Gut Microbiome Research Is Advancing by Leaps and Bounds

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The first population-level study on the correlation between mental health and gut microbiome—based on data from over a thousand individuals enrolled in the Flemish Gut Flora Project (FGFP)—is available online today. FGFP is one of the largest studies on gut flora in the world and offers potentially groundbreaking empirical evidence about human gut microbiota and microbiome.

Recently, researchers at VIB-KU Leuven in the Netherlands (who oversee FGFP) pinpointed specific gut bacteria that correlate positively or negatively with mental health and quality of life.

The paper, “The Neuroactive Potential of the Human Gut Microbiota in Quality of Life and Depression,” was published online February 4 in the journal Nature Microbiology. This study offers valuable clues about specific gut microbiome colonies that may produce neuroactive compounds.

For this pioneering research, the Dutch microbiologists affiliated with the VIB-KU Leuven Center for Microbiology analyzed the ability of over 500 gut bacteria isolated from the human gastrointestinal tract to produce neuroactive compounds. To the best of my knowledge, these findings from the Jeroen Raes Lab represent one of the very first neuroactivity-related gut microbiome catalogs.

Most notably, Raes and colleagues identified that two bacterial genera, Coprococcus spp. and Dialister, were consistently depleted in individuals with clinical depression, regardless of whether the study participant was taking antidepressants. On the flip side, the authors said, "Butyrate-producing Faecalibacterium and Coprococcus bacteria were consistently associated with higher quality of life indicators."

The results of this research were corroborated by an independent cohort of 1,063 individuals from Dutch LifeLines DEEP and another cohort of clinically depressed patients at the University Hospitals Leuven in Belgium.

“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 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,” first author Mireia Valles-Colomer said in a statement. “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."

Proceed with Caution: Consuming Commercial Probiotics Can Backfire

Before reading further, there is an important caveat about probiotics and the misconception that taking over-the-counter supplements that may have a particular strain of so-called “good” gut bacteria might be some type of cure-all. For example, please do not interpret the preliminary finding by Valles-Colomer et al. (2019) that depleted levels of Dialister are correlated with depression as some type of prescriptive advice to seek out a generic probiotic with this bacteria as a hypothetical microbiome-based way to keep depression at bay. This would be reckless—bad advice!

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The gut microbiome ecosystem is extraordinarily complex and influenced by countless factors that scientists are just beginning to understand. Additionally, for some people, consuming commercially mass-produced probiotics can backfire. (see “Unexpected Findings Cause Scientists to Rethink Probiotics," “In a Brain Fog? Probiotics Could be the Culprit,” and “Back-to-Back Studies on Probiotics Set Off Alarm Bells.”)

A few days ago, the New York Times published an article by Carl Zimmer, “Germs in Your Gut Are Talking to Your Brain. Scientists Want to Know What They’re Saying.” that has been trending on their ‘Most Emailed’ list all week. Over the past few years, I’ve reported extensively on the bidirectional microbiome-gut-brain axis and vagus nerve. (see here, here, here, here, here.)

In his recent Times article on the gut-brain axis and microbiome research, Zimmer writes,

“Research continues to turn up remarkable links between the microbiome and the brain. Scientists are finding evidence that microbiome may play a role not just in Alzheimer’s disease, but Parkinson’s disease, depression, schizophrenia, autism and other conditions. As intriguing as this sort of research can be, it has a major limitation. Because researchers are transferring hundreds of bacterial species at once, the experiments can’t reveal which in particular are responsible for changing the brain. Now researchers are pinpointing individual strains that seem to have an effect.”

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The Jan. 28, 2019 article in the Times doesn’t reference the new study published today in Nature Microbiology that identified the above-mentioned gut microbiome with neuroactive potential. That said, the latest findings from the Raes Lab at VIB-KU Leuven serve as Exhibit A of ‘researchers pinpointing individual strains that seem to have an effect’ and are part of a “microbiome and the brain” timeline I do my best to keep updated in real-time as a blogger.

Source: Flemish Gut Flora Project (FGFP)/Raes Lab (VIB-KU Leuven)

“The relationship between gut microbial metabolism and mental health is a controversial topic in microbiome research,” Raes said in a statement. “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.”

For the next phase of this research, Jeroen Raes and his team are getting ready for another sampling round of the Flemish Gut Flora Project that will begin soon. The FGFP is currently limited to Belgian participants. However, if you don’t live in Belgium, and are interested in joining this study when it goes international, please send your contact information to gutflora@vib.be.

Groundbreaking Study Identifies Over 100 Previously Unknown Species of Human Gut Bacteria

In addition to the recent study by Valles-Colomer et al. (2019), another study by a different international team of researchers (published today) has identified and isolated 105 novel species of human gut bacteria. This paper, "A Human Gut Bacterial Genome and Culture Collection for Improved Metagenomic Analyses," was published online Feb. 4 in Nature Biotechnology.

"This study has led to the creation of the largest and most comprehensive public database of human health-associated intestinal bacteria. The gut microbiome plays a major in health and disease. This important resource will fundamentally change the way researchers study the microbiome," first author Samuel Forster of the Wellcome Sanger Institute and Hudson Institute of Medical Research in Australia said in a statement.

These findings are Exhibit B of 'researchers [who] are pinpointing individual strains that seem to have an effect' shared in this post.

The authors (Forster et al., 2019) explain the significance of this discovery, "We present the Human Gastrointestinal Bacteria Culture Collection (HBC), a comprehensive set of 737 whole-genome-sequenced bacterial isolates, representing 273 species (105 novel species) from 31 families found in the human gastrointestinal microbiota. The HBC increases the number of bacterial genomes derived from human gastrointestinal microbiota by 37%. The resulting global Human Gastrointestinal Bacteria Genome Collection (HGG) classifies 83% of genera by abundance across 13,490 shotgun-sequenced metagenomic samples, improves taxonomic classification by 61% compared to the Human Microbiome Project (HMP) genome collection and achieves subspecies-level classification for almost 50% of sequences."

Senior author, Trevor Lawley, also of the Wellcome Sanger Institute, said, “This culture collection of individual bacteria will be a game-changer for basic and translational microbiome research. By culturing the unculturable, we have created a resource that will make microbiome analysis faster, cheaper and more accurate and will allow further study of their biology and functions. Ultimately, this will lead us towards developing new diagnostics and treatments for diseases such as gastrointestinal disorders, infections and immune conditions.”