How Gut Inflammation Feeds Pathogenic Bacteria in Crohn’s Disease

The results of a multi-year study of the role E. coli plays in Crohn’s Disease is absolutely fascinating.  Back in December, 2021, I described to you research that showed that stress can cause flare-ups of Crohn’s by leading to an increase in invasive E.coli (“adherent-invasive E.coli (AIEC for short)).  Stress hormones decrease those very immune cells that kill off pathogens.  This invasive E.coli has been found in up to 63% of people with Crohn’s.

In a continuing effort to understand exactly why the microbiome changes and how this leads to the intestinal inflammation seen in inflammatory bowel disease, scientists characterized the small intestine microbiome, as well as the chemical environment and genetic predispositions of patients with and without Crohn’s.[i]  This same pattern of a drive toward AIEC is seen in not just humans, but dogs, cats and mice as well.  The scientists theorized then that AIEC may feed on substances produced by intestinal inflammation, giving them a competitive advantage over other, beneficial, species.

It turns out that their hypothesis was proven correct: they found that the ileal (part of the small intestine) mucosa provides an “extensive menu of chemicals” that promote the growth and virulence of AIEC.  These metabolites include phospholipids and amino acids that AIEC  can “…selectively use for growth, energy, stress resistance and movement toward the gut lining.”[ii]  More than that, they were able to determine that a metabolite called ethanolamine, as well as the amino acid glutamine, increase the aggressiveness of AIEC. The authors write that in an in vitro model, “We link metabolism to virulence, finding that ethanolamine and glutamine enhance AIEC motility, infectivity and pro-inflammatory responses…”

To make matters worse, the AIEC found in people with Crohn’s tends to be resistant to multiple kinds of antibiotics.  Thus, the use of antibiotics does nothing except promote the growth of AIEC as its competition gets killed off.  Thus, there is no suggestions yet as to how to best treat this.  Stress reduction?  Diet?  Let us hope that some kind of treatment will be found in the not-very-distant future.

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[i] Shiying Zhang, Xochitl C, Morgan, Belgin Dogan, Francois-Pierre Martin, Susan R. Strickler, Akihiko Oka, Jeremy Herzog, Bo Liu, Scot E. Dowd, Curtis Huttenhower, Matthieu Pichaud, Esra I. Dogan, Jack Satsangi, Randy Longman, Rhonda Yantiss, Lukas A. Mueller, Ellen Scherl, R. Balfour Sartor, Kenneth W. Simpson. Mucosal metabolites fuel the growth and virulence of E. coli linked to Crohn’s disease. JCI Insight, 2022; DOI: 10.1172/jci.insight.157013

[ii] https://www.sciencedaily.com/releases/2022/04/220427115747.htm

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