Probiotic Mixture VSL#3 Alleviates Dextran Sulfate Sodium-induced Colitis in Mice by Downregulating T Follicular Helper Cells

Clinical trials have shown beneficial effects of probiotics on inflammatory bowel diseases (IBD), although the exact mechanism remains unknown. VSL#3, a mixture of 8 probiotic bacteria, has been confirmed to have adjunctive therapeutic effects on colitis. T follicular helper (Tfh) cells, a new separate subset of CD4+ T helper cells, have been proved to play a vital role in autoimmunity. The present study aimed to identify the beneficial effect of the probiotic mixture VSL#3 on the mouse model of colitis by regulating Tfh cells. Dextran sulfate sodium (DSS) was used to induce chronic colitis in C57BL/6 mice. VSL#3 (3x109 live bacteria) was given to C57BL/6 mice every other day for 60 days by gavage. The disease activity index (DAI), histological activity index (HAI), colon length and myeloperoxidase (MPO) activity were detected. Immunofluorescence was used to visualize the location of Tfh cells. Immunoglobulins, Tfh cells and plasma cells were quantified by enzyme-linked immunosorbent assay (ELISA), flow cytometry, real-time PCR or Western blotting. The results showed that after DSS treatment, the humoral immunity was disordered in C57BL/6 mice, with increased IgM, IgG and IgA levels in colonic mucus and increased Tfh cells in mesenteric lymph nodes (MLN). VSL#3 treatment showed anti-inflammatory effects as evidenced by reduced DAI score, HAI score and MPO activity. IgM, IgG and IgA levels were significantly reduced in colon mucus, and the number of Tfh cells was markedly decreased in MLN after VSL#3 treatment. It was concluded that VSL#3 alleviates DSS-induced colitis by downregulating Tfh cells, and Tfh cells may become a potential therapeutic target for IBD.

Risk factors for colorectal neoplasia in patients with underlying inflammatory bowel disease:a multicenter study

Background:This study sought to evaluate the risk factors for the development of colitis-associated neoplasia(CAN)in Chinese patients with inflammatory bowel disease(IBD).Methods:IBD patients who developed CAN between 1999 and 2016 were identified from eight medical centers.In addition to initial pathology evaluation,a CAN diagnosis was confirmed by two expert pathologists.Patients with CAN(n=29)were compared with non-CAN controls(n=87).Matching was performed for gender and IBD type with a ratio of three controls to one subject.Results:Of the 29 patients with CAN,8(27.6%)had colorectal cancer(CRC),20(69.0%)had a final diagnosis of low-grade dysplasia and 1(3.4%)had high-grade dysplasia.Multivariate analysis revealed that an older age at the time of IBD diagnosis and a longer IBD duration were independent risk factors for the development of CAN,with odds ratios of 1.09[95%confidence interval(CI):1.04–1.14,P<0.001]and 1.14(95%CI:1.03–1.27,P=0.013),respectively.Comparison between IBD patients with CRC and those with dysplasia indicated that the former were older at the time of IBD diagnosis(P=0.012)and had longer IBD durations(P=0.019).Conclusions:Older age at the time of IBD diagnosis and longer IBD duration were found to be associated with the development of CAN in IBD patients.