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Microbiome linked to depression in a groundbreaking Benelux study

This article is republished with kind permission from Biovox. The original article can be found here.

The microbiome had been at the forefront of a lot of research and news in the past few years. Now, a new study published in Nature Microbiology has linked specific microbiome changes with depression and quality of life. The largest of its kind to-date, the research was made possible by over 2000 participants from the Flemish Gut Flora Project and the Dutch LifeLines DEEP project. The results may lead to novel therapies for people suffering from this debilitating mental illness.

Studies on the function of our microbiome have been growing exponentially the past ten years. Of all the research being conducted, some of the most fascinating and difficult to comprehend has been the work on the gut-brain axis. The idea that your bowel bacteria is somehow affecting your mind might be hard to believe, but that is exactly what this new study supports. BioVox spoke to Prof. Jeroen Raes (VIB/KU Leuven), driving force behind the Flemish Gut Flora Project, and Mireia Vallès-Colomer, the lead author of the recent Nature Microbiome paper.

What motivated this research?

Raes: “There was an increasing stream of research in animal models, mostly in mice, suggesting a link between the gut microbiota and behavioral changes. But mice are not men; these models, especially for complex conditions like mental illness, are imperfect. We thought it was vital to validate the suspicions of a microbiome-mental health link in humans.

Vallès-Colomer: “The gut-brain axis has been proposed as a communication system between the microbiota and the brain for a while. There has been quite some evidence in animal models showing different mechanisms: we know that there is neural signaling between the gut and brain, mainly through the vagus nerve, but there may also be other pathways like the neuro-endocrine system or changes triggered by inflammation. These are all hypotheses though.

Raes: “Yes, the reality is: we know that the microbiomes in our gut are communicating with our central nervous system, but we don’t know how. If you look at the microbiome literature on the brain-axis from the last few years, 60% of the papers published are review articles, not research articles. Everyone is philosophizing and hypothesizing about what the mechanisms might be, but the answers are yet to come.”

How did you conduct this study?

Vallès-Colomer: “We studied the microbiome of 1000 people enrolled in the Flemish Gut Flora Project by using DNA sequencing to determine the bacterial composition of stool samples. We then compared the results of 120 clinically depressed participants, that had been diagnosed with depression or had done poorly on a quality of life survey, with the rest.

We then validated our results with a further analysis of 1000 people from the Dutch LifeLines DEEP project, making this one of the most comprehensive studies on the link between microbes and mental health ever conducted. And, finally, we validated the results yet again in a small cohort of severely clinically depressed patients at UZ Leuven.”

Raes: “This is what sets this study apart from others in the field: the scale and rigor with which it has been performed. We’ve worked with data from large cohorts. We’ve found our signals and we’ve meticulously validating them.

These kinds of signals are difficult to find and are often plagued by interfering factors. We went through a lot of effort to rule out confounding variables, allowing us to be very confident with the results we found.”

Mireia Valles Colomer in the lab

And what did you find?

Raes: “What we found were the strongest results to-date showing that a person’s microbiota can influence their mental health.”

Vallès-Colomer: “Indeed: we found that some bacterial strains, Dialister and Coprococcus, had reduced abundancies in patients with depression. We also found Coprococcus and another bacterial strain, Faecalibacterium, in increased amounts in people who scored higher on their quality of life surveys. These bacteria are known to produce butyrate, a substance which has anti-inflammatory effects in the colon, which may be a clue to their association with mental health.

We also developed a tool to assess the metabolism of neurochemicals in the gut (neurotransmitters and neuroactive compounds such as serotonin, GABA and dopamine). This allowed us to develop the first ever catalogue of microbial neuroactivity, where we found that a metabolite of the neurotransmitter dopamine produced by gut microbes was positively associated with good mental health.”

Could these discoveries lead to a new type of therapy for depression?

Raes: “Resolving the microbiome-brain connection might lead to novel therapies, yes.  Indeed, there is already research being done into potential microbiome solutions for mental health issues. However, depression is incredibly complex and multifactorial. Any treatment of the condition should therefore also be multifaceted: a combination of psychotherapy, classic antidepressants and perhaps future gut-modulatory medication.”

Vallès-Colomer: “This study was an association study; our next step will be to establish causality. Once we know more, we will try to develop strategies to modulate the composition of the microbiome; to see if we can restore a healthier bacterial community that complements other forms of treatment and helps us combat depression.”

It feels silly to ask, but why the link? Why can our gut microbes affect our mood so dramatically?

Raes: “When we look at gut bacteria and we consider their neuroactive potential (whether they are able to produce compounds that can interact with our nervous system), what we see is that almost all the bacteria in the gut are able to produce at least one type of neurotransmitter. If we compare those capabilities to bacteria which you find in the outside world, in the soil or water for example, you see that that capacity is almost entirely absent.

Gut bacteria have, somehow, specifically acquired the ability to talk to our nervous system. If you take that one step further, you can think about it in an evolutionary context: our gut bacteria have learned to talk to us while living in symbiosis with us. I think that is incredible!”

The agenda for the upcoming 7th Microbiome R&D & Business Collaboration Forum: USA is full of presentations on topics on the frontier of microbiome research and industry. Download the agenda here.

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