Background The mucus gel layer (MGL) lining the colon is integral to exclusion of bacteria and maintaining intestinal homeostasis in health and disease. Some MGL defects allowing bacteria to directly contact the colonic surface are commonly observed in ulcerative colitis (UC). The major macromolecular component of the colonic MGL is the secreted gel-forming mucin MUC2, whose expression is essential for homeostasis in health. In UC, another gel-forming mucin, MUC5AC, is induced. In mice, Muc5ac is protective during intestinal helminth infection. Here we tested the expression and functional role of MUC5AC/Muc5ac in UC biopsies and murine colitis. Methods We measured MUC5AC/Muc5ac expression in UC biopsies and in dextran sulfate sodium (DSS) colitis. We performed DSS colitis in mice deficient in Muc5ac (Muc5ac-/-) to model the potential functional role of Muc5ac in colitis. To assess MGL integrity, we quantified bacterial-epithelial interaction and translocation to mesenteric lymph nodes. Antibiotic treatment and 16S rRNA gene sequencing were performed to directly investigate the role of bacteria in murine colitis. Results Colonic MUC5AC/Muc5ac mRNA expression increased significantly in active UC and murine colitis. Muc5ac-/- mice experienced worsened injury and inflammation in DSS colitis compared with control mice. This result was associated with increased bacterial-epithelial contact and translocation to the mesenteric lymph nodes. However, no change in microbial abundance or community composition was noted. Antibiotic treatment normalized colitis severity in Muc5ac-/- mice to that of antibiotic-treated control mice. Conclusions MUC5AC/Muc5ac induction in the acutely inflamed colon controls injury by reducing bacterial breach of the MGL.

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Aim:In cases of anastomotic failure after colorectal (CRA) or coloanal anastomosis (CAA), revision of the anastomosis is an ambitious surgical option that can be proposed in order to maintain bowel continuity. Our aim was to assess postoperative morbidity, risk of failure and risk factor for failure in patients after CRA or CAA.Methods: All consecutive patients who underwent redo-CRA/CAA in our institution between 2007-2018 were retrospectively included. The success of redo-CRA/CAA was defined by the restoration of bowel continuity 12 months after the surgery.Results: Two hundred patients (114 male: 57%) were analyzed. The indication for redo-CRA/CAA was chronic pelvic infection in 74 patients (37%), recto-vaginal or urinary fistula in 59 patients (30%), anastomotic stenosis in 36 patients (18%) and redo anastomosis after previous anastomosis takedown in 31 patients (15%). Twenty-three percent of the patients developed a severe postoperative complication. Anastomotic leakage was diagnosed in 39 patients (20%). One-year-success of the redo-CRA/CAA was obtained in 80% of patients. In multivariate analysis, only obesity was associated with redo-CRA/ CAA failure (p = 0.042). We elaborated a pre-operative predictive score of success using the four variables: male sex, age > 60 years, obesity and history of pelvic radiotherapy.The success of redo-CRA/CAA was 92%, 86%, 80% and 62% for a preoperative predictive score value of 0, 1, 2 and ≥3, respectively (p = 0.010). Conclusions:In case of failure of primary CRA/CAA, bowel continuity can be saved in 4 out of 5 patients by redo-CRA/CAA despite 23% suffering severe postoperative morbidity.

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Inflammatory bowel disease (IBD) is a chronic relapsing-remitting immune-mediated disorder affecting the gut. It is common in Westernized regions and is increasing in incidence in developing countries. At a molecular level, intrinsic deficiencies in epithelial integrity, mucosal barrier function, and mechanisms of immune response and resolution contribute to the development of IBD. Traditionally two platforms have been utilized for disease modeling of IBD; in-vitro monolayer cell culture and in-vivo animal models. Both models have limitations, including cost, lack of representative cell types, lack of complexity of cellular interactions in a living organism, and xenogeneity. Organoids, three-dimensional cellular structures which recapitulate the basic architecture and functional processes of the organ of origin, hold potential as a third platform with which to investigate the pathogenesis and molecular defects which give rise to IBD. Organoids retain the genetic and transcriptomic profile of the tissue of origin over time and unlike monolayer cell culture can be induced to differentiate into most adult intestinal cell types. They may be used to model intestinal host-microbe interactions occurring at the mucosal barrier, are amenable to genetic manipulation and can be co-cultured with other cell lines of interest. Bioengineering approaches may be applied to render a more faithful representation of the intestinal epithelial niche. In this review, we outline the concept of intestinal organoids, discuss the advantages and disadvantages of the platform comparative to alternative models, and describe the translational applications of organoids in IBD.