• E. coli bacteria exploits Crohn's diseas

    From ScienceDaily@1:317/3 to All on Wed Apr 27 22:30:48 2022
    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

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