Dietary patterns influence the in silico GABA production capacity of Bifidobacterium adolescentis HD17T2H and other human gut bacteria

Gamma-aminobutyric acid (GABA) is a neurotransmitter that inhibits neuronal excitability and also affects mucosal function and gut motility. Importantly, while the gut microbiome is a known source of GABA, little is known about the production capacities of its specific members. In our study, we investigated in silico how 11 predefined diets influence GABA production by Bifidobacterium adolescentis HD17T2H, an important GABA producer among bifidobacteria within the human gut microbiota. We show that the GABA production potential of B. adolescentis strain HD17T2H varies considerably across diets, with the vegetarian diet showing the highest potential and the ketogenic diet the lowest. Further, we analysed which specific compounds raised GABA production. Our in silico predictions revealed that carbohydrates and nitrogen-rich compounds, such as amino acids, strongly increase GABA production. We also analysed personalised nutritional data from a human cohort (Kiel cohort), in an in silico approach. In doing so, we found 87 potent GABA-producing strains across 47 bacterial genera, including Burkholderia, Pseudomonas, and Delftia, suggesting that not only commensals but also bacterial pathogens contribute to GABA production. Thus, our modelling approach highlights that nutrient availability is a central determinant of bacterial GABA production.