The Role of Environmental Factors in the Pathogenesis of Inflammatory Bowel Diseases

Shouval, Dror S.; Rufo, Paul A.

doi:10.1001/jamapediatrics.2017.2571

Cited by 135 publications

(98 citation statements)

References 93 publications

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“…The incidence and prevalence of IBD is increasing worldwide and is associated with significant healthcare utilisation in the United States . Although the exact aetiology of IBD remains unclear, IBD is speculated to arise from a complex interaction between genetic susceptibility, derangements in immune homeostasis, inappropriate responses to gut microflora and various environmental triggers . Increasing evidence has proposed that vitamin D plays a protective role in the pathogenesis of inflammatory bowel disease .…”

Section: Introductionmentioning

confidence: 99%

“…2 Although the exact aetiology of IBD remains unclear, IBD is speculated to arise from a complex interaction between genetic susceptibility, derangements in immune homeostasis, inappropriate responses to gut microflora and various environmental triggers. [3][4][5][6][7] Increasing evidence has proposed that vitamin D plays a protective role in the pathogenesis of inflammatory bowel disease. 8,9 Vitamin D has been shown to maintain gut epithelial barrier integrity against inflammatory and pathogenic stimuli.…”

Section: Introductionmentioning

confidence: 99%

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Systematic review with meta‐analysis: association of vitamin D status with clinical outcomes in adult patients with inflammatory bowel disease

Gubatan

Chou

Nielsen

et al. 2019

Aliment Pharmacol Ther

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Summary Background Vitamin D deficiency is highly prevalent among patients with IBD, however, data on its association with clinical outcomes are conflicting. Aim To perform a systematic review and meta‐analysis to explore the association of low vitamin D status with clinical outcomes in patients with IBD. Methods We searched PubMed, Embase, Scopus and Web of Science from inception to February 2018 for observational studies evaluating the association of low 25(OH)D status on IBD disease activity, mucosal inflammation, clinical relapse and quality of life. Odds ratios (ORs) were pooled and analysed using a random effects model. Results Twenty‐seven studies were eligible for inclusion comprising 8316 IBD patients (3115 ulcerative colitis, 5201 Crohn's disease). Among IBD patients, low 25(OH)D status was associated with increased odds of disease activity (OR 1.53, 95% CI 1.32‐1.77, I2 = 0%), mucosal inflammation (OR 1.25, 95% CI 1.06‐1.47, I2 = 0%), low quality of life (QOL) scores (OR 1.30, 95% CI 1.06‐1.60, I2 = 0%) and future clinical relapse (OR 1.23, 95% CI 1.03‐1.47, I2 = 0%). In subgroup analysis, low vitamin D status was associated with Crohn's disease activity (OR 1.66, 95% CI 1.36‐2.03, I2 = 0%), mucosal inflammation (OR 1.39, 95% CI 1.03‐1.85, I2 = 0%), clinical relapse (OR 1.35, 95% CI 1.14‐1.59, I2 = 0%), and low QOL scores (OR 1.25, 95% CI 1.04‐1.50, I2 = 0%) and ulcerative colitis disease activity (OR 1.47, 95% CI 1.03‐2.09, I2 = 0%) and clinical relapse (OR 1.20, 95% 1.01‐1.43, I2 = 0%). Conclusions Low 25(OH)D status is a biomarker for disease activity and predictor of poor clinical outcomes in IBD patients.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Systematic review with meta‐analysis: association of vitamin D status with clinical outcomes in adult patients with inflammatory bowel disease

Gubatan

Chou

Nielsen

et al. 2019

Aliment Pharmacol Ther

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“…Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn’s disease, are characterized by chronic, progressive, and relapsing intestinal inflammation . Multiple factors, such as genetic susceptibility, immune dysregulation driven by a response to commensal flora, environmental factors and impaired intestinal epithelial barrier, contribute to the etiology of IBD.…”

Section: Introductionmentioning

confidence: 99%

“…Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease, are characterized by chronic, progressive, and relapsing intestinal inflammation. 1,2 Multiple factors, such as genetic susceptibility, immune dysregulation driven by a response to commensal flora, environmental factors and impaired intestinal epithelial barrier, contribute to the etiology of IBD. Recent clinical and experimental studies have verified the importance of intestinal barrier function despite the controversy on whether increased intestinal permeability is a causative event or merely a consequence of the inflammatory milieu in IBD.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological activation of ERβ by arctigenin maintains the integrity of intestinal epithelial barrier in inflammatory bowel diseases

Yue

et al. 2019

FASEB j.

