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Introduction: The renin-angiotensin system (RAS) is an important homeostatic pathway, with emerging evidence for the impact of its components on inflammation and fibrosis in gastrointestinal tissues. This review aims to review current knowledge of the physiological mechanism of RAS in inflammatory bowel disease (IBD), and potential therapeutic implications., Areas Covered: An extensive online literature review including Pubmed, Medline, and Google Scholar was undertaken. Discussion on the components of the RAS, localization, and physiological functions in the gastrointestinal tract, preclinical, and clinical data in IBD, and the relation with SARS-Cov-2 are covered in this review., Expert Opinion: RAS inhibition may have a role as anti-fibrotic adjunct therapy. Targeting the local gastrointestinal RAS with novel modes of delivery may be a target for future therapeutics for IBD, given the widespread availability and safety of current options as utilized in other diseases. Further insight into the mechanism and downstream effects of gastrointestinal ACE2 may lead to a better understanding of the pathogenesis of IBD.

Background & Aims: Vitamin D at serum 25(OH)D concentrations above 100 nmol/L is associated with disease remission in patients with IBD, suggesting targeted dosing might be anti-inflammatory. This study aimed to assess the effectiveness, safety and predictors of a 12-week regimen of vitamin D supplementation to achieve such a target in patients with active disease., Methods: In a pilot study, patients with active colitis and a serum 25(OH)D concentration <75 nmol/L were prescribed oral liquid vitamin D supplementation over 12 weeks using a specific protocol with dose adjusted 4-weekly to aim for a target level of 100-125 nmol/L., Results: Five patients each with Crohn's colitis or ulcerative colitis (UC) had mean 25(OH)D concentration 52 (range 27-73 nmol/L). Five reached the targeted level and four 89-95 nmol/L. One withdrew after 4 weeks (88 nmol/L). Target dose was met only in those with BMI <30 kg/m 2 and total dose inversely correlated with initial serum 25(OH)D. One patient had developed a high level at 8 weeks (146 nmol/L) and another new hypercalciuria. There were no serious adverse events attributable to the therapy. Clinical disease activity consistently declined, but faecal calprotectin and circulating markers of inflammation did not., Conclusions: A specified oral vitamin D regimen successfully and safely achieved target or near-target levels, improved symptom-based activity scores, but did not alter objective measures of intestinal or systemic inflammation. A modified version of this dose-escalating regimen would be suitable for a randomised placebo-controlled trial, but does require regular safety monitoring., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Introduction: The relationship between intestinal inflammation and circulating components of the renin-angiotensin system (RAS) is poorly understood., Materials and Methods: Demographic and clinical data were obtained from healthy controls and patients with inflammatory bowel disease (IBD). Plasma concentrations of the classical RAS components (angiotensin-converting enzyme (ACE) and angiotensin II (Ang II)) and alternative RAS components (ACE2 and angiotensin (1-7) (Ang (1-7))) were analysed by radioimmuno- and enzymatic assays. Systemic inflammation was assessed using serum C-reactive protein (CRP), white cell count, platelet count and albumin, and intestinal inflammation by faecal calprotectin., Results: Nineteen healthy controls (11 female; mean age 38 years, range 23-68), 19 patients with Crohn's disease (11 female; aged 45 years, range 23-76) and 15 patients with ulcerative colitis (6 female; aged 42 years, 26-64) were studied. Circulating classical RAS component levels were similar across the three groups, whereas ACE2 activity and Ang (1-7) concentrations were higher in patients with IBD compared to controls (ACE2: 21.5 vs 13.3 pmol/ml/min, p<0.05; Ang (1-7): 22.8 vs 14.1 pg/ml, p<0.001). Ang (1-7) correlated weakly with platelet and white cell counts, but not calprotectin or CRP, in patients with IBD., Conclusions: Circulating components of the alternative RAS are increased in patients with IBD., (© The Author(s) 2014.)

Background: The intestinal vitamin D receptor (VDR) remains poorly characterized in patients with inflammatory bowel disease (IBD). Methods: Colonoscopic biopsies and intestinal resection specimens from the terminal ileum, ascending and sigmoid colon, from patients with and without IBD, were analyzed for VDR mRNA quantification by polymerase chain reaction, and protein localization and semi-quantification by immunohistochemistry. The relationship between VDR and intestinal inflammation, serum 25(OH)D and oral vitamin D intake was elicited. Results: A total of 725 biopsies from 20 patients with Crohn's disease (CD), 15 with ulcerative colitis (UC) and 14 non-IBD controls who underwent colonoscopy were studied. VDR gene expression and protein staining intensity was similar across all three groups, and across the intestinal segments. Sigmoid colon VDR mRNA expression inversely correlated with faecal calprotectin (r = −0.64, p = 0.026) and histological score (r = −0.67, p = 0.006) in UC, and histological score (r = −0.58, p = 0.019) in patients with CD. VDR staining intensity was higher in quiescent than diseased segments. No relationship with serum 25(OH)D or oral vitamin D intake was noted. Immunohistochemical staining of 28 intestinal resection specimens from 15 patients (5 each with CD, UC and non-IBD controls) showed diffuse VDR staining in the mucosa, submucosa and circular muscle. Conclusions: VDR transcript expression and protein staining intensity are inversely related to inflammation in IBD, but unrelated to serum 25(OH)D, and similar to non-IBD controls. Strategies to upregulate intestinal VDR, potentially translating to modulation of disease activity, require investigation. [ABSTRACT FROM AUTHOR]