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        Bacteria underlie success of

        fecal microbiota transplants

             he effectiveness of fecal       colitis, the most common form       engagement. In further experiments
             microbiota transplantation      of inflammatory bowel disease,      with mice, the Odoribacter strain
        T(FMT) in treating ulcerative        which affects more than 2 million   had a strong protective effect
        colitis depends on a small set of    people worldwide.                   against colitis.
        beneficial bacterial strains, suggests
        a new study from researchers         FMT as a treatment for colitis      This protective effect was
        at Weill Cornell Medicine and        is based on the idea that colitis   associated with three
        NewYork-Presbyterian.                patients have largely lost the      interconnected mechanisms:
                                             bacteria that normally help         an increase in the level of anti-
        In the study, reported in            maintain gut health by restraining   inflammatory immune cells, an
        Gastroenterology, the researchers    gut inflammation. However, despite   increase in levels of the anti-
        sampled gut bacteria from healthy    FMT’s striking successes in         inflammatory signaling protein
        FMT donors and from FMT              some patients, it is a somewhat     IL-10, and an increase in levels
        recipients with ulcerative colitis,   crude approach that requires the   of short-chain fatty acids such
        identifying the bacterial strains    securing of donor material, and     as butyrate that have been
        whose transfer correlates with       brings a risk of infection, including   previously linked to gut health
        treatment effectiveness.             with emerging pathogens.            and protection from colitis.
                                             Moreover, its effectiveness is well
        The scientists found that one of     below 100% and seems to depend      “These three mechanisms
        these strains was linked particularly   on the FMT donor.                didn’t completely account for
        strongly to treatment success.                                           Odoribacter’s effects, so there are
        They showed that its protection      In principle, though, researchers   still some mechanisms that remain
        against colitis involves several     could overcome these drawbacks      undiscovered,” said Longman,
        interrelated mechanisms, including   by discovering the factors that     who is also an associate professor
        the induction of an increase in anti-  make FMT work and finding ways to   of medicine in the Division of
        inflammatory T cells in the gut, and   deliver just those factors to patients,   Gastroenterology and Hepatology at
        the production of anti-inflammatory,   conceivably even in pill form.    Weill Cornell Medicine.
        gut health-promoting molecules
        called short-chain fatty acids.      In the study, the researchers       The results suggest, in any case,
                                             analyzed samples from 20            that FMT might eventually be
        “Fecal microbiota transplant has     ulcerative colitis patients, before   replaced with a more refined and
        been shown to be effective in        and after FMT, and samples          efficient technique, for example
        several clinical trials, but ultimately   from the FMT donors. Using     based on the transfer of one or
        we need to identify the specific     advanced bacterial strain-tracking   more specific bacterial strains.
        microbial factors that make it work   techniques, they identified
        and focus on delivering those,”      twelve strains whose successful     Longman and his research team
        said senior author Dr. Randy         transfer was linked to treatment    currently are running a clinical
        Longman, director of the Jill        success – and indeed predicted      trial of FMT to determine, in part,
        Roberts Center for Inflammatory      success with high accuracy in an    whether the addition of dietary fiber
        Bowel Disease at Weill Cornell       additional set of FMT-receiving     improves the ability of Odoribacter
        Medicine and NewYork-                ulcerative colitis patients.        or other beneficial bacterial strains
        Presbyterian/Weill Cornell Medical                                       to treat colitis.
        Center. “This study takes us a       The researchers reasoned that
        significant step closer to that goal.”  bacterial strains engaging the   “Our hope is that we can find a way
                                             immune system would be most         not just to transfer these beneficial
        Scientists over the past two         likely to contribute to treatment   microbes successfully but also to
        decades have begun to recognize      effectiveness. Using an advanced    boost their beneficial activities in
        the broad importance of gut-         technique called IgA-seq, they      recipients,” said first author Svetlana
        resident bacteria in regulating      found that only one of the          Lima, a postdoctoral research
        human health, especially immune      12 strains, of the bacterium        associate in Longman’s laboratory.
        system and gut health. Both of       Odoribacter splanchnicus, showed
        these are disrupted in ulcerative    clear signs of this immune          Source: Cornell University

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