Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine characterized by a compromised intestinal epithelial barrier. Mucin glycans are crucial in preserving barrier function during bacterial infections, although the underlying mechanisms remain largely unexplored. A cohort comprising 15 patients diagnosed with UC and 15 healthy individuals was recruited. Stool samples were collected to perform 16S rRNA gene sequencing, while biopsy samples were subjected to nanocapillary liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) to assess O-glycosylation. Gene expression was evaluated through qPCR analysis and Western blotting. Furthermore, animal experiments were conducted to investigate the effects of Escherichia coli and/or O-glycan inhibitor benzyl-α-GalNAc on the development of colitis in mice. Our findings revealed that the mucus barrier was disrupted during the early stages of UC, while the MUC2 protein content remained unaltered. Additionally, a noteworthy reduction in the o-glycosylation of MUC2 was observed, along with significant changes in the intestinal microbiota during the early stages of UC. These changes included a decrease in intestinal species richness and an increase in the abundance of Escherichia coli (E. coli). Moreover, subsequent to the administration of galactose or o-glycan inhibitor to intestinal epithelial cells, it was observed that the cell culture supernatant had the ability to modify the proliferation and adhesive capacity of E. coli. Furthermore, when pathogenic E. coli or commensal E. coli were cocultured with intestinal epithelium, both strains elicited activation of the NF-KB signaling pathway in epithelial cells and facilitated the expression of serine protease in comparison to the untreated control. Consistently, the inhibition of o-glycans has been observed to enhance the pathogenicity of E. coli in vivo. Furthermore, a correlation has been established between the level of o-glycans and the development of ulcerative colitis. Specifically, a reduction in the O-glycan content of MUC2 cells has been found to increase the virulence of E. coli, thereby compromising the integrity of the intestinal epithelial barrier. Together, there exist complex interactions between the intestinal epithelium, o-glycans, and the intestinal microbiota, which may inform the development of novel therapeutic strategies for the treatment of ulcerative colitis.

Background: Crohn's disease (CD) is an irreversible inflammatory disorder, characterized by alternating periods of relapse and remission. It is particularly important to predict clinical relapses in patients with CD because patients in remission could relapse frequently in a randomized way. Small intestinal bacterial overgrowth (SIBO) is a symptom of gut microbial dysbiosis and is commonly observed in patients with CD, which may affect disease course. The present research was carried out to establish whether SIBO is linked to the subsequent clinical relapse of CD. Methods: This retrospective observational cohort research included consecutive patients (>= 18 years) with quiescent CD who underwent lactulose hydrogen-methane breath test to diagnose SIBO managed at Jinling Hospital in China from January 2016 to June 2020. We assessed demographic data, laboratory parameters, SIBO and clinical characteristics including disease location and behavior, surgical history and current and previous medication at baseline and analyzed these data to identify factors associated with clinical relapse. Patients were followed up for 18 months and assessed for the Crohn's Disease Activity Index (CDAI) scores, treatment escalation, and disease progression to determine the primary endpoint of clinical relapse. Results: Of the 73 enrolled patients, 34 (46.6%) were positive for SIBO. Twenty-seven (37.0%) patients experienced clinical relapse within 18 months (median time of relapse: 13.9 months). SIBO in the relapse group was considerably elevated compared to the non-relapse group (63.0% vs. 37.0%, P=0.032). The multivariate Cox regression analysis showed that SIBO [hazard ratio (HR) 2.79, P=0.017] and penetrating disease behavior (HR 3.66, P=0.040) were the sole individual risk elements for relapse in patients with quiescent CD. Conclusions: This study indicated that SIBO was highly prevalent in patients with CD, and was independently linked to clinical relapse in quiescent patients. Detecting SIBO may be a valuable option for the prognostic assessment of patients in clinical remission.