Background & Aims: Expression of mucin MUC2, the structural component of the colonic mucus layer, is lowered in inflammatory bowel disease. Our aim was to obtain insight in the role of Muc2 in epithelial protection. Methods: Muc2 knockout (Muc2^−/−) and Muc2 heterozygous (Muc2^+/−) mice were characterized and challenged by a colitis-inducing agent, dextran sulfate sodium (DSS). We monitored clinical symptoms, intestinal morphology, and differences in intestine-specific protein and messenger RNA levels. Results: The Muc2^−/− mice showed clinical signs of colitis (as of 5 weeks), aggravating as the mice aged. Microscopic analysis of the colon of Muc2^−/− mice showed mucosal thickening, increased proliferation, and superficial erosions. Colonic goblet cells in the Muc2^−/− mice were negative for Muc2, but trefoil factor 3 was still detectable. In Muc2^−/− mice, transient de novo expression of Muc6 messenger RNA was observed in the distal colon. On day 2 of DSS treatment, the histologic damage was more severe in Muc2^+/− versus wild-type (Muc2^+/+) mice, but the disease activity index was not yet different. By day 7, the disease activity index and histologic score were significantly elevated in Muc2^+/− versus Muc2^+/+ mice. The disease activity index of the Muc2^−/− mice was higher (versus both Muc2^+/+ and Muc2^+/− mice) throughout DSS treatment. The histologic damage in the DSS-treated Muc2^−/− mice was different compared with Muc2^+/+ and Muc2^+/− mice, with many crypt abscesses instead of mucosal ulcerations. Conclusions: This study shows that Muc2 deficiency leads to inflammation of the colon and contributes to the onset and perpetuation of experimental colitis.

OBJECTIVE: Sequelae of academic underachievement, behavioral problems, and poor executive function (EF) have been extensively reported for very preterm (≤33 weeks' gestation) and/or very low birth weight (VLBW) (≤1500 g) children. Great variability in the published results, however, hinders the field in studying underlying dysfunctions and developing intervention strategies. We conducted a quantitative meta-analysis of studies published between 1998 and 2008 on academic achievement, behavioral functioning, and EF with the aim of providing aggregated measures of effect size for these outcome domains.

SCFAs (short-chain fatty acids), fermentation products of bacteria, influence epithelial-specific gene expression. We hypothesize that SCFAs affect goblet-cell-specific mucin MUC2 expression and thereby alter epithelial protection. In the present study, our aim was to investigate the mechanisms that regulate butyrate-mediated effects on MUC2 synthesis. Human goblet cell-like LS174T cells were treated with SCFAs, after which MUC2 mRNA levels and stability, and MUC2 protein expression were analysed. SCFA-responsive regions and cis-elements within the MUC2 promoter were identified by transfection and gel-shift assays. The effects of butyrate on histone H3/H4 status at the MUC2 promoter were established by chromatin immunoprecipitation. Butyrate (at 1 mM), as well as propionate, induced an increase in MUC2 mRNA levels. MUC2 mRNA levels returned to basal levels after incubation with 5–15 mM butyrate. Interestingly, this decrease was not due to loss of RNA stability. In contrast, at concentrations of 5–15 mM propionate, MUC2 mRNA levels remained increased. Promoter-regulation studies revealed an active butyrate-responsive region at −947/−371 within the MUC2 promoter. In this region we identified an active AP1 (c-Fos/c-Jun) cis-element at −818/−808 that mediates butyrate-induced activation of the promoter. Finally, MUC2 regulation by butyrate at 10–15 mM was associated with increased acetylation of histone H3 and H4 and methylation of H3 at the MUC2 promoter. In conclusion, 1 mM butyrate and 1–15 mM propionate increase MUC2 expression. The effects of butyrate on MUC2 mRNA are mediated via AP-1 and acetylation/methylation of histones at the MUC2 promoter.