A Treatment for Leaky Gut Around a Corner or Two???

Last week, I posted a story on the Biome Buzz’ Facebook page about how a metabolite from pomegranates and berries has been found to reduce inflammatory bowel disease.[i]  Researchers at the University of Louisville discovered that the metabolite,  urolithin A (UroA) and a synthetic form they have devised, increases the proteins that tighten the junctions at the epithelial border, stopping leaky gut.  This, in turn, keeps toxins, undigested food, bacterial metabolites, etc. from getting into the blood stream and causing a major systemic inflammatory response.  As of now, there are no pharmaceutical treatments for leaky gut, so this is potentially a huge step forward.

“In pre-clinical studies conducted by the researchers, oral administration of either UroA or its potent version synthetic analog has clearly shown the beneficial effect in reducing the colonic inflammation, in acute and chronic colitis. A series of in vitro and in vivo experiments revealed that these small molecules reduce gut permeability by restoring the epithelial barrier by overexpressing the junctional proteins.”

It is really a very exciting finding, especially as UroA has been shown to not only treat existing colitis but also, to prophylactic in preventing it in the first place.  Giving the metabolite to mice who have fully developed IBD has reversed the disease; but also, giving the mice UroA and then provoking gut inflammation with chemicals that cause colitis prevented the mice from developing IBD.

This story gets even more interesting in that, it is the gut bacterium, Bifidobacterium pseudocatenulatum that is responsible for generating UroA from these fruit.  Thus, some people produce less UroA from their diets because they have lower levels of this bacterium.  In fact, some people may not have it at all! Says the lead researcher, “Our study shows that direct consumption of urolithin A or its analog can compensate for a lack of the specific bacteria responsible for production of urolithin A and continuous consumption of pomegranates and berries.”[ii]

Unfortunately, there are no commercial probiotics that can as yet rectify the depletion of Bifidobacterium pseudocatenulatum.  A 2016 article though states that a new company, Amazentis, has created a urolithin A product and started clinical trials.[iii]  In 2017, the company issued a press release stating that their product successfully passed through phase 1A/1B double-blind, randomized, placebo-controlled trials in elderly people.  Why, you ask, did they test the product first in the elderly?  Because, as it turns out, UroA is not only effective in tightening the gut epithelium.  It also improves the functioning of mitochondria, the powerhouse of every cell in the body.[iv]  We all recycle  mitochondria in a process called mitophagy.  As we age though, this process does not work efficiently: “If worn-out mitochondria are not recycled, they and their decomposing components build up inside cells, eventually causing problems in many tissues, including muscle, which gradually becomes weaker.”  There is evidence, that this build-up of faulty mitochondria may play a role in the loss of muscle and subsequent frailty in the elderly and too, may be somewhat responsible for the development of Parkinson’s and other diseases associated with aging.

UroA is, thus far, the only known molecule that can restore normal mitophagy.  In their initial experiment, done on the worm C.elegans, scientists found the organisms lived, on average, 45% longer when given UroA.  Experiments on rodents showed similar results, and this then lead to this first human trial.

 So…at this point, this is a waiting game for all of us.  We have no way that I have found yet of increasing levels of Bifidobacterium pseudocatenulatum, and, many of us may have lost the species altogether.  I’ll follow this research, obviously.  Considering the health implications for so many of us, I hope it won’t be too long before Amazentis’ product becomes available or, a perhaps a probiotic to replace what we have lost.

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[i] https://www.eurekalert.org/pub_releases/2019-01/ncfb-mfp010919.php?fbclid=IwAR2vANUmOx5DNAs0GetbdC98Qhpg0Ai5IVbb_rzbTGT0rQDku0W0ey9Ext

[ii] http://www.sci-news.com/medicine/urolithin-a-inflammatory-bowel-diseases-06807.html

[iii] https://www.medicalnewstoday.com/articles/311572.php

[iv] https://www.medicalnewstoday.com/articles/311572.php