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Scott Snapper – IBDs and gut microbiota

The microbiome
has been studied for decades related to IBD and it’s been known for a long time
in mouse models of IBD that bacteria matter, because in most models of mouse if you don’t have microbes
they don’t get disease and it doesn’t for the
largest number of models and there are over 50 known bacteria
in inflammatory bowel disease. In humans, deep microbial genotyping has clearly shown that if you compare IBD patients or ulcerative colitis
or Crohn’s disease to healthy controls there’s altered diversity. So there’s a reduced diversity and this is true for both
ulcerative colitis and Crohn’s. It’s still not clear: is the change in diversity
a cause or an effect of the underlying inflammation
that people have? Although some studies – and a very large study funded by
the Crohn’s & Colitis Foundation, in Cell Host & Microbe – showed that even at the time of diagnosis, at the initial diagnosis the microbiota has already changed. Again the question: is it possible that the altered diversity actually is a driver of the inflammation as opposed to the inflammation
is a driver of the altered diversity? There have been a number of,
I would say, basic and translational studies that are trying to manipulate
the microbiota for therapeutic effects. People have isolated groups of bacteria, where groups of bacteria
can induce regulatory T-cells and there are companies trying to develop
these bacteria as a therapeutic since one might imagine you can give
these healthy bacteria that induce regulatory cells to patients. This is all, although there have
been lots of mouse work, there’s increasing numbers of studies
that are planned for humans. The human studies on microbiota
have been looked in two different ways. One is fecal transplant. Fecal microbial transplant works very effectively for C. difficile infections and there’s been the question: “does it work for inflammatory
bowel disease?” The jury’s not out on it: it’s probably not going to be
the magic bullet because fecal microbial transplants is giving
a large diversity of organisms as opposed to only
“the good ones versus the bad ones” but there happened some studies and in particular one from Australia
published in The Lancet last year, that really showed the effectiveness of five days a week for six to eight weeks that was effective for ulcerative colitis, but studies on fecal transplant
are still going on and I’d say the jury’s still out.

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