GABA-Modulating Bacteria : Microbiome-Based Therapeutics for Depression?

Presenter: Philip Strandwitz

Research Category: Health Sciences
Student Type: Graduate
PI: Kim Lewis

The importance of the human gut microbiome (our gut bacteria) is hard to overstate — our intestinal inhabitants have been linked to numerous gastrointestinal diseases, including Crohn’s disease, obesity, and type II diabetes. While important, these connections are not surprising since they are digestive disorders. An exciting new development is the unanticipated link of the microbiome to mental health, with the microbiome being involved in brain development, mood, and behavior. 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. One isolate, KLE1738, 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 KLE1738. GABA is the major inhibitory neurotransmitter of the mammalian central nervous system, and decreased levels are associated with depression and anxiety. Genomic analysis of KLE1738 suggests an unusual metabolic map focused on consuming a single nutrient, GABA. Using growth of KLE1738 as a bioassay, a number of abundant members of the gut microbiome were found to be producers of GABA. We have also engineered one of the safest probiotics in the world, E. coli Nissle 1917, to produce GABA. By modulating levels of GABA modulating bacteria (by introducing our engineered E. coli Nissle 1917 strain or selectively targeting KLE1738), we may be able to design microbiome-based therapeutics to treat mental health disorders.