Researchers at Baylor College of Medicine & Texas Children's Hospital have recognized commensal bacteria in the human intestine that produce a neurotransmitter that may play a role in treating or preventing inflammatory bowel diseases (IBD) such as Crohn's disease.
Karina Pokusaeva, a researcher on the study and a member of the laboratory of James Versalovic,says, " We identified the first bifidobacterial strain, Bifidobacterium dentium, which is capable of secreting large amounts of gamma-aminobutyric acid (GABA). This molecule is a major inhibitory neurotransmitter in the central & enteric nervous systems."
GABA (gamma-aminobutyric acid) is one of the chief inhibitory neurotransmitters in the human central nervous system. It plays a role in regulating pain & some pain relieving drugs currently on the market act by targeting GABA receptors on neural cells.
Pokusaeva and her colleagues were interested in understanding the role the human microbiome might play in pain & scanned the genomes of potentially beneficial intestinal microorganisms, identified by the Human Microbiome Project, for evidence of a gene that would allow them to create GABA.
Pokusaeva says, "Lab analysis of metagenomic DNA sequencing data allowed us to demonstrate the microbial glutamate decarboxylase encoding gene which is extremely abundant in intestinal microbiota as compared to other body sites. One of the most prolific producers of GABA was B. dentium, which appears to secrete the compound to help it survive the acid environment."
In addition to its pain altering properties, GABA may also be capable of reducing inflammation. Recent studies have shown that immune cells called macrophages also possess GABA receptors. When these receptors were activated on the macrophages there was a decrease in the production of compounds responsible for inflammation.
Pokusaeva says that the lab was interested to explore if GABA produced by intestinal human isolate B. dentium could have an effect on GABA receptors present in immune cells. Together with their collaborators Dr. Yamada & Dr. Lacorazza they found that when the cells were exposed to secretions from the bacteria, they exhibited increased expression of the GABAA receptor in the immune cells.
While the findings are preliminary, they suggest the possibility that B. dentium and the compounds it secretes could play a role in reducing inflammation associated with inflammatory bowel diseases (IBD).
Pokusaeva says that the next step is to conduct in vitro experiments to determine if the increased GABAA expression correlates with a decrease in production of cytokines associated with inflammation. GABAA receptor signaling may also contribute to pain signaling in the gut and may somehow be involved in abdominal pain disorders.
Pokusaeva says, "Our preliminary findings suggest that Bifidobacterium dentium could potentially have an inhibitory role in inflammation; however more research has to be performed to further prove our hypothesis."
11 JUly 2012