4.6 Article

Effects of fiber intake on intestinal pH, transit, and predicted oral mesalamine delivery in patients with ulcerative colitis

Journal

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
Volume 36, Issue 6, Pages 1580-1589

Publisher

WILEY
DOI: 10.1111/jgh.15311

Keywords

Diet; Fiber; Intestinal transit; Mesalamine; pH; Ulcerative colitis

Funding

  1. Ferring Pharmaceuticals Pty Ltd.
  2. Australian Postgraduate Research scholarship fund

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Limited data are available on the effects of fermentable fiber intake on altering intestinal pH and transit in UC patients. This study found that increasing fermentable fiber intake lowered overall and distal pH in healthy controls, and only decreased cecal pH in UC patients. Colonic transit in UC patients varied widely after low-fiber intake but tended to normalize after high fermentable fiber intake. Hypothetical coating dissolution profiles were heterogeneous in UC patients.
Background and Aim Limited data are available on the effects of fermentable fiber in altering intestinal pH and transit to predict efficacy-based delivery profiles of pH-dependent mesalamine coatings in ulcerative colitis (UC). This study aimed to examine regional pH and transit after acute changes in fermentable fiber intake in quiescent UC patients and their effects on drug release systems. Methods In a randomized, double-blind study, 18 patients with quiescent UC and 10 healthy controls were supplied meals high (13 g) or low (<= 2 g) in fermentable fiber and subsequently ingested a wireless pH-motility capsule. After a >= 3-day washout, they crossed over to the other diet. Measurements of intestinal pH and transit were used to predict drug release for the various pH-dependent coatings. Results Increasing fermentable fiber intake lowered overall (median 6.2 [6.1-6.7] vs low: 6.9 [range or interquartile range: 6.4-7.4]; P = 0.01) and distal pH (7.8 [7.3-8.1] vs 8.2 [8.0-8.5]; P = 0.04) in controls. In UC patients, only cecal pH was decreased (high: 5.1 [4.8-5.5] vs low: 5.5 [5.3-5.7]; P < 0.01). Colonic transