As much as the microbiota are a crucial part of our immune system and regulate inflammation, they are also intrinsically linked with the hypothalamic pituitary axis and stress response system of the body. For those details, see this article:  The Gut-Brain Connection, Mental Illness, and Disease.

There’s a lot of data about irritable bowel and depression/anxiety, and more data about irritable bowel and the microbiota. But there is very little linking the microbiota directly to depression in humans, until this recent paper in Neurogastroenterology and Motility: Correlation between the human fecal microbiota and depression

In the paper, the fecal microbiota of 55 people were examined (37 patients diagnosed with depressive disorder, and 18 non-depressed controls). They call this sample “large.” In terms of number of people, I would say, not that large, but it terms of microbiota, we are talking 100 trillion per person, so maybe the largest study of depressed microbes in the history of scientific inquiry. This study was introductory, just seeing if there were some correlations between the type of microbiota in the gut and the symptoms of the host person. Exciting, right? So what did they find…let’s allow the paper to speak for itself here:

We found several correlations between depression and fecal microbiota. The correlations, however, showed opposite directions even for closely related Operational Taxonomic Units (OTUs), but were still associated with certain higher order phylogroups. The order Bacteroidales showed an overrepresentation [(etc etc)]…At low taxonomic levels, there was one clade consisting of five OTUs….

I have a biology degree and have read hundreds of papers about the microbiome, and I was flummoxed. Clearly we need a microbiota dictionary here:

OTU (Operational Taxonomic Unit): a species defined by DNA sequencing alone

Clade: a term coined in 1957 by Julian Huxley to refer to a group consisting of an ancestor and all of its descendants. 

So, to translate the results, we end up with several groups of related species of microbiota that have some similar features (for example, some of the genus Oscillibacter) and some similar biochemical effects being over or under represented in the subjects with depression. The main metabolic product of Oscillibacter is very much like the human antianxiety neurotransmitter GABA. Kinda interesting. 

Ultimately, the researchers identified over 1500 distinct OTUs amongst the sample of patients and controls, with the 100 most dominant species representing 62% of the microbiota found, with the number one species betting Bacteriodetes ovatus, represeting 4% of the total sample and found in 54 of the 55 individuals.

Depressed people didn’t tend to have a more or less robust or varied microbiota than the controls. There was a bit less Bacteriodales in the depressed individuals (the same is also true in obese individuals, correlated with depression), but there was no single species (OTU) of microbiota that one could say: “Ah ha! That bug is associated with depression!”

Instead, the researchers were able to find a combination of represented species that correlated highly with depression, so that if one overlaid that particular combo of species on the individuals, one could correctly identify those with depression 100% and 97% of the non-depressed controls. Antidepressant medication did not seem to influence this model. Impressive, no?

Well, maybe not. We’ve collected a sample of individuals here, we apply a multivariate analysis of their microbiota and backtrack to see if there is an association with depression symptoms, then retrack on the same samples…I would me more impressed if we could use the same model of microbiota on a whole different group of depressed patients and find we could diagnose depression with pretty much 100% sensitivity and specificity

Wow, that would be the holy grail of biological psychiatry right there. We already have some biological markers of depression…zinc levels, certain inflammatory cytokines…but a simple fecal sampling to diagnose depression…that would be amazing.

 The confusing thing about the dataset is that some closely related OTUs were associated with opposite groups…sibling species, if you will, some associated more with depressed individuals, some with non-depressed individuals. And with no single species lighting the way, we will have to focus more on the complex interactions between the species and how groups might be dominant over others. When the group individuals number 100 trillion, the math gets unwieldy pretty quickly.

In any event, the paper opens up a lot of interesting questions…plenty of meat for microbiome researchers to dig their teeth into. Diet, probiotics, antibiotics, and prebiotics can all alter the microbiome and might be reasonable candidates for treatments for depression. 

Copyright Emily Deans MD

Image credit: wikpedia (

You are reading

Evolutionary Psychiatry

On The Evolution of the Serotonin Transporter Gene

A gene that can modulate stress response may have big behavioral consequences.

Is Vulnerability to Stress Coded in Our Genes?

Serotonin genetic variation seems to modulate our stress response

All the Stars of Food and Mood

The best researchers in the world came together for ISNPR.