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GABA-modulating bacteria of the human gut microbiota.

TitleGABA-modulating bacteria of the human gut microbiota.
Publication TypeJournal Article
Year of Publication2019
AuthorsStrandwitz P, Kim KHyun, Terekhova D, Liu JK, Sharma A, Levering J, McDonald D, Dietrich D, Ramadhar TR, Lekbua A, Mroue N, Liston C, Stewart EJ, Dubin MJ, Zengler K, Knight R, Gilbert JA, Clardy J, Lewis K
JournalNat Microbiol
Volume4
Issue3
Pagination396-403
Date Published2019 Mar
ISSN2058-5276
Abstract

The gut microbiota affects many important host functions, including the immune response and the nervous system. However, while substantial progress has been made in growing diverse microorganisms of the microbiota, 23-65% of species residing in the human gut remain uncultured, which is an obstacle for understanding their biological roles. A likely reason for this unculturability is the absence in artificial media of key growth factors that are provided by neighbouring bacteria in situ. In the present study, we used co-culture to isolate KLE1738, which required the presence of Bacteroides fragilis to grow. Bioassay-driven purification of B. fragilis supernatant led to the isolation of the growth factor, which, surprisingly, is the major inhibitory neurotransmitter GABA (γ-aminobutyric acid). GABA was the only tested nutrient that supported the growth of KLE1738, and a genome analysis supported a GABA-dependent metabolism mechanism. Using growth of KLE1738 as an indicator, we isolated a variety of GABA-producing bacteria, and found that Bacteroides ssp. produced large quantities of GABA. Genome-based metabolic modelling of the human gut microbiota revealed multiple genera with the predicted capability to produce or consume GABA. A transcriptome analysis of human stool samples from healthy individuals showed that GABA-producing pathways are actively expressed by Bacteroides, Parabacteroides and Escherichia species. By coupling 16S ribosmal RNA sequencing with functional magentic resonance imaging in patients with major depressive disorder, a disease associated with an altered GABA-mediated response, we found that the relative abundance levels of faecal Bacteroides are negatively correlated with brain signatures associated with depression.

DOI10.1038/s41564-018-0307-3
Alternate JournalNat Microbiol
PubMed ID30531975
PubMed Central IDPMC6384127
Grant ListF32 GM108415 / GM / NIGMS NIH HHS / United States
R01 HG005824 / HG / NHGRI NIH HHS / United States