The Macrobiome and the Microbiome: A Dynamic Duo

I stumbled across an article[i] yesterday morning on the gut-brain axis in autism, and its relationship to the gut microbiota.  It is an interesting review of our current scientific knowledge on this subject.  What jumped out at me most is the authors’ summation of potential therapeutics for autism spectrum disorders, targeting the microbiota-gut-brain axis:  probiotics, helminths and diet.

I could not agree more!

What is odd is that in their discussion of probiotics and diet, their therapeutic effect on the microbiota is made clear.  However, while the authors suggest that using helminths is anti-inflammatory and has beneficial effects on mucosal barrier function, at no point do they mention helminths’ direct therapeutic effect on the microbiota.

This inspired me to write a little about this topic.

It makes perfect sense, of course, that the macrobiome would affect the microbiome (and vice versa…but I’ll save that for another day).  After all, they evolved simultaneously.  It seems only logical that, like good neighbors, they’d work together to keep their co-inhabited real estate in good order.

Still, it’s a very new area of research apparently, as the first mention I can find in the literature only dates back until 2010.  Walk et. al.[ii] noted a “significant shift” in the composition of intestinal bacteria in helminth-colonized rodents, toward anti-inflammatory species.

Two other great articles on the topic:

In 2015, McKenney et. al[iii]. compared the microbiota of rats colonized with the helminth, Hymenolepis diminuta (HD), which is a generally benign helminth, native to rodents. The colonized rats had, “…profound changes in the microbiota in response to enriching the gut ecosystem with a helminth,” when compared to the controls.  What is really interesting is that the shift is away from inflammatory bacteria associated with a “Western diet” (high in fats and sugar), toward anti-inflammatory species of Clostridia “…that are known to tighten the epithelial barrier and decrease propensity for allergy.”

In 2016, researchers at New York University demonstrated again that the presence of helminths leads to markedly higher levels of anti-inflammatory bacteria, and lower levels of pro-inflammatory bacteria.  These researchers demonstrated that this phenomenon holds true across multiple species of both helminth and host, including humans.[iv]  (I mention this one as my #1 favorite scientific study of 2016 in my Top 10 blog post!)

One of the first groups of researchers looking into this subject were University of Manchester scientists, led by Ian Roberts and Richard Grencis.[v] In a description of their work, posted on the University’s website[vi], Professor Roberts summarizes their work:  “It is like a three-legged stool – the microbes, worms and immune system regulate each other.”

And that really IS the best possible image to explain this concept.  Each of these “legs” is reliant upon the other to keep the organism healthy and stable.

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[1]Li, Q, Zhou, JM. The microbiota-gut-brain axis and its potential therapeutic role in autism spectrum disorders. Neuroscience. 2016;324:131-139.

[ii] Walk, ST, Blum, AM, Ewing, SA, Weinstock, JV, Young, VB. Alteration of the murine gut microbiota during infection with the parasitic helminth Heligmosomoides polygyrus. Inflammatory Bowel Disease. 2010 16(11):1841-9.

[iii] McKenney, EA, Williamson, L, Yoder, AD, Rawls, JF, Bilbo, SD, Parker, W. Alteration of the rat cecal microbiome during colonization with the helminth Hymenolepis diminuta. Gut Microbes. 2015Apr;6(3):182–93.

[iv] Ramanan, D,  Bowcutt, R,  Lee, SC, Tang, MS,  DK, Zachary, Ding, Y, Honda, K, Gause, WC, Blaser, MJ, Bonneau, RA, AL Lim, Y,  Loke, P, Cadwell, K. Helminth infection promotes colonization resistance via type 2 immunity. Science. 2016;352(6285):608–12.

[v] Haves, KS, Bancroft, AJ, Goldrick, M, Porsmouth, C, Roberts, IS, Grencis, RK. Exploitation of the intestinal microflora by the parasitic nematode Trichuris muris.  Science. 2010;328(5984):1391-4.

[vi] Retrieved on 2/7/17 from:  http://www.manchester.ac.uk/discover/news/how-the-parasitic-worm-has-turned