The Role of Mucus Barrier in Ulcerative Colitis Pathogenesis Using Proteomics

The treatment of ulcerative colitis (UC) has changed over the last decade. It is extremely important to optimize the therapies which are available nowadays and commonly used in daily clinical practice, as well as to stimulate the search for more powerful drugs for the induction and maintenance of sustained and durable remission, thus preventing further complications. Therefore, it is mandatory to identify the patients' prognostic variables associated with an aggressive clinical course and to test the most potent therapies accordingly.To date, the conventional therapeutic approach based on corticosteroids, salicylates (sulfasalazine, 5-aminosalicylic acid) or immunosuppressive agents is commonly used as a first step to induce and to maintain remission. However, in recent years, knowledge of new pathogenetic mechanisms of ulcerative colitis have allowed us to find new therapeutic targets leading to the development of new treatments that directly target proinflammatory mediators, such as TNF-alpha, cytokines, membrane migration agents, cellular therapies.The aim of this review is to provide the most significant data regarding the therapeutic role of drugs in UC and to give an overview of biological and experimental drugs that will become available in the near future. In particular, we will analyse the role of these drugs in the treatment of acute flare and maintenance of UC, as well as its importance in mucosal healing and in treating patients at a high risk of relapse.

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THE ROLE OF SEVERAL CYTOKINES IN THE PATHOGENESIS OF AUTOIMMUNE INFLAMMATION IN PATIENTS WITH ULCERATIVE COLITIS

10.26226/morressier.59a6b34bd462b80290b559d4 ◽

2017 ◽

Author(s):

Alina Valeeva

Keyword(s):

Ulcerative Colitis ◽

Autoimmune Inflammation

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Faculty Opinions recommendation of Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.735406375.793564678 ◽

2019 ◽

Author(s):

Jonathan Braun

Keyword(s):

Ulcerative Colitis ◽

Early Event ◽

Mucus Barrier

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10 THE ROLE OF DIETARY L-SERINE IN THE REGULATION OF INTESTINAL MUCUS BARRIER DURING INFLAMMATION

Inflammatory Bowel Diseases ◽

10.1093/ibd/zaa010.110 ◽

2020 ◽

Vol 26 (Supplement_1) ◽

pp. S42-S42

Author(s):

Kohei Sugihara ◽

Nobuhiko Kamada

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Gut Microbiota ◽

Control Diet ◽

Bacterial Strains ◽

Germ Free ◽

Intestinal Mucus ◽

Gnotobiotic Mice ◽

Mucus Barrier

Abstract Background Recent accumulating evidence suggests that amino acids have crucial roles in the maintenance of intestinal homeostasis. In inflammatory bowel disease (IBD), amino acid metabolism is changed in both host and the gut microbiota. Among amino acids, L-serine plays a central role in several metabolic processes that are essential for the growth and survival of both mammalian and bacterial cells. However, the role of L-serine in intestinal homeostasis and IBD remains incompletely understood. In this study, we investigated the effect of dietary L-serine on intestinal inflammation in a murine model of colitis. Methods Specific pathogen-free (SPF) mice were fed either a control diet (amino acid-based diet) or an L-serine-deficient diet (SDD). Colitis was induced by the treatment of dextran sodium sulfate (DSS). The gut microbiome was analyzed by 16S rRNA sequencing. We also evaluate the effect of dietary L-serine in germ-free mice and gnotobiotic mice that were colonized by a consortium of non-mucolytic bacterial strains or the consortium plus mucolytic bacterial strains. Results We found that the SDD exacerbated experimental colitis in SPF mice. However, the severity of colitis in SDD-fed mice was comparable to control diet-fed mice in germ-free condition, suggesting that the gut microbiota is required for exacerbation of colitis caused by the restriction of dietary L-serine. The gut microbiome analysis revealed that dietary L-serine restriction fosters the blooms of a mucus-degrading bacterium Akkermansia muciniphila and adherent-invasive Escherichia coli in the inflamed gut. Consistent with the expansion of mucolytic bacteria, SDD-fed mice showed a loss of the intestinal mucus layer. Dysfunction of the mucus barrier resulted in increased intestinal permeability, thereby leading to bacterial translocation to the intestinal mucosa, which subsequently increased the severity of colitis. The increased intestinal permeability and subsequent bacterial translocation were observed in SDD-fed gnotobiotic mice that colonized by mucolytic bacteria. In contrast, dietary L-serine restriction did not alter intestinal barrier integrity in gnotobiotic mice that colonized only by non-mucolytic bacteria. Conclusion Our results suggest that dietary L-serine regulates the integrity of the intestinal mucus barrier during inflammation by limiting the expansion of mucus degrading bacteria.

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The Synergistic Role of Diet and Exercise in the Prevention, Pathogenesis, and Management of Ulcerative Colitis: An Underlying Metabolic Mechanism

Nutrition and Metabolic Insights ◽

10.1177/1178638819834526 ◽

2019 ◽

Vol 12 ◽

pp. 117863881983452 ◽

Cited By ~ 1

Author(s):

Jonah Stavsky ◽

Radhashree Maitra

Keyword(s):

