Molecular psychiatryAug 25, 2026

Evidence that gut microbes may affect human brain chemistry through the gut-brain connection

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Aug 28, 2026

Abstract

Associations were observed between gut microbiome-derived neuroactive functional potential and brain neurotransmitter concentrations in healthy young females.

Microbial pathways related to GABA and glutamate synthesis and degradation were characterized through metagenomic profiling.
Region-specific links were found between microbial pathways and levels of GABA and glutamate in the brain's cortex.
Microbial glutamate degradation and inositol synthesis potential was associated with the excitatory/inhibitory balance in the inferior occipital gyrus.
Distinct associations were noted for additional pathways including GABA metabolism, p-cresol production, and short-chain fatty acid synthesis across different brain regions.
Exploratory analyses indicated potential connections between microbial functional potential and psychological factors such as anxiety, depressive symptoms, and sleep quality.

Simplified

The gut microbiome produces metabolites with potential neuroactive properties, many of which act locally within the gut. While preclinical studies suggest these microbial pathways can influence cognitive and emotional processes, human evidence remains limited. This study investigates associations between gut microbiome-derived neuroactive functional potential and in vivo brain neurotransmitter concentrations in healthy young females. Using proton magnetic resonance spectroscopy (¹H-MRS), we quantified GABA and glutamate levels in the dorsolateral prefrontal cortex (dlPFC), anterior cingulate cortex (ACC), and inferior occipital gyrus (IOG). Parallel metagenomic profiling characterised microbial functional potential for pathways related to the synthesis and degradation of GABA, glutamate, short-chain fatty acids (SCFAs), p-cresol, and inositol. Region-specific associations were observed between these microbial pathways and cortical GABA and glutamate levels, including excitatory/inhibitory (E/I) balance, a key marker of neuroplasticity and mental health. Notably, microbial glutamate degradation and inositol synthesis potential were associated with IOG E/I balance, while additional pathways including GABA metabolism, p-cresol production, and SCFA synthesis showed distinct associations across regions. Exploratory analyses also identified links between microbial functional potential and anxiety, depressive symptoms, and sleep quality. Together, these findings provide new human evidence that variation in microbial functional potential corresponds with regional cortical neurochemistry and psychological wellbeing, highlighting the gut-brain axis as a promising avenue for mechanistically informed microbiome-based- interventions.