Microbiota and mucosal defense in IBD: an update

Figures & data

Table 1. Arguments for the key role of microbes in IBD.

● Gnotobiotic mice lacking a microbiota are refractory in experimental colitis models

● Antibiotics given in early life increase the risk of IBD

● IBD is localized in segments with highest bacterial load

● Surgical diversion is associated with distal mucosal healing, reversed by instillation of fecal contents

● Luminal and mucosal microbiota is abnormal in IBD

● Cellular and humoral immunity is directed against bacterial, not cellular antigens

● Antimicrobial peptides (AMP´s) and antibacterial activity in the intestinal mucosa are altered in IBD

● Important risk genes, including bacterial recognition (NOD2), autophagy (ATG16L1) and others, affect the Paneth cells, which are defending the small intestine against bacterial invasion

● A compromised mucus barrier leads to mucosal inflammation in the mouse (and man?)

● Antibiotics are effective in some instances of IBD, including the postoperative state or pouchitis

● Probiotics and fecal transfer may induce or maintain remission in IBD

Figure 1. The different levels of mucosal defense against invasion of the microbiota. This expert review will focus on level I.

Figure 2. Possible interactions of the gut microbiota with the mucosal barrier, ultimately leading to IBD. In the left scenario, the microbiota is altered, leading to barrier defects and inflammation in a susceptible host. In the right scenario, primary mucosal barrier defects lead to altered gut microbiota, and eventually an onset of inflammation.

Table 2. Arguments for microbes being hen or egg in IBD.

Primary role	Secondary role
● Adherent and invading bacteria in mucosa	● Significant impact of inflammation on microbiome
● Proven role of protective species like Faecalibacterium prausnitzii	● Modulation by the host through genetics and environment (nutrition)
● Dysbiosis persists even in long-term remission	● Role of diminished diversity unclear and not specific for IBD
● In experimental models feces may transfer inflammation	● Genetic links associated with defective barrier
● Fecal transfer effective in UC	● No induction of colitis following fecal transfer from IBD patients to mice or humans

Figure 3. Small-intestinal barrier function during homeostasis and IBD. During homeostasis, the gut microbiota is held at a distance through a mucus layer that is loaded with antimicrobial peptides (AMPs), which are predominantly produced by Paneth cells. During IBD, decreased diversity of the gut microbiota is consistently observed over most studies. Moreover, reduced antimicrobial activity and adherent-invasive E. coli (AIEC) are observed in ileal biopsies, which may be a result of defective Paneth cell function in Crohn’s disease.

Figure 4. Colonic barrier function during homeostasis and IBD. During homeostasis, gut microbiota colonization is restricted to the outer mucus layer. Beneficial commensal bacteria, such as Lactobacillus, Bifidobacterium, Ruminococcaceae, Bacteroides thetaiotaomicron (B. theta), Faecalibacterium prausnitzii (F. prausnitzii) and Peptostreptococcus russellii (P. russellii) stimulate and maintain active mucosal barrier function. During IBD, bacterial diversity is decreased, the inner colonic mucus layer is penetrable to bacteria (ulcerative colitis) and a biofilm, mainly consisting of Bacteroides fragilis, can be observed at the mucosa (Crohn’s disease). In mice, several genetic defects recapitulate the clinical signs of ulcerative colitis.