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A research team is studying the compelling connection between one of the most NIH-researched bacteria and mental health.
The researchers correlated depression with a group of neurotransmitter-producing bacteria found in the human gut.
The research team at Argonne National Laboratory of the US Department of Energy (DOE) of Northeastern University and other universities established the connection by first isolating the KLE1738, a bacterium that surprisingly depends on a chemical acid of the brain called gamma-aminobutyric acid (GABA).
"The badociation of microbial GABA metabolism with mental health is very convincing," said Jack Gilbert, head of the Microbial Ecology Group at Argonne, who was also appointed to the faculty at the university. from California to San Diego, Department of Pediatrics and Scripps Institution of Oceanography. "The general ability of the microbiome to produce and / or consume GABA has not been described as broadly before, and a GABA-dependent bacterium has never been reported."
Gilbert and 18 co-authors published their conclusions on December 10, 2018, in Microbiology of nature.
"Because of its unique growth needs, no one else has reported a growth of KLE1738," said Philip Strandwitz, lead author of the article and postdoctoral researcher at the Northeastern University's Antimicrobial Discovery Center. Strandwitz and his colleagues proposed the name Evtepia gabavorous for KLE1738. They will describe the bacteria in more detail in a future publication.
KLE1738 was formerly on the "Most Wanted List" of the National Institutes of Health, which means that it had not yet been cultured, despite its relative prevalence in the human intestines. The bacterium has been detected in up to 20% of human intestinal microbiomes available in the integrated next generation microbial sequencing database.
The gut microbiota, all the microorganisms present in this habitat, affects many important functions, including the immune response and the nervous system. Nevertheless, many microorganisms residing in the human gut remain uncultivated, which the research team described as "an obstacle to understanding their biological roles" in the world. Microbiology of nature article.
More of these microorganisms probably remain uncultivated because they require essential growth factors provided by neighboring bacteria in their natural environment, but not under artificial laboratory conditions. During a thorough selection process, the team found that KLE1738 required the presence of Bacteroides fragilis, a common intestinal bacteria, to develop.
Further biobadays and purification have made it possible to isolate GABA as a growth factor produced by Bacteroides fragilis. GABA was in fact the only nutrient tested in the experiments that supported the growth of KLE1738.
During the next phase of research, the team explored the possible link between Bacteroides and depression. Stool samples and measurements of brain activity by functional magnetic resonance imaging were collected in 23 subjects with clinically diagnosed depression.
Researchers found an inverse relationship between relative abundance of fecal stool Bacteroidesand functional connectivity in a part of the brain badociated with high activity during depression. This means that the low abundance of Bacteroides was badociated with high activity in this part of the brain, and vice versa.
"A good first step is to repeat our discoveries in additional human cohorts, which we are actively exploring," Strandwitz said in his later research. "With regard to depression, animal models are often difficult to translate, which is why we are so enthusiastic about human studies."
Recent work published in journals Science and Cell have identified the presence of sensory neurons in the intestine that are wired to the brain. "It would be good to investigate whether microbial GABA can act as a signal via this pathway," said Anukriti Sharma, co-author of the article on Nature Microbiology and postdoctoral fellow at Argonne.
Strandwitz and co-author Kim Lewis, a prominent Northeastern University professor, founded a biotechnology company, Holobiome, to develop microbiome-based therapies that target diseases of the nervous system. Gilbert is a member of the scientific advisory board of the company. More research is needed before treatment can be developed for people with depression.
"Significant work needs to be done to begin validating the link between microbial GABA producers and depression," Strandwitz said. "And secondly, if it is validated, identify the right approach to develop a bacterial intervention – or some kind of intervention – as a therapeutic."
This study was funded by the National Institutes of Health and the National Institute of General Medical Sciences.
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