The Bacterial Microbiota in Mental Illness: A Shifting Paradigm?

So many studies have come out recently that are of interest that I had a hard time choosing the winner for today’s post.  I finally settled on an article[i] from the journal, Medical Sciences, on the potential use of microbiome manipulation in treating neuropsychiatric disorders, as so many of us, friends and family, are now affected by “mental” illnesses ranging from depression to anxiety disorders to autism.

There was so much in this paper that it’s an almost overwhelming task to select the highlights for this post.  I’ll do my best!

First though, I have to tell you what stunned me right off the bat.  Did you know that the first paper ever published (in the British Journal of Psychiatry) on the use of “psychobiotics” (probiotic bacteria that have a beneficial effect on psychiatric illness) dates back to 1910?!  That is astounding! Over 100 years ago, scientists already recognized the potential, and tested the efficacy, of Lactobacilli in treating depression:  “Melancholia…lends itself at once to a dietetic form of treatment.”[ii]

We haven’t made a hell of a lot of progress in the last 109 years, have we?

Ok – back to highlights:

1. I know you already know this but to emphasize a crucially important point:  we know that the gut-brain axis is bi-directional. For example, “Chronic stress reduces the proportion of Bacteroides and increases the proportion of Clostridium species in the host microbiome” while, conversely, “Use of antibiotics before the age of one correlates with adulthood depression.” Changes in behavior alter the microbiota.  Changes in the microbiota alter behavior.

 

2. There’s a particularly interesting section on leaky gut, with the authors providing numerous references to the medical literature from some of the most eminent journals in medicine including Nature and Gut. “This effective barrier can be impaired for various reasons (e.g., stress, exogenous glucocorticoids, dysbiosis, and endotoxins) and a ‘leaky gut’ may result…Psychobiotics reduce the severity of symptoms associated with a leaky gut and neuroinflammation. For example, Bacteroides fragilis can repair bowel leakage and reduce endotoxin-induced autistic behavior.”  I had never read that about B.fragilis.  Might be worth adding some to your regime if you suspect leaky gut???

 

3. In terms of probiotics known to boost levels of regulatory cytokines (which modulate our inflammatory response), the article specifically mentions Lactobacillus GG and Bifidobacterium infantis, both of what have also been shown to improve the permeability of the blood-brain barrier.

 

4. Various strains of probiotic bacteria are known to produce specific neurotransmittors. For example, Enterococcus and Streptococcus produce serotonin, while Bacillus produces dopamine and noradrenaline.  Bifidobacteria and Lactobacillus produce the inhibitory neurotransmitter, GABA.

 

5. The article provides a general summary of some of the clinical trials, both animal and human, that have shown promising results. For example, in an animal study, Lactobacillus helveticus and Bifidobacterium longum both reduced anxiety scores, and this was actually replicated in healthy humans.  Many of the studies mentioned, you’ve already read about on the Biome Buzz, in posts like this one.   The authors do mention one “seminal” study wherein, using fecal microbiota transplant (FMT), germ-free mice were given either microbiota from depressed humans or healthy humans.  In the former group, the mice were “…found to have a pattern of behavior consistent with depression…”  The results of this study have been replicated.  (I’m waiting for the first human FMT study in depression.  See below!!!)

 

6. I was somewhat aware that psychotropic drugs had physiological effects beyond what they do in the brain, but was shocked at the extent: “Psychotropic drugs used in the treatment of neuropsychiatric disorders may alter the composition of the microbiota.  Most psychotropic drugs show antibiotic activity…The positive effects of psychobiotics can be negated when they are administered to patients receiving psychotropic agents.”  Some specific examples:  “The potent antipsychotic chlorpromazine [Thorazine] has antibiotic/antifungal activity.  Monoamine oxidase inhibitors [MAO inhibitors] produce an antimicrobial effect by inhibiting cell wall synthesis, selective serotonin reuptake inhibitors (SSRIs) by inhibiting the efflux pump…” etc.  The authors conclude this section by stating:  “In addition to their synaptic effects, currently prescribed psychotropics may also contribute to a therapeutic effect by altering the composition of the microbiota.”

In their conclusion the authors state that we are undergoing a “significant paradigm shift” in the treatment of neuropsychiatric disorders.

Well, of course, the Biome Buzz is on top of every biome news story and following this paradigm shift closely, but on occasion, my timing even astounded me.  This morning, the biome headlines are screaming about a new, large scale study looking at microbiota differences between those with and without depression.  Uncanny coincidence, right?!  Microbiologists in Belgium analyzed the microbiota of 1074 Belgians, 173 of which were diagnosed with depression, and found:

“Two kinds of microbes, Coprococcus and Dialister, were missing from the microbiomes of the depressed subjects, but not from those with a high quality of life. The finding held up when the researchers allowed for factors such as age, sex, or antidepressant use, all of which influence the microbiome…They also found the depressed people had an increase in bacteria implicated in Crohn disease, suggesting inflammation may be at fault.”[iii]

Because microbiota vary from population to population, they also looked at a population of 1064 Dutch people and found those exact same two species missing in the those with depression.

They then tried to figure out what it is about these species that could be causative of depression and compiled a list of 56 substances that gut bacteria produce or breakdown which could affect the nervous system.  They found, for example, “…that Coprococcus seems to have a pathway related to dopamine, a key brain signal involved in depression, although they have no evidence how this might protect against depression. The same microbe also makes an anti-inflammatory substance called butyrate, and increased inflammation is implicated in depression.”

While this is not yet proof that the missing species are the cause of the depression, this is still a major step forward toward creating a psychobiotic to treat the illness.  And by the way, according to this article from Science Magazine, a clinical trial using fecal microbiota transplant to treat depression is planned at the University of Basel in Switzerland!  I have high hopes.

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[i] Evrensel, A, Onen Unsalver, B, Ceylan, ME. Therapeutic potential of the microbiome in the treatment of neuropsychiatric disorders.  Medical Sciences. 2019:7, 21.

[ii] Phillips, J. The treatment of melancholia by the lactic acid bacillus. J. Mental. Sci. 1910, 56, 422–430.

[iii] https://www.sciencemag.org/news/2019/02/evidence-mounts-gut-bacteria-can-influence-mood-prevent-depression?r3f_986=https://www.google.com/