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A gut feeling for mental health

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07 February 2019

​T​he first population-level study on the link between gut bacteria and mental health identifies specific gut bacteria linked to depression and provides evidence that a wide range of gut bacteria can produce neuroactive compounds. Researchers of the department of Genetics of the UMCG published this work, together with and led by the team of Jeroen Raes of VIB-KU Leuven, in the scientific journal Nature Microbiology.

In their manuscript entitled ‘The neuroactive potential of the human gut microbiota in quality of life and depression’ Raes and his team studied the relation between gut bacteria and quality of life and depression. The authors combined faecal microbiome data with general practitioner diagnoses of depression from 1,054 individuals enrolled in the Flemish Gut Flora Project. They identified specific groups of microorganisms that positively or negatively correlated with mental health. The authors found that two bacterial genera, 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 LifeLinesDEEP cohort - a study initiated by the Genetics department of the UMCG - and in a cohort of clinically depressed patients at the University Hospitals Leuven, Belgium.

The Leuven group was leading the data analysis, whereas the LifelinesDEEP cohort was used for the replication and conformation of results. Sasha Zhernakova, professor of Genetics at UMCG: ‘In the LifelinesDEEP dataset several unique measurements are available. Also, the analysis of gut microbiome in LifelinesDEEP is done by highly accurate metagenomics sequencing method, which allowed direct annotation of bacterial genes, relevant for the gut-brain axis’.

Prof Jeroen Raes (VIB-KU Leuven): ‘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 behaviour and feelings - is intriguing, but gut microbiome-brain communication has mostly been explored in animal models, with human research lagging behind. In our population-level study we identified several groups of bacteria that co-varied with human depression and quality of life across populations.’

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 catalogue of the neuroactivity of gut species. Some bacteria were found to carry a broad range of these functions.

Mireia Valles-Colomer (VIB-KU Leuven): ‘Many neuroactive compounds are produced in the human gut. We wanted to see which gut microbes could participate in producing, degrading, or modifying these molecules. Our toolbox not only allows us 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. For example, we found that the ability of microorganisms to produce DOPAC, a metabolite of the human neurotransmitter dopamine, was associated with better mental quality of life.’

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.

Read the publication in Nature Microbiology​.