Is There A Connection Between Gut Bacteria And Depression?

It seems like every month we see a new study come out that describes yet another way in which we are deeply connected to and dependent on the bacteria that call our digestive tract home.

We've known for decades the critical role gut flora play in digestion, although we continue to learn more about how many nutrients are produced by our microbiome. [1] 

In more recent years, hundreds of studies have detailed the complex relationship between gut flora and immune function [2][3] as well as the influence our gut flora exerts on our endocrine (hormone) systems including the HPA axis [4] and sex hormones. [5]

A few months ago, a new and very intriguing chapter was added to this microbial story when researchers from Norway published a study examining correlations between specific bacterial species in the gut and clinical depression - in a study group of 37 clinically depressed patients and 18 control patients. [6]

Because of the influence gut flora exert on hormonal and immune systems, it's perhaps not a surprise that there would be a strong correlation between the microbiome and mental well-being. The real revelations in this article come from the correlation of a specific psychological condition with specific species of gut bacteria - as well as the examination of how some of these species might exert their influence on the brain.

Let's take a look at what the researchers learned, the limitations/problems with this information and (hopefully) how we can apply this information to our lifestyle decisions.

The Study

For this study, rather than looking at individual species, researchers chose to look at Operational Taxonomic Units (OTU's) - i.e. groups of species so closely related (97%+ shared DNA) that we can infer these species to have highly similar functions in the context of the gut. This approach allowed for much more significant correlations in the data compared to looking for similar correlations at the individual species level.

By far he most significant statistical correlation in the data showed that bacteria from the phyla (a higher taxonomic classification) Bacteroides were significantly overrepresented in the guts of depressed patients compared to the non-depressed controls. 

There were other weaker, but still very much statistically significant correlations in the data. Depressed patients consistently had an underrepresentation of bacteria from the family Lachnospiraceae, as well as a slight overrepresentation of bacteria from the families Alistipes and Oscillibacter.

The first diagram below shows all of the 100 OTU's tracked by the researchers, the second diagram their relative levels in the gut. Red OTU #'s are positively correlated with depression, green OTU #'s are negatively correlated with depression.

 

Possible Explanations

The researchers point out a few possible explanations for why these types of bacteria might be correlated with depression. For example, Oscillibacter is known to produce valeric acid as an end product. Valeric acid is a precursor for the neurotransmitter GABA, but it's unclear what the effects are of GABA in the gut, and GABA in the brain is certainly not correlated with depression. So while it's provocative to note that gut flora might be directly interacting with neurochemistry, it seems like a bit of a stretch for explaining these particular correlations. 

It's the second factor that the authors of the article mention (but seem to skirt around for some reason) that jumps out at me as the obvious reason for the correlations: systemic inflammation.

A number of studies in the past few years have examined the connection between inflammation and depression, with some of the researchers even going as far as to declare depression a fundamentally inflammation-driven disease. [7] Looking at the studies on the subject I've seen over the past few years, this seems like perhaps the best explanation for the phenomena of depression we have at this point.

The authors of this study point out that previous studies have shown Bacteroides to be correlated with obesity, another disease in which inflammation plays a significant role. In addition, the genus Alistipes has been directly connected to elevated inflammation levels in a previous study.

I'm hesitant to fully buy-in to the idea that a specific family or genus is in itself pro-inflammatory - the role of a given family or genus can be quite be different from one individual to the next depending on their specific microbiome. That being said, there's no denying the microbiome's role in managing inflammation. 

Certain types of bacteria (Alistipes are one example) will produce pro-inflammatory molecules when exposed to certain conditions in the gut. These conditions almost certainly depend heavily on the relative levels of other bacteria inhabiting a given individual's gut - but the nature of these sorts of ecological-level bacterial interactions in the gut are simply beyond our understanding at this point.

We also know that gut flora play an indispensable role in the health and function of the epithelium, the thin layer of cells that lines your digestive tract responsible for both absorbing your nutrients and keeping undigested food particles out of your bloodstream. 

When the epithelium is compromised, undigested food particles and bacteria can slip into the bloodstream, triggering an inflammatory reaction from the immune system. This condition is referred to as "Leaky Gut Syndrome". In the past few years we've learned that this condition is way more common than we initially thought and might be a primary driver of inflammation for a huge number of people. The prevalence of screwed up gut microbiomes are a big reason why this condition has become so common.

So What To Do?

While it's nice to think we could treat depression by simply culling the levels of Bacteroides and Oscillibacter and adding additional Lachnospiraceae - it is, of course, not quite that simple.

For starters, this is a very early study done on a relatively small sample size. So while the findings are certainly intriguing, it's essentially guaranteed that subsequent studies will bring to light new data that gives this article entirely new context, or even finds it to be inaccurate. That's just how things go in this rapidly expanding field of gastrointestinal microbiology.  

Secondly, we just don't have a good way of getting specific bacterial types to reliably colonize the gut. Probiotic supplements will generally create positive alterations in gut flora, but almost never do the species found in the supplement colonize the gut in a meaningful way.

Finally, even if we had a reliable way to get a certain type of bacteria to colonize the gut, we'd still be ignoring the ecology of the gut that determines how that that type of bacteria will behave after colonization.

Despite these limitations, there's still quite a bit we can do to manipulate our gut microbiome such that inflammation is kept to a minimum.

Thankfully, it's almost always the case that when we simply stop exposing our gut flora to disruptive chemicals (antibiotics, antibacterials, solvents) and start putting in the things that allow bacteria to thrive (dietary fiber, probiotics), the microbiome will grow into a robust, high-functioning state in which immune function and inflammation improve dramatically. 

We don't necessarily understand how or why this balancing happens (yet), but 95% of people will see huge improvements by taking these relatively simple steps.

Nurturing the microbiome is a topic I've written about at length, so I won't delve too deep in to the specific practices I recommend for building a bomb-proof microbiome. For the specifics, I suggest checking out my previous article "An Owners Manual For Your 100 Trillion Gut Bacteria".

Stay Synchro, 

     Graham Ryan

      

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[1] http://www.sciencedirect.com/science/article/pii/S155041311400463X

[2] http://www.biomedcentral.com/content/pdf/1710-1492-10-S1-A63.pdf

[3] http://www.nature.com/cdd/journal/vaop/ncurrent/full/cdd201456a.html

[4] http://link.springer.com/chapter/10.1007/978-1-4939-0897-4_8

[5] http://www.sciencemag.org/content/339/6123/1084.short

[6] http://www.ncbi.nlm.nih.gov/pubmed/24888394

[7] http://www.sciencedirect.com/science/article/pii/S0889159109001135

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