Gut bacteria and depression: “Compelling” further support to the “gut brain axis” notion

14 Feb 2019 --- Researchers have established a correlation between depression and a group of neurotransmitter-producing bacteria found in the human gut, further expanding clinical evidence of the gut-brain axis. Interestingly, an inverse relationship between specific gut bacteria and brain activity in areas connected to depression were identified in the animal study. Published in Nature Microbiology, the findings could lead to the development of bacterial therapeutics for depression, including a growing role for probiotics, but significant work is first required, the researchers note.

Previous research has demonstrated a strong link between the gastrointestinal tract and the central nervous system – the “gut-brain axis.” There is also mounting evidence linking imbalances in the microbial species that make up the gut microbiome to a number of health problems including allergies, autoimmune disorders and psychiatric mood disorders. Probiotics have even been flagged as a potential avenue of treatment to alleviate bipolar and other psychiatric mood disorders by a Baltimore Sheppard Pratt Health System study.

The research team from the US Department of Energy’s (DOE) Argonne National Laboratory and Northeastern University 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 association of microbial GABA metabolism with mental health is highly compelling,” says Jack Gilbert, Group Leader for Microbial Ecology at Argonne. “The general ability of the microbiome to produce and/or consume GABA has not been as broadly described before and a bacterium dependent on GABA has never previously been reported.”

“There continues to be support that the microbiome may be involved with depression, but turning these scientific discoveries (which are mostly in animals) into treatments will take time. One thing that helps with that process is identification of potential targets the microbiome may influence, such as GABA, so these can be further tested,” Gilbert tells NutritionInsight.

KLE1738 had formerly appeared on the “most wanted list” of the National Institutes of Health (NIH), meaning that it had yet to be cultured despite its relative prevalence in the human gut. This has remained to be “an obstacle for understanding its biological role,” note the researchers.

The bacterium has also been detected in nearly 20 percent of the human gut microbiomes available in the Integrated Microbial Next Generation Sequencing Database.

The team discovered that KLE1738 required the presence of Bacteroides fragilis, a common human gut bacterium, to grow.

Link to depression
In the next research phase, the team explored the possible connection between Bacteroides fragilis 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 fragilis and functional connectivity in a part of the brain associated with elevated activity during depression. This means that lower abundance of Bacteroides fragilis was associated with high activity in that part of the brain and vice versa.

“A good first step is to repeat our findings in additional human cohorts, which we are actively exploring,” continues Strandwitz. “When it comes to depression, animal models are often difficult to translate, which is why we are excited about these human studies.”

“There also needs to be more work to understand generally how bacteria and/or GABA they produce may signal to the body, including the brain. Recent work suggests there are sensory neurons in the gut that are hard wired to the brain, but the signals transmitted along that path need to be further mapped out,” Gilbert says.

Recent work published in the journals Science and Cell have identified the presence of sensory neurons in the gut that are hard-wired to the brain. “It would be great to explore whether microbial GABA can act as a signal via that pathway,” says Anukriti Sharma, a co-author of the Nature Microbiology article and a Postdoctoral Scholar at Argonne.

Digestive health is an ongoing discussion and science continues to link a healthy microbiome to nearly every facet of health. The continuous media reporting on gut health has also helped stimulate consumer interest in probiotics. The gut health platform offers a wealth of opportunities to formulators, but due to regulatory demands and increasing consumer scrutiny, a clear view of how to navigate this space is vital. https://www.nutritioninsight.com/news/navigating-the-digestive-health-space-probiotic-strain-specificity-and-microbiome-key-to-future-npd.html