GABA Modulating Bacteria in the Human Gut Microbiome

Abstract

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Half of the bacterial species inhabiting the human intestinal tract will not grow in the laboratory. This is a significant unsolved problem, as our intestinal inhabitants have been linked to numerous gastrointestinal diseases, including Crohn’s disease, obesity, and type II diabetes. While important, these connections are perhaps not surprising since they are digestive disorders. An exciting new development is the unanticipated link of the microbiome to mental health, with the microbiome likely being involved in brain development, mood, and behavior, though specific mechanisms behind this communication are unknown. Previously, our group found that “uncultured” bacteria depend on neighboring “helper” bacteria for growth factors. In the present study, we used a similar co-culture approach to grow uncultured bacteria from human fecal samples, and successfully cultivated of a number of organisms found on the NIH’s Most Wanted Genome List. One isolate, Flavonifractor sp., required the presence of Bacteroides fragilis or Dorea longicatena for growth. Using bio-assay driven purification of B. fragilis supernatant, γ-aminobutyric acid (GABA) was identified as the growth factor of Flavonifractor sp. GABA is the major inhibitory neurotransmitter of the mammalian central nervous system, and decreased levels are associated with depression and anxiety. Genomic analysis of Flavonifractor sp. suggests an unusual metabolic map focused on consuming a single nutrient, GABA. Using growth of Flavonifractor sp. as a bioassay, a number of abundant members of the gut microbiome were found to be producers of GABA. These GABA-modulating bacteria may be affecting mental health by consuming or producing this important neurotransmitter.