The association of the GABA (gamma amino butyric acid) system with psychiatric disorders including depression and anxiety is compelling that it has long been described as one of the most important molecules associated with mental health. In fact, advances in pharmacological and molecular genetic tools have provided greater insight into the correlation between GABA and behavioral characteristics.
Recently, scientists from the U.S. Department of Energy’s (DOE) Argonne National Laboratory, North-eastern University discovered a possible link between the KLE1738, a gut bacterium, and depression. The researchers named the bacterium Evtepia gabavorous. This discovery is actually one of its kind since the ability of microorganisms to metabolize or synthesize GABA has not been as broadly described as before. In fact, the researchers have affirmed that a bacterium dependent on the GABA system has never been reported in the literature. Furthermore, many microorganisms residing in the human gut has not been cultured due to their unique growth requirements.
Again, gut bacteria exist in a unique form of symbiosis within the human gut where a certain bacterium may require key growth factors that are provided by neighboring bacteria in their natural environments, but which are difficult to simulate under laboratory conditions. The team was able to discover that KLE1738 required the presence of Bacteroides fragilis, a common human gut bacterium to grow. This is due to the dependence of the bacterium on a chemical in the brain called gamma-amino butyric acid (GABA) and its complex growth requirements. Through extensive biological testing and purification, the researchers were able to discover that GABA was, in fact, the growth factor produced by Bacteroides fragilis.
In the next research phase, the researchers were able to discover an inverse relationship between the relative abundance of fecal Bacteroides and its functional connectivity with certain regions of the brain that are associated with increased activity during depressive episodes. That is, low abundance of Bacteroides was associated with the high activity in that part of the brain and vice versa. The researchers are prepared to repeat their findings in human subjects to validate the link between microbial GABA producers and depression.
This will have a potential in the development of more effective therapeutic agents for the management of depression. Many pharmacological agents that are available for the management of depression are not without side effects and potential drug-drug interactions. Furthermore, their safety profile has not been well established. For instance, the tricyclic antidepressants have side effects not limited to blurred vision, dry mouth, constipation, weight gain (or even weight loss), low blood pressure on standing, rash and cardiac arrhythmias in some cases. Furthermore, the monoamine oxidase inhibitors include nausea, diarrhea, drowsiness, and insomnia. These side effects often influence compliance and the outcome of therapy for patients suffering from a wide range of neuropsychiatric disorders.
It is hoped that this research if validated, there will be opportunities to identify the right approach to develop appropriate therapies and useful formulations for the management of depression.