The gut/brain connection grew much stronger this week with the publication of the first population-level study on the link between gut bacteria and mental health. The research identified specific gut bacteria linked to depression and provides evidence that a wide range of gut bacteria can produce neuroactive compounds.

The study, led by Sara Vieira-Silva, PhD, and Jeroen Raes, PhD, from the department of microbiology and immunology, KU Leuven-University of Leuven and VIB Center for Microbiology, Belgium, studied the relation between gut bacteria and quality of life and depression. The authors combined fecal microbiome data with general practitioner diagnoses of depression from 1,054 individuals enrolled in the Flemish Gut Flora Project.

In the paper titled, “The neuroactive potential of the human gut microbiota in quality of life and depression,” published in Nature Microbiology, specific groups of microorganisms were identified that positively or negatively correlated with mental health. The authors found that Coprococcus and Dialister were consistently depleted in individuals with depression, regardless of antidepressant treatment. The results were validated in an independent cohort of 1,063 individuals from the Dutch LifeLinesDEEP cohort and in a cohort of clinically depressed patients at the University Hospitals Leuven, Belgium.

“The relationship between gut microbial metabolism and mental health is a controversial topic in microbiome research. The notion that microbial metabolites can interact with our brain—and thus behavior and feelings—is intriguing, but gut microbiome-brain communication has mostly been explored in animal models, with human research lagging behind,” noted Raes. He adds that in their population-level study, “we identified several groups of bacteria that co-varied with human depression and quality of life across populations.”

Previously, Raes’s team identified a microbial community constellation or enterotype characterized by low microbial count and biodiversity that was observed to be more prevalent among Crohn’s disease patients. In their current study, they surprisingly found a similar community type to be linked to depression and reduced quality of life.

“This finding adds more evidence pointing to the potentially dysbiotic nature of the Bacteroides2 enterotype we identified earlier. Apparently, microbial communities that can be linked to intestinal inflammation and reduced well being share a set of common features,” noted Raes.

The authors also created a computational technique allowing the identification of gut bacteria that could potentially interact with the human nervous system. They studied genomes of more than 500 bacteria isolated from the human gastrointestinal tract in their ability to produce a set of neuroactive compounds, assembling the first catalog of neuroactivity of gut species. Some bacteria were found to carry a broad range of these functions.

The authors wrote that “gut–brain module analysis of fecal metagenomes identified the microbial synthesis potential of the dopamine metabolite 3,4-dihydroxyphenylacetic acid as correlating positively with mental quality of life and indicated a potential role of microbial γ-aminobutyric acid production in depression.”

“Many neuroactive compounds are produced in the human gut,” said Mireia Valles-Colomer, a graduate student and first author on the paper. “We wanted to see which gut microbes could participate in producing, degrading, or modifying these molecules. Our toolbox not only allows to identify the different bacteria that could play a role in mental health conditions, but also the mechanisms potentially involved in this interaction with the host.”

These findings resulted from bioinformatics analyses and will need to be confirmed experimentally, however, they will help direct and accelerate future human microbiome-brain research. The research team is now preparing another sampling round of the Flemish Gut Flora Project that is going to start next spring, five years after the first sampling effort.

A second paper was published recently that will bolster the research in the gut microbiome community. The study from the Wellcome Sanger Institute, Hudson Institute of Medical Research, Australia, and EMBL’s European Bioinformatics Institute, has created the most comprehensive collection of human intestinal bacteria to date. This Human Gastrointestinal Bacteria Culture Collection (HBC) was published in a paper titled, “A human gut bacterial genome and culture collection for improved metagenomic analyses,” in Nature Biotechnology and describes the discovery and isolation of more than 100 completely new species of bacteria from healthy people’s intestines. This new resource will allow scientists to detect which bacteria are present in the human gut more accurately and faster than ever before.

These papers, taken together, are part of the movement that is providing the foundation that will, eventually, lead to the development of new ways to treat diseases such as gastrointestinal disorders, infections, and immune conditions.

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