Researchers pinpoint ‘depressing’ gut microbe with potential for psychobiotics

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Summary: Examining the gut microbiome of patients with major depressive disorders, researchers identified the presence of the bacterium Faecalibacterium prausnitzii as responsible for the functional discrepancies between healthy individuals and patients with MDD.

Source: Skolkovo Institute of Science and Technology

In a three-year study, researchers from Skoltech, Vavilov Institute of General Genetics of RAS, Moscow Mental-Health Clinic No. 1, named after NA Alexeev, and the Serbsky Federal Medical Research Center of Psychiatry and Narcology examines how gut microbes invade patients with major depressive disorder differ from those in mentally healthy individuals.

After analyzing all of the genes present in the gut microbiome, the team pinpointed a specific bacterium — Faecalibacterium prausnitzii — responsible for the largest functional discrepancy between the healthy and depressed datasets.

The results, promising for express mental health diagnostics and psychobiotic medications, are reported in biomedicine.

“If you know which genes are more or less represented in depressed patients compared to the healthy population and which bacteria are responsible for this, you can try two things,” commented the study’s first author, Skoltech Bio Research intern Alexey Kovtun.

“First, analysis of the faecal microbiota can be used as a complementary tool in the diagnosis of the mental disorder. Second, you can try to develop drugs that ‘normalize’ the gut microbiome in depressed patients.”

In order to identify “depressing” intestinal germs, the researchers carried out so-called full metagenome analyses. That is, they obtained and sequenced the entire bacterial DNA from fecal samples from a cohort of patients diagnosed with major depressive disorder and a cohort of mentally healthy individuals.

“The result is that we know what genes and types of bacteria are present in the microbiome of each group and how well represented they are,” Kovtun said.

The next step is to identify the set of genes that differ significantly between the healthy individuals and those with the mental disorder, and zoom in on those specific genes to find out which of the bacteria that carry them is more depressed in the microbiome Patients are actually over- or under-represented.

“One particular bacterium really stood out,” Kovtun explained. “It’s called Faecalibacterium prausnitzii and is much less common in the intestines of patients with a major depressive disorder. We linked it to three grossly underrepresented gene groups in the microbiome metagenome of these patients.”

In order to identify “depressing” intestinal germs, the researchers carried out so-called full metagenome analyses. The image is in the public domain

The first of the three remarkable sets of genes is involved in the production of the hormone melatonin, which regulates the sleep-wake cycle. The second is related to the formation of the classic neurotransmitters glutamate and gamma-aminobutyric acid. The third consists of several genes responsible for the synthesis of short-chain acids, deficiency of which has been linked to depression.

According to the authors of the publication, the microbe whose role the study highlights – Faecalibacterium prausnitzii – has increasingly attracted the attention of researchers in connection with the development of treatment options and diagnostic approaches for various diseases based on specific bacterial strains. Experts are enthusiastic about this bacterium.

“Hopefully, it could prove to be a useful target for express test kits to diagnose mental disorders and psychobiotic drugs that promote mental well-being by harmonizing the patient’s microbiome,” Kovtun added.

“We hear a lot about prebiotics and probiotics — well, psychobiotics could be the next big thing, and our team is part of the global effort to make them a reality.”

About this microbiome and news from depression research

Author: press office
Source: Skolkovo Institute of Science and Technology
Contact: Press Office – Skolkovo Institute of Science and Technology
Picture: The image is in the public domain

Original research: Open access.
“Changes in composition and neurometabolic profile of human gut microbiota in major depressive disorder” by Alexey S. Kovtun et al. biomedicine


abstract

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Changes in the composition and neurometabolic profile of the human gut microbiota in major depressive disorder

Major depression (MDD) is one of the most widespread mental illnesses worldwide. Factors causing the pathogenesis of MDD include the gut microbiota (GM), which interacts with the host through the gut-brain axis.

Previous studies of GM in MDD patients used 16S rRNA sequencing, which provided information about composition but not function.

In our study, we analyzed full metagenome sequencing data to assess changes in both the composition and functional profile of GM.

We examined the GM of 36 MDD patients compared to 38 healthy subjects. Comparative taxonomic analyzes showed reduced frequencies of Faecalibacterium prausnitzii, Roseburia hominisand Roseburia intestinalisand increased fills of Escherichia coli and Ruthenibacterium lactatiformans in the GM of MDD patients.

We observed decreased levels of bacterial genes encoding key enzymes involved in the production of arginine, asparagine, glutamate, glutamine, melatonin, acetic, butyric and conjugated linoleic acids, and spermidine in MDD patients.

These genes generated signature pairs with Faecalibacterium prausntizii and correlated with decreased levels of these species in the GM of MDD patients.

These results demonstrate the potential impact of the identified biomarker bacteria and their metabolites on the pathogenesis of MDD and should be confirmed in future metabolomic studies.

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