Two new studies published in Nature Communications offer some of the strongest evidence to date for a relationship between depression and gut bacteria. The research does not claim bacteria in the gut directly causes depression, but does suggest a strong correlation that could inform novel diagnostic biomarkers for the mood disorder.
The idea our gut microbiome can influence our mood is not new. Researchers have uncovered plenty of fascinating gut-brain associations suggesting the bacterial populations in the gut are linked to depressive behavior, including one compelling mouse study that found behavioral characteristics of depression could be transferred to healthy animals via fecal transplants.
This new research arose out of an ongoing study dubbed HELIUS (Healthy Life in an Urban Setting), a project that is following 23,000 people in Amsterdam. The HELIUS project is particularly focused on the health differences between people of different ethnicities living in the same urban environments. So for microbiome researchers, it offers a unique opportunity to explore how ethnicity might influence the relationship between gut bacteria and depression.
The first study, led by researchers from the University of Amsterdam, looked at around 3,000 participants in the HELIUS project, spanning six different ethnicities (Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish, Moroccan). Although the primary aim of the study was to look at general associations between the microbiome and depression, the unique ethnic mix of participants allowed for the first look at whether ethnic disparities influence the gut-mood relationship.
Overall, the study found consistent associations between general microbial diversity and depression, regardless of ethnicity. Essentially, the more diverse an individual's gut bacterial population the less likely they were to experience depression.
Interestingly, the research did detect disparities in depression risk between ethnicities but these differences could be accounted for by individual variations in a person's microbiome composition. Jos Bosch, one of the researchers working on the study, speculates dietary differences between ethnic groups living in the same urban environment could be influencing the microbiome-depression relationship.
"The substantial ethnic differences in depression do indeed appear to be related to ethnic differences in the microbiome," said Bosch. "We don't know exactly why this is yet. This association was not caused by differences in lifestyle such as smoking, drinking, weight or exercise, and merits further investigation. For example, diet could play a role."
The second study zoomed in more specifically on the gut bacterial species that could be associated with depression. First, stool samples of around 1,000 subjects from an ongoing population health study in Rotterdam were closely analyzed to track correlations between specific bacteria and depression symptoms. Thirteen bacterial types were directly associated with symptoms of depression.
"The study found convincing, replicable evidence for an increase in Sellimonas, Lachnoclostridium, Hungatella and decrease in Ruminococcus, Subdoligranulum, LachnospiraceaeUCG001, Eubacterium-ventriosum and Ruminococcusgauvreauiigroup in the guts of individuals with more depressive symptoms," reads a statement from Oxford Population Health, a collaborator on the study. "The discovery of the association between Sellimonas and symptoms of depression is the most significant novel finding of this study. Species of bacteria belonging to the Sellimonas genus are involved in various inflammatory diseases and may be relevant for the inflammation seen in patients with depression."
These findings from the Rotterdam cohort were subsequently validated in a group of 1,500 subjects from the HELIUS study. This affirmed the relationship between depression and the microbiome in one of the largest sample sizes of humans to date.
Of course, the million-dollar question is whether these gut microbes are actually contributing to a person's depression, or are other factors relating to depression cause these microbiome changes?
Najaf Amin, co-author on the Oxford study, said the causal relationship is still unclear. Some of the bacteria identified in the study are known to synthesize several key brain neurotransmitters relating to mood and depression, so it is entirely plausible to speculate the microbiome plays a causal role in depression. However, Amin also suggests it is just as plausible to suggest depression leads to other physiological changes that subsequently transform the microbiome.
Perhaps the more immediate outcome from these studies is the finding that there may be a kind of universal gut bacteria signature for depression. This means it could be possible for doctors to objectively diagnose depression in patients by using microbiome biomarkers.
"What we are looking for is to identify the bacteria that associate with major depression," Amin said. "This will help us in identifying a biomarker for depression that can be used as an objective measurement in identifying cases – which is lacking at the moment for depression."
The Amsterdam and Oxford studies were recently published in Nature Communications.