A study published in Molecular Psychiatry has found that the neuroactive potential of gut bacteria is associated with levels of GABA and glutamate in specific regions of the human brain, providing the first direct evidence in living humans of a relationship between gut microbial function and brain neurochemistry. Teams at the University of Surrey and the University of Roehampton conducted the research.
GABA and glutamate are the brain’s primary inhibitory and excitatory neurotransmitters, respectively. The balance between them, known as excitatory/inhibitory balance, plays a central role in neuroplasticity, cognition, and mental health. Until now, most evidence linking the gut microbiome to these systems has come from animal and preclinical studies
The study investigated 61 healthy young women aged 17 to 25. Proton magnetic resonance spectroscopy was used to measure GABA and glutamate concentrations in three brain regions: the anterior cingulate cortex, the dorsolateral prefrontal cortex, and the inferior occipital gyrus. Stool samples were analysed using shotgun metagenomic sequencing to assess the genetic capacity of participants’ gut microbiota to perform metabolic processes involving GABA, glutamate, short-chain fatty acids, and other neuroactive compounds.
The findings showed that associations between microbial pathways and brain chemistry were regionally specific rather than uniform. The inferior occipital gyrus showed the broadest range of microbial associations, while the anterior cingulate cortex showed links to glutamate and propionate pathways, and the dorsolateral prefrontal cortex showed a more selective association with a GABA-production pathway.
The researchers also found associations between specific microbial pathways and self-reported anxiety, depressive symptoms, and sleep quality. A GABA-related pathway was associated with trait and social anxiety, tryptophan metabolism pathways were linked to depressive symptoms, and a propionate-producing pathway was associated with poorer sleep.
The authors emphasise that the findings are associative rather than causal and call for larger longitudinal and intervention studies to determine whether modifying these pathways can alter brain chemistry.
Source: Johnstone N et al. Empirical evidence for gut microbial influence on human brain neurochemistry via the gut-brain axis. Molecular Psychiatry (2026). DOI: 10.1038/s41380-026-03813-y
