The Mighty Microbiome!

 The Mighty Microbiome!

I am using a recently published review article for this edition of Extra Credit. A review article is essentially a summation of a collection of research studies from which the authors are interested in compiling data. Depending on how many studies the authors choose to compile, a review article can be fairly lengthy (and this one is!). This particular article can be a bit deep when wading through the physiology, but the implications of the research being presented are weighty!

The authors highlight the profound impact that the microbiome has at every stage of life on neurodevelopment and cognition and disease.

Citation:  Sharon G, Sampson T, Geschwind D, Mazmanian S. The Central Nervous System and the Gut Microbiome. Cell [serial online]. November 3, 2016;167(4):915-932. Available from: MEDLINE Complete, Ipswich, MA. Accessed November 12, 2016.

Click here for the full text of the review article.

Fetal Development

There were many animal studies that were reviewed within this paper and some of the most compelling involved germ-free (GF) mice (these are mice that have no microbes in their guts, by design).

There are immune cells in the brain and spinal cord, called microglia. The microglial cells from GF mice were very limited in their response to virus and bacterial infections. However, researchers could ‘correct’ the responses by administering short-chain fatty acids. This is interesting because one of the benefits conferred upon humans by gut microbes is the production of short-chain fatty acids (SCFA’s). When these become imbalanced or too few in concentration, we can manifest certain diseases.

The blood brain barrier (BBB) is of great structural importance to the body. It is an extremely selective barrier between the brain and the rest of the body. Similar in function to the lining of the gut. In fact, the integrity of both the gut lining and the BBB are maintained by ‘tight junction proteins’. This is why a lot of times when we see permeable guts, conditions are also right for a permeable blood brain barrier. Researchers found that in GF mice, the BBB was more permeable. Furthermore, they could reverse this permeability by administering butyrate (a short-chain fatty acid produced by gut bacteria).

Another study looked at administration of antibiotics during pregnancy, as we have known for some time that antibiotic use in pregnant mothers adversely affects offspring health and immune status. When antibiotics were administered to gestating mice, the offspring’s gut microbiome was considerably different than their non-medicated counterparts. As well, the medicated offspring also exhibited lethargy, anxiety-behavior and movement deficits.

Diet was also found to be a critical component during pregnancy. In rat studies, poor diets led to offspring that were less social and exhibited repetitive behavior tendencies. The lack of social behavior could by reversed by administering Lactobacillus reuteri (this is a strain of bacteria that was found to be missing in the offspring’s microbiota).

Large, epidemiological studies have found that infections during pregnancy significantly increase the risk that the offspring will develop schizophrenia and to a lesser extent, the data correlates to a higher incidence of autism spectrum disorder.

On-Going Brain Development in Adults

We know that certain cells in the brain (primarily glia) continue to proliferate throughout life and it appears that tinkering with the microbiome can positively or negatively affect cognitive function, myelination and neurogenesis!

  • In adult mice, giving long-term antibiotics led to decreased neurogenesis and ultimately the mice developed an inability to recognize objects. Researchers were able to remedy these deficits with exercise and probiotic administration.
  • Neurogenesis (the production of new brain cells) in adults can be induced by serotonin. And 90% of the body’s serotonin is produced in the gut! There was a study that looked at serotonin production in germ-free (GF) mice and it was determined that they made 60% less serotonin from their guts than did mice with a normal microbiome (Yano, J.M., et al, 2015) .

While more research needs to be done, it appears that there is an inextricable linkage between the microbiome and both pre- and post-natal brain development and on-going neurogenesis.

In Summary…

Since I have most likely lost half of my readers at this point…I’ll just wrap this up with a few, hasty notes from the balance of this incredible review article:

  • Depression, anxiety, autism and schizophrenia all have research linking either assaults on the microbiome (through food or medication) or decreased microbial diversity (not having very many, unique strains occupying the gut) to these neurological conditions.
  • Neurodegenerative disease like Parkinson’s and Alzheimer’s also have some studies linking them to neuroinflammation, which is a process mediated by the brain’s immune system. And we know that gut bacteria and some of their by-products of metabolism (namely short-chain fatty acids) induce proper functioning of the brain’s immune system. So we can surmise that the microbiome has a role to play in the development of neurodegenerative disease!

There is so much more than I could possibly comment on or distill in this Extra Credit edition, but suffice it to say, there is some very exciting research going on as we seek to understand the complex relationship between we humans and the little microbes we host. I strongly suggest that you access this article and give it a read!

Yano, J. M., et al. (2015) Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis. Cell, 161 (2). pp. 264-276. ISSN 0092-8674.