GABA Production by Human Intestinal Bacteroides spp.: Prevalence, Regulation, and Role in Acid Stress Tolerance

The high neuroactive potential of metabolites produced by gut microbes has gained traction over the last few years, with metagenomic-based studies suggesting an important role microbiota-derived γ-aminobutyric acid (GABA) in modulating mental health. Emerging evidence revealed presence glutamate decarboxylase (GAD)-encoding gene, a key enzyme to produce GABA, prominent human intestinal genus Bacteroides . Here, we investigated GABA production culture and metabolic assays combined comparative genomics phylogenetics. A total 961 genomes were analyzed silico 17 metabolically genetically diverse isolates representing 11 species screened vitro Using model organism thetaiotaomicron DSM 2079, determined kinetics, its impact on milieu pH, assessed mitigating acid-induced cellular damage. We showed that GAD-system consists at least four highly conserved genes encoding GAD, glutaminase, glutamate/GABA antiporter, potassium channel. demonstrated prevalence among 90% all (96% only) harboring 16 strains producing (ranging from 0.09 60.84 mM). identified glutamine as precursors production, is regulated acts protective mechanism against stress , cell death preserving activity. Our data also indicate might represent only amino acid-dependent tolerance system Altogether, our results suggest contribution regulation GABAergic gut.