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are contributed equally to this work.Abbreviations: AAV, adeno-associated virus; BSA, bovine serum albumin; CD, Crohn's disease; DAI, disease activity index; DMEM, Dulbecco's modified eagle medium; DSS, dextran sulfate sodium; ERβ, estrogen receptor β; E2, 17β-estradiol; ELISA, enzyme-linked immunosorbent assay; FBS, fetal bovine serum; HSP90, heat shock protein 90; HBSS, Hank's balanced salt solution; IBD, inflammatory bowel diseases; IL-1β, interleukin-1β; IFN-γ, Interferon-γ; IL-6, interleukin-6; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; MPO, myeloperoxidase; MLCK, myosin light chain Abstract Intestinal epithelial barrier dysfunction is deeply involved in the pathogenesis of inflammatory bowel diseases (IBD). Arctigenin, the main active constituent in Fructus Arctii (a traditional Chinese medicine), has previously been found to attenuate colitis induced by dextran sulfate sodium (DSS) in mice. The present study investigated whether and how arctigenin protects against the disruption of the intestinal epithelial barrier in IBD. Arctigenin maintained the intestinal epithelial barrier function of mice with DSS-and TNBS-induced colitis. In Caco-2 and HT-29 cells, arctigenin lowered the monolayer permeability, increased TEER, reversed the abnormal expression of tight junction proteins, and restored the altered localization of F-actin induced by TNF-α and IL-1β. The specific antagonist PHTPP or shRNA of ERβ largely weakened the protective effect of arctigenin on the epithelial barrier function of Caco-2 and HT-29 cells. Molecular docking demonstrated that arctigenin had high affinity for ERβ mainly through hydrogen bonds as well as hydrophobic effects, and the protective effect of arctigenin on the intestinal barrier function was largely diminished in ERβ-mutated (ARG346 and/or GLU305) Caco-2 cells. Moreover, arctigenin-blocked TNF-α induced increase of the monolayer permeability in Caco-2 and HT-29 cells and the activation of myosin light chain kinase (MLCK)/myosin light chain (MLC) pathway in an ERβ-dependent manner. ERβ deletion in colons of mice with DSS-induced colitis resulted in a significant attenuation of the protective effect of arctigenin on the barrier integrity and colon inflammation. Arctigenin maintained the integrity of the intestinal epithelial barrier under IBD by upregulating the expression of tight junction proteins through the ERβ-MLCK/MLC pathway. 3070 |

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“…If clinical therapy fails to produce responsiveness, surgical intervention becomes compulsory. The downside of IBD is that it could well develop into colorectal carcinoma or other cancers in the gut [1][2][3][4][5][6][7][8].…”

Section: Inflammatory Bowel Disease (Ibd)mentioning

confidence: 99%

CCR6-CCL20 Axis in IBD: What have we learnt in the past 20 years?

Ranasinghe¹,

Eri²

2018

Preprint

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Inflammatory bowel disease (IBD) is a CC chemokine receptor 6 (CCR6) -associated immune mediated disorder which has attracted an extensive superfluity of experimental analyses. IBD has come to the fore of varied scrutinizing owing to its complexity by nature for comprising of two synergistic sub phenotypes; Crohn's disease (CD) and Ulcerative colitis (UC). Both these disease entities cause potent immune dysregulation followed by intense tissue damage within the gut mucosal system, initiating symptoms which are severely debilitating. Multiple causative factors are said to be responsible for IBD but direct immune dysfunction is kindled by overplay of innate and adaptive immune responses produced against a pathogenic microbial attack through the weakened or leaky gut epithelial barrier. Once immune homeostasis is not achieved by tolerating agents, the self-assertive adaptive immunity mobilize its various T and B cell cohorts initializing their allied immune mechanisms by vigorously deploying them towards the site of infection. CCR6 and its unique solitary ligand CC-chemokine ligand 20 (CCL20) are small protein molecules which are abundantly expressed by T and B lymphocytes and act as chemotactic immune-modulatory envoys that help in the deployment of the effector lymphocyte arm of the immune system, producing two directly opposing outcomes in IBD. This dichotomous immunity consists of either immune tolerance or inflammation which then develops into a chronic state, remaining catatonic to inherent immunity or targeted clinical therapy. In this review, we have chronologically identified a plethora of experimental studies radiating into 14 different compartments highlighted in the visual depiction which have employed both mouse models and clinical subjects spanning a period of nearly two decades. In doing so, we expect the research community would further benefit by tracing through the history, thereby understanding the CCR6 -CCL20 axis in IBD and identifying the gaps in literature which can be fortuitously filled in the future.Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted:

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The Role of Environmental Factors in the Pathogenesis of Inflammatory Bowel Diseases

Cited by 135 publications

References 93 publications

Systematic review with meta‐analysis: association of vitamin D status with clinical outcomes in adult patients with inflammatory bowel disease

Systematic review with meta‐analysis: association of vitamin D status with clinical outcomes in adult patients with inflammatory bowel disease

Pharmacological activation of ERβ by arctigenin maintains the integrity of intestinal epithelial barrier in inflammatory bowel diseases

CCR6-CCL20 Axis in IBD: What have we learnt in the past 20 years?

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