Celiac Disease and Fecal Transplants: When Genes are not Destiny

(So…you might have noticed that I mentioned fecal transplants in last weeks post…only to have nothing ABOUT fecal transplants in the material! Sorry about that brain-fade. Here is the scoop on more poop)

After last weeks exploration of panda poo I really may be down to 6 listeners (or readers in this case) but if you are still with me you clearly have a strong constitution or a borderline unhealthy fascination with scat. No judgements on my part, just an observation. This week I want to look at an interesting condition (Celiac Disease) and consider it from the perspective of the Discordance Theory while also investigating it as an example of how tweaking our epigenetics (in this case gut microbiome) can potentially turn a disease process on or off.

Celiac Disease is an autoimmune condition that has historically been linked to folks of Northern European ancestry, however recent research suggests just about any ethnic group http://ift.tt/2lpNGIe may be affected by the condition. The quick and dirty story on CD is that a protein (gliadin) in certain grains (wheat, rye, oats, barley, millet) can cause intestinal permeability and precipitate an autoimmune response to the gut lining (and beyond). Celiac complications can affect ANY organ, system or tissue as part of the disease process is the formation of a hapten http://ift.tt/2mss96u between the gliadin protein and a ubiquitous enzyme called tissue transglutaminase (TTG). TTG is active in just about every cell imaginable, so if the body mounts an immune response to TTG, it can affect anything from the brain to the heart to the much more commonly understood, gut lining. This very ubiquity of affected tissues and organs makes diagnosis of celiac challenging as not everyone presents with GI problems. It is this fact however that has made me reasonably successful in working with folks as I tend to hold any gluten consumption as suspect. So I tend to recommend full avoidance of gluten for 30 days, followed by a reintroduction and assessment of general wellbeing both with and without gluten containing foods. This is a simple, safe, TRANSPARENT process that has helped a lot of people but you would not believe the hand-wringing and belly-aching about suggesting that we ditch bread and eat more yams and fruit for a month.

I’m sure most of you are reasonably familiar with CD but I wanted to provide a bit of background for the folks who may be new to the site. Something that is likely new to most of you is looking at CD not for its disease process, but what benefits the genetic predilection for CD may bring to the affected individual. Some of my most fruitful research has come about from searching a certain condition in the following way: “celiac disease EVOLUTIONARY ADVANTAGE.” It’s interesting to do this process with things like Huntington disease and even BRCA (the “breast cancer” genes). I encourage you to do a bit of exploring along this line and let folks know what you find in the comments.

Many people look at CD as a “weakness” but this is not only an oversimplification, it’s just inaccurate. Folks with the genetic predisposition for CD appear to have an enhanced immune response, particularly in relation to gut pathogens. In a pre-antibiotic era, particularly one in which people were making the transition to living in cities, or on farms in close proximity to domesticated animals, having a robust immune response to gut pathogens was clearly a net win. Unfortunately for the CD carrier, this enhanced reactivity can be hijacked by the anti-predation chemicals used by things like gluten containing grains and this ultimately manifests in what we commonly describe as celiac disease. This is the simple biological tradeoff we see throughout nature and it makes the point that an “advantage” or “disadvantage” is situationally specific. Given easy access to antibiotics and the difficulty in avoiding gluten in our modern, highly processed, “manufactured on shared equipment” world, celiac disease may not be much of an advantage these days. I know it’s not a party for me! There is another interesting wrinkle to the CD story which is that throughout most of history, CD was diagnosed due to severe wasting and malabsorption. Affected individuals were effectively starving to death as their gut lining was so damaged they absorbed little of what they consumed. Sine the 1980’s however, CD has become more and more associated with not wasting, but obesity. The reasons for this shift are unclear but it may have to do with a shift in gut flora. File that nugget away for a moment as we consider that not everyone who develops CD has the “genetic predisposition.” There are some case reports (not a lot to go on but interesting) that certain infections, Giardia for example, can precipitate celiac disease.  What’s interesting in these cases is individuals had no CD symptoms before giardia infection, after clearing the giardia (using some pretty robust antimicrobials) some folks see a complete healing of the gut, while others continue to manifest CD pathology. I happen to be in that latter category.

Remember I asked you to file away that nugget about changing gut microbiome and CD? Ok, here is where we pull that out. There is preliminary research suggesting that some folks with CD may be able to completely reverse the condition with a fecal transplant. One might make the pithy observation “The microbes giveth, and the microbes taketh away.”

Now, what might be happening in the case of the fecal transplant mitigating or reversing celiac disease? It’s possible the transplanted microbiota reduce inflammation in such a way that the intestinal permeability which leads to an autoimmune response just does not happen. In a related although peripheral mechanism, these “new” bacteria might have the enzymes to properly degrade gliadin, making it a non-issue for the CD prone individual. This should be reminiscent of my last post talking about the panda microbiome potentially shifting in such a way to make cellulose (bamboo) a viable food source.

This is all potentially interesting stuff if you are really into poo, but what are some takeaways?

1-From a biological perspective any given set of traits could be a boom or a bust. This is a highly situationally specific story. A frisky immune response may decrease the likelihood of succumbing to infectious disease, but this might also increase our likelihood of autoimmune disease, including atherosclerosis.

2-Despite “genetic predisposition” one may or may not develop a given condition, and this seems to be driven by factors such as sleep, food, stress and of course, the gut microbiome. Genes are as much potential as destiny.

3-Although it is clear that the gut microbiome will be a treasure trove of medical insights, we are far, far away from any type of pin-point diagnostic and predictive processes. Right now the best that I see happening is we find folks who are “healthy” make a poo-milkshake from their morning offerings, then turkey-baster that up the backside of someone who is “not healthy.” We are looking more and more at the various strains of bacteria, trying to find the “good” ones, but my prediction on that is it will largely be a failure as a legit diagnostic/implementation tool. If you recall from the last blog post on panda digestions, pandas still exhibit the gut microbiome of a carnivore, yet are clearly using the cellulose found in bamboo to fuel their existence. The likely, although as to yet be established story, is those “carnivore” microbes have taken on the genes necessary to degrade and ferment cellulose. So, we MIGHT find some magic strains of bacteria, but I’d not be surprised if we start not looking for bacterial strains, but specific bacterial genes or gene families which confer a desired metabolic effect.

4-Given the complexities of point #3, and although it’s important to dig into those complexities, we need to also keep an eye on outcome based approaches. We may not know exactly what worked, but so long as people are getting favorable results, so long as that process is being conducted in a rigorous way, we do not need to understand the exact “why’s” to be able to give folks better options than they have now.

I talk about all of these nuances and a good bit more in my forthcoming book, Wired To Eat. I think it’s important to understand there IS a process that will help you look, feel and perform better. That process is likely different than what will work for your neighbor, co-worker or spouse, and none of those individual processes are any more (or less) valid than the others. What is important is you have the will to tinker and a framework to objectively test and find your way to optimal health.

from The Paleo Diet http://ift.tt/2lbHSqA