Gut bacteria linked to key brain chemicals in first-of-its-kind human study

In a study published in Molecular Psychiatry, the research team found that microbial pathways involved in producing and breaking down neuroactive compounds were associated with levels of GABA and glutamate in specific regions of the human brain. 

GABA and glutamate are two of the brain’s most important chemical messengers. GABA predominantly dampens neural activity, while glutamate promotes excitation. The balance between them, known as excitatory/inhibitory (or E/I balance), plays an important role in neuroplasticity (the brain’s ability to change, grow, and reorganise itself by forming new neural connections), cognition and mental health. 

Much of the evidence linking the gut microbiome with these brain systems has until now come from animal and preclinical research. 

The team investigated 61 healthy young women aged 17–25. Researchers used proton magnetic resonance spectroscopy (a non-invasive brain-imaging technique) to measure GABA and glutamate in three brain regions. Stool samples were also analysed using shotgun metagenomic sequencing to identify the genetic capacity of participants’ gut microbes to carry out metabolic processes involving GABA, glutamate, short-chain fatty acids and other neuroactive compounds. 

The researchers found that the relationship between the gut microbiome and brain chemistry was not uniform across the brain. Instead, different microbial pathways were associated with GABA, glutamate and E/I balance in different brain regions. 

Surprisingly, the inferior occipital gyrus (a visual-processing region included in the study as a comparison area) showed the broadest range of associations with microbial pathways. These included pathways involved in glutamate degradation, GABA metabolism, short-chain fatty acids, inositol and p-cresol. 

The anterior cingulate cortex (a region involved in attention, cognitive control and emotional regulation) showed a distinct pattern involving microbial glutamate and propionate pathways. The dorsolateral prefrontal cortex, which is involved in cognitive control and emotion regulation, showed a more selective association involving a microbial GABA-production pathway. 

The research team also explored whether the same microbial pathways were related to psychological wellbeing. 

They found associations between specific gut microbial pathways and self-reported anxiety, depressive symptoms and sleep quality. A GABA-related microbial pathway was associated with trait and social anxiety, while pathways involved in tryptophan metabolism were associated with depressive symptoms and social anxiety. A pathway involved in producing the short-chain fatty acid propionate was also associated with poorer sleep quality. 

The researchers stress that the findings show associations rather than cause and effect. The study was cross-sectional, meaning the researchers cannot determine whether differences in the gut microbiome influence brain chemistry, whether brain and behavioural factors influence the gut, or whether other biological processes affect both. 

The study also measured the genetic potential of the gut microbiome to perform particular metabolic functions rather than directly measuring the metabolites produced by the bacteria. 

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Notes to editors 

• Professor Kathrin Cohen Kadosh is available for interview; please contact mediarelations@surrey.ac.uk to arrange. 
• The study was conducted by researchers at the University of Surrey and the University of Roehampton. 
• Funding for the study was provided by FrieslandCampina. 
• The full paper is available at: https://doi.org/10.1038/s41380-026-03813-y