Ulcerative Colitis ◽

Aerobic Exercise ◽

Exercise Frequency ◽

Simultaneous Reduction ◽

Diet And Exercise ◽

Literature Reviews ◽

Amino Acid Intake ◽

Metabolic Mechanism ◽

Immunological Research

Ulcerative colitis (UC) is a biologically complex condition characterized by chronic, relapsing inflammation of the gastrointestinal tract. The relative incidence of this debilitating condition is increasing and sociologically damaging outcomes are a continued reality. Several etiological theories for UC are currently under investigation, spanning between genetic and environmental determinants. From an environmental perspective, previous literature reviews have demonstrated the independent effectiveness of specific diet and exercise patterns in modifying UC immuno-pathophysiology. This article explores the synergistic role of diet and aerobic exercise in the prevention, pathogenesis, and management of UC in the context of recent immunological research. Through a unifying mechanism—that is, microbial influence of colonic inflammation and immuno-pathophysiology—the simultaneous reduction of pro-inflammatory dietary sulfurous amino acid intake (ie methionine, cysteine, homocysteine, and taurine) and the upregulation of aerobic exercise frequency (which spurs the colonization of anti-inflammatory butyrate, acetate, and propionate producing microbial taxa) demonstrate the clinical efficacy of incorporating both diet and exercise modifications for UC prevention and management through pathogenic alterations.

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Role of Probiotics and Their Metabolites in Inflammatory Bowel Diseases (IBDs)

Gastroenterology Insights ◽

10.3390/gastroent12010006 ◽

2021 ◽

Vol 12 (1) ◽

pp. 56-66

Author(s):

Toumi Ryma ◽

Arezki Samer ◽

Imene Soufli ◽

Hayet Rafa ◽

Chafia Touil-Boukoffa

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Symptoms ◽

Therapeutic Potential ◽

Short Chain Fatty Acids ◽

Active Metabolites ◽

Complex Disorders ◽

Inflammatory Bowel

Inflammatory Bowel Disease (IBD) is a term used to describe a group of complex disorders of the gastrointestinal (GI) tract. IBDs include two main forms: Crohn’s Disease (CD) and Ulcerative Colitis (UC), which share similar clinical symptoms but differ in the anatomical distribution of the inflammatory lesions. The etiology of IBDs is undetermined. Several hypotheses suggest that Crohn’s Disease and Ulcerative Colitis result from an abnormal immune response against endogenous flora and luminal antigens in genetically susceptible individuals. While there is no cure for IBDs, most common treatments (medication and surgery) aim to reduce inflammation and help patients to achieve remission. There is growing evidence and focus on the prophylactic and therapeutic potential of probiotics in IBDs. Probiotics are live microorganisms that regulate the mucosal immune system, the gut microbiota and the production of active metabolites such as Short-Chain Fatty Acids (SCFAs). This review will focus on the role of intestinal dysbiosis in the immunopathogenesis of IBDs and understanding the health-promoting effects of probiotics and their metabolites.

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Protective role of berberine on ulcerative colitis through modulating enteric glial cells–intestinal epithelial cells–immune cells interactions

Acta Pharmaceutica Sinica B ◽

10.1016/j.apsb.2019.08.006 ◽

2020 ◽

Vol 10 (3) ◽

pp. 447-461 ◽

Cited By ~ 10

Author(s):

Heng Li ◽

Chen Fan ◽

Huimin Lu ◽

Chunlan Feng ◽

Peilan He ◽

...

Keyword(s):

Ulcerative Colitis ◽

Epithelial Cells ◽

Glial Cells ◽

Immune Cells ◽

Intestinal Epithelial Cells ◽

Protective Role ◽

Intestinal Epithelial ◽

Enteric Glial Cells

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Serpin B1 protects colonic epithelial cell via blockage of neutrophil elastase activity and its expression is enhanced in patients with ulcerative colitis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00292.2011 ◽

2012 ◽

Vol 302 (10) ◽

pp. G1163-G1170 ◽

Cited By ~ 20

Author(s):

Kazuhiko Uchiyama ◽

Yuji Naito ◽

Tomohisa Takagi ◽

Katsura Mizushima ◽

Yasuko Hirai ◽

...

Keyword(s):

Ulcerative Colitis ◽

Mrna Expression ◽

Real Time ◽

Neutrophil Elastase ◽

Colonic Mucosa ◽

Clinical Samples ◽

Active Ulcerative Colitis ◽

Inflammatory Infiltration ◽

Serpin B1

Serpin B1 is a monocyte neutrophil elastase (NE) inhibitor and is one of the most efficient inhibitors of NE. In the present study, we investigated the role of serpin B1 in the pathogenesis of ulcerative colitis by using clinical samples and an experimental model. The colonic expression of serpin B1 was determined by real-time polymerase chain reaction (PCR), Western blot analysis, and immunohistological studies in both normal and inflamed mucosa from patients with ulcerative colitis. Serpin B1 mRNA expression was determined by real-time PCR in the mouse dextran sodium sulfate (DSS)-induced colitis model. Young adult mouse colonic epithelial (YAMC) cells were used to determine the role of serpin B1. Serpin B1 gene transfected YAMC cells were treated with H2O2 to measure cell viability. The expression of NE was determined in YAMC cells treated with H2O2. NE-silenced YAMC cells were also treated with H2O2 and then measured for viability. Upregulated expression of serpin B1 in colonic mucosa was confirmed from patients with active ulcerative colitis. Immunohistochemical studies showed that serpin B1 expression was localized not only in inflammatory infiltration cells but also in epithelial cells. Serpin B1 mRNA expression was also increased in colonic mucosa of mouse DSS-induced colitis. Serpin B1-transfected YAMC cells were resistant against the treatment of H2O2. H2O2 treatment significantly induced NE in YAMC cells, and NE-silenced YAMC cells were also resistant against the treatment of H2O2. These results suggest that serpin B1 may be a novel marker of active ulcerative colitis and may play an important role in the pathogenesis of inflammatory bowel disease.

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