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      MUC2 and related bacterial factors: Therapeutic targets for ulcerative colitis

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          Abstract

          The mucin2 (MUC2) mucus barrier acts as the first barrier that prevents direct contact between intestinal bacteria and colonic epithelial cells. Bacterial factors related to the MUC2 mucus barrier play important roles in the response to changes in dietary patterns, MUC2 mucus barrier dysfunction, contact stimulation with colonic epithelial cells, and mucosal and submucosal inflammation during the occurrence and development of ulcerative colitis (UC). In this review, these underlying mechanisms are summarized and updated, and related interventions for treating UC, such as dietary adjustment, exogenous repair of the mucus barrier, microbiota transplantation and targeted elimination of pathogenic bacteria, are suggested. Such interventions are likely to induce and maintain a long and stable remission period and reduce or even avoid the recurrence of UC. A better mechanistic understanding of the MUC2 mucus barrier and its related bacterial factors may help researchers and clinicians to develop novel approaches for treating UC.

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          Most cited references93

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          Ulcerative colitis

          Ulcerative colitis is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. The pathogenesis is multifactorial, involving genetic predisposition, epithelial barrier defects, dysregulated immune responses, and environmental factors. Patients with ulcerative colitis have mucosal inflammation starting in the rectum that can extend continuously to proximal segments of the colon. Ulcerative colitis usually presents with bloody diarrhoea and is diagnosed by colonoscopy and histological findings. The aim of management is to induce and then maintain remission, defined as resolution of symptoms and endoscopic healing. Treatments for ulcerative colitis include 5-aminosalicylic acid drugs, steroids, and immunosuppressants. Some patients can require colectomy for medically refractory disease or to treat colonic neoplasia. The therapeutic armamentarium for ulcerative colitis is expanding, and the number of drugs with new targets will rapidly increase in coming years.
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            A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility.

            Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota, and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome, and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics.
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              Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial.

              Ulcerative colitis (UC) is difficult to treat, and standard therapy does not always induce remission. Fecal microbiota transplantation (FMT) is an alternative approach that induced remission in small series of patients with active UC. We investigated its safety and efficacy in a placebo-controlled randomized trial.
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                Author and article information

                Contributors
                Journal
                EBioMedicine
                EBioMedicine
                EBioMedicine
                Elsevier
                2352-3964
                10 December 2021
                December 2021
                10 December 2021
                : 74
                : 103751
                Affiliations
                [a ]Department of the Second General Surgery, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Heping District, Shenyang, Liaoning 110004, China
                [b ]Innovation Institute, China Medical University, Shenyang, Liaoning 110004, China
                [c ]Department of Gastrointestinal Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110004, China
                Author notes
                [* ]Corresponding author. wushuodong1949@ 123456163.com
                Article
                S2352-3964(21)00545-4 103751
                10.1016/j.ebiom.2021.103751
                8671112
                34902790
                9c6b6fa4-92dd-4c73-a100-893bf1f06690
                © 2021 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 18 September 2021
                : 21 November 2021
                : 30 November 2021
                Categories
                Review

                muc2,mucus barrier,dysbiosis,microbiota transplantation,ulcerative colitis,cac, colitis-associated cancer,ck, cysteine knot,dss, dextransodiumsulfate,er, endoplasmic reticulum,fmt, fecal microbiota transplantation,gf, germ-free,ibd, inflammatory bowel disease,muc2, mucin2,nhe3, na+/h+ exchanger 3,ros, reactive oxygen species,scfas, short-chain fatty acids,tlr, toll-like receptor,tnbs, 2,4,6-trinitrobenzenesulfonic acid,uc, ulcerative colitis,vwd, von willebrand d

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