Human gut bacterium reveals possible connection to depression

Research team studies the compelling connection between one of NIH's "most wanted" bacteria and mental health. Scientists have established a correlation between depression and a group of neurotransmitter-producing bacteria found in the human gut.

The research team from the U.S. Department of Energy's (DOE) Argonne National Laboratory, Northeastern University and elsewhere made the connection by first isolating the KLE1738, a bacterium that has a surprising dependency upon a brain chemical called gamma-aminobutyric acid (GABA).

The general ability of the microbiome to produce and/or consume GABA has not been as broadly described before, and a bacterium dependent on GABAhas never been reported. KLE1738 had previously appeared on the "most wanted list" of the National Institutes of Health, meaning that it had yet to be cultured, despite its relative prevalence in the human gut. The bacterium has been detected in nearly 20 percent of the human gut microbiomes available in the Integrated Microbial Next Generation Sequencing Database.

Gut microbiota, the entire collection of microorganisms found in that habitat, affect many important functions, including the immune response and the nervous system. Nevertheless, many microorganisims residing in the human gut remain uncultured, which the research team called "an obstacle for understanding their biological roles" in the Nature Microbiology article.

More such microorganisms probably remain uncultured because they require key growth factors that are provided by neighboring bacteria in their natural environments, but not under artificial laboratory conditions. During an extensive screening process, the team found that KLE1738 required the presence of Bacteroides fragilis, a common human gut bacterium, to grow.

Further biological testing and purification led to the isolation of GABA as the growth factor produced by Bacteroides fragilis. GABA was, in fact, the only nutrient tested during the experiments that supported the growth of KLE1738.

In the next research phase, the team explored the possible connection between Bacteroides and depression. Stool samples and functional magnetic resonance imaging measurements of brain activity were collected from 23 subjects suffering from clinically diagnosed depression.

The researchers found an inverse relationship between the relative abundance of fecal Bacteroides and functional connectivity in a part of the brain associated with elevated activity during depression. This means that low abundance of Bacteroides was associated with high activity in that part of the brain, and vice versa.

See: GABA-modulating bacteria of the human gut microbiota. Nature Microbiology

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology