E. coli bacteria exploits Crohn's disease inflammation
Date:
April 27, 2022
Source:
Cornell University
Summary:
A multi-year study of the role of E. coli gut bacteria in Crohn's
disease finds that intestinal inflammation liberates chemicals
that nourish the bacteria's growth and promotes their ability to
cause inflammation.
FULL STORY ==========================================================================
A multi-year study of the role of E. coligut bacteria in Crohn's disease
finds that intestinal inflammation liberates chemicals that nourish the bacteria's growth and promotes their ability to cause inflammation.
==========================================================================
The results identify new avenues for treatments that selectively disrupt
the compounds that feed E. coli.
The study, "Mucosal Metabolites Fuel the Growth and Virulence of E. coli
Linked to Crohn's Disease," published April 12 in the journal JCI Insight, focuses on ileal Crohn's disease, an inflammatory bowel disease that
affects the last part of the small intestine.
A particular type of E. coli, called adherent and invasive E.coli
(AIEC), which stick to and invade cultured epithelial cells from the
intestine (the gut lining) and replicate in defensive white blood cells (macrophages), has been isolated in 21 to 63% of patients with ileal
Crohn's disease, leading researchers to suspect AIEC plays a key role
in the disease process.
The researchers adopted a patient-based multidisciplinary approach to
identify factors found in patients associated with ileal AIEC, and the
impact of these factors on growth and virulence of AIEC. Dr. Shiying
Zhang, a senior research associate in the College of Veterinary Medicine, spearheaded the experiments related to AIEC, guided by the multi-pronged analyses of Dr. Xochitl Morgan at the University of Otago.
"This study gives us a whole new patient-based roadmap of things we
might want to target to stop Crohn's associated E.coli from growing and inciting inflammation," said senior author Kenneth Simpson, professor
in the Department of Clinical Sciences in the College of Veterinary
Medicine and at Weill Cornell Medicine in New York City.
========================================================================== Genetic defects, diet and gut bacteria are all suspected to play roles in Crohn's disease. Studies have shown that inflammation and the composition
of the microbiome (gut bacteria populations) are interlinked, such that
when the gut is inflamed, the microbiome switches from more beneficial
bacteria to more unfriendly bacteria, such as E. coli.
In this study, the research team characterized the ileal microbiome,
chemical environment and cultivable bacteria along with the genetic predisposition of patients with and without Crohn's disease. They wanted
to answer why intestinal inflammation drives a shift towards E.coli
across people, dogs, cats and mice.
"Our thought was that this type of E.coli may use substances generated
by intestinal inflammation to grow and outcompete other bacteria,"
Simpson said.
"Essentially we found that the ileal mucosa provides an extensive menu
of chemicals that AIEC can mix and match for growth and virulence." The researchers determined that inflammation creates a chemical environment
that is enriched in a number of compounds (called metabolites),
notably phospholipids and amino acids, that Crohn's associated E.coli
can selectively use for growth, energy, stress resistance and movement
towards the gut lining.
They next determined that phospholipid associated ethanolamine, and
glutamine, accentuated the aggressive behavior of AIEC in cultured cells,
and they linked use of ethanolamine to intestinal inflammation in a
model of inflammatory bowel disease.
Previous studies have identified that people with ileal Crohn's disease
have defects in genes that impair the ability of macrophages to kill
AIEC. This study links E.coli survival in the gut to their ability to
replicate in macrophages. "Adherent Invasive E. coli is really hardy
and its ability to survive in the inflamed gut, where other bacteria
perish, may also enable it to thrive within the macrophages of a Crohn's susceptible individual, " Simpson said.
The team found that E. coli in many people with Crohn's are resistant
to multiple classes of antibiotics. They believe that indiscriminate
use of antibiotics may promote gut E. coli and related bacteria that
can then exploit a susceptible individual.
Co-authors include researchers from the Jill Roberts Center for
Inflammatory Bowel Disease; the Boyce Thompson Institute; and the
Center for Gastrointestinal Biology and Disease at the University of
North Carolina Chapel Hill; University of Otago in New Zealand; Harvard University; Shimane University in Japan; and the John Radcliffe Hospital
in the United Kingdom, among others.
The study was funded by the Crohn's Colitis Foundation, Helmsley Trust,
the National Institutes of Health, and the late Jill Roberts, who inspired cross- campus research at Cornell, and founded the Jill Roberts Center
and Institute for Inflammatory Bowel Disease.
========================================================================== Story Source: Materials provided by Cornell_University. Original written
by Krishna Ramanujan. Note: Content may be edited for style and length.
========================================================================== Journal Reference:
1. 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 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/04/220427115747.htm
--- up 8 weeks, 2 days, 10 hours, 51 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)