Role of Intestinal Microbiota in Ulcerative Colitis

Introduction
The mucus layer lining the epithelium of the gastrointestinal tract is important for the protection
of the epithelium in humans. The colonic mucus constitutes a defense barrier, which separates the
intestinal bacterial residents and pathogens from the underlying epithelium. The mucus layer is
rich in gel‐forming mucins, glycoproteins, which provides a matrix for retention of antimicrobial
peptides and immunoglobulins including IgA secreted by the host [29,42] Commensal bacteria
have been found to colonize the colonic mucus layer. However, bacteria are most abundant in the
outer layer of the mucus at the luminal side [22,23]. Previous studies have shown that the
microbial community found in the colonic mucus differs from that of the luminal community
[13,67]. Several microbial characteristics have contributed to the evolvement of this specifically
selected mucosal community. These include the ability of the bacteria to utilize mucin glycans as
energy source, and resistance to nonspecific antimicrobial peptides and specific antimicrobial
immunoglobulins produced by the host [23,25]. Additionally, some bacteria express adhesion
molecules enabling them to bind to the mucin. Many of the adhesion molecules expressed by the
colonic bacteria have mucin glycans as specific epitopes [27,49]. It has previously been suggested
that the glycosylation pattern in mucin, hence the attachment site and energy source for the
colonic bacteria, is an important factor for host selection of a specific mucosal community [23].
Lack or defects in this pattern may allow bacteria to reach the epithelium, and trigger colonic
inflammation.
Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease, which is characterized by
chronic inflammation of the colonic mucosa. UC is usually associated with recurrent attacks and
complete remission of symptoms in the interim [2,28]. The etiology of inflammatory bowel disease
remains an enigma, and no known infectious agent has been demonstrated [37,53]. Human
studies have revealed that UC patients have a colonic mucus layer that has an altered O‐glycan
profile and is significantly thinner than that of healthy subjects, which may select for a different
mucosal microbial profile [33,51]. Consistently, several studies have shown that patients with UC
have an altered bacterial microbiota [16,52,57,58]. The host‐bacterial interaction may thus play a
pivotal role in the pathogenesis of UC.
In vitro models are well‐suited to screen the adhering potency of intestinal microbes. They include
adhesion assays to various components of the intestinal surface: e.g. intestinal mucus [47], mucins
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