruited 62 healthy participants, half regular coffee-drinkers and half non-coffee-drinkers. Regular drinkers abstained from coffee for 14 days before entering a 21-day reintroduction phase in which they were randomly assigned to consume either caffeinated or decaffeinated coffee.

Researchers collected blood, saliva, urine and stool samples from participants and assessed their mood, cognition, stress, sleep and behaviour. Consuming caffeinated coffee was associated with lower anxiety and improved attention compared with non-coffee-drinkers. Decaffeinated coffee was linked to improved scores in memory tests and better sleep quality.

Both caffeinated and decaffeinated coffee were associated with lower ratings of stress and depression. Participants’ microbiomes changed rapidly when coffee was removed and then reintroduced. Both regular and decaf coffee were linked to higher levels of beneficial gut bacteria.

Coffee is one of the richest sources of polyphenols which gut microbes convert into biologically active molecules. The analysis suggests that coffee’s effects on cognitive scores correlated with measurements of certain metabolites derived from polyphenols in participants’ urine. “We were surprised by how dynamic the system is,” John Cryan said.

Daniele Del Rio at the University of Parma said a key next step will be to determine how different types of coffee affect the microbiome and that the degree of roasting profoundly influences its chemical composition. Nicola Segata at the University of Trento said the study’s relatively small sample size may limit how broadly the results can be applied.

Telmo Pievani at the University of Padua said the study suggests that the human gut ecosystem may have helped humans adapt relatively rapidly to different diets and environments without requiring genetic change.

1038/s41467-026-71264-8. @NewScientist reported that scientists have long known coffee can influence digestion, cognition and mood thanks partly to interactions with gut microbes. While most prior research focused on caffeine, the new findings underscore the role of polyphenols and their conversion by gut bacteria into biologically active metabolites linked to anti-inflammatory effects.