Tuesday, March 19, 2019

More on molybdenum and diarrhea

An older gentleman I know recently decided to try molybdenum glycinate to alleviate his recurring diarrhea, and it helped him. That brings the number of people to three--of whom I know--who have found molybdenum relieves their (non-viral-gastroenteritis-associated) diarrhea. How does it do it? The most plausible mechanism I've come across is molybdenum's role--as part of a cofactor needed by enzymes mARC-1, mARC-2, xanthine oxidase, and aldehyde oxidase--in converting nitrite into nitric oxide, which nitric oxide then inhibits an "on-switch" (adenylyl cyclase) of secretory diarrhea. (Links to supporting studies are in this earlier post.)

But some people report that molybdenum supplementation causes diarrhea in them. (See https://forums.phoenixrising.me/threads/who-has-experienced-an-adverse-reaction-to-molybdenum.21686/) I think the best explanation for that happening is individual variations in gut bacteria. For example, a study last year found that depriving a certain category of gut bacteria of molybdenum resulted in reduced colitis-associated inflammation.

 In a provocative study recently published by Zhu et al., the authors demonstrated how precision editing of the gut microbiota may be used as a treatment for gastrointestinal inflammatory disease []. The authors had previously identified Enterobacteriaceae family expansion and overrepresentation of molybdenum-cofactor-dependent metabolic pathways in a model of chemically induced colitis. Molybdenum-cofactor-dependent pathways are essential for the overgrowth of Enterobacteriaceae in the inflamed gut [], and Zhu et al. demonstrated the targeted inhibition of these pathways by oral administration of tungstate, as tungsten can replace molybdenum in the molybdopterin cofactor. The resulting restriction of Enterobacteriaceae growth restored the microbial diversity to a normal state. Furthermore, colitis-associated inflammation was reduced in the tungstate-treated animals by up to 90%.
In the next step toward translating this treatment to humans, the authors took gut microbiota from a subset of patients with inflammatory bowel disease (IBD) and transferred these communities into germ-free mice. When inducing colitis, animals receiving tungstate showed decreased Enterobacteriaceae expansion and associated markers of inflammation, thereby demonstrating that this treatment, or other means of inhibiting molybdenum-cofactor-dependent pathways in bacteria, may be an effective means of controlling inflammation in patients with IBD []. 

- Extract from Petrosino "The microbiome in precision medicine: the way forward" Genome Med (2018) 10:12 (online at https://link.springer.com/article/10.1186/s13073-018-0525-6), which summarized the findings of Zhu, Wenhan et al. "Precision editing of the gut microbiota ameliorates colitis" Nature (2018) 553(7687):208-211 (online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5804340/).

What the above means is that someone suffering from colitis (inflammation of the colon), a symptom of which can be diarrhea (see https://www.medicinenet.com/colitis/article.htm), could be better off avoiding molybdenum supplements if they have too many inflammation-associated Enterobacteriaceae in their gut.

Molybdenum is not a panacea. It's shown itself awesome for many ills--namely, gastroenteritis (especially viral), migraines, and secretory diarrhea--and it deserves far more attention than it currently gets. But like everything else that can affect our bodies and the bacteria within us, it needs to be used wisely.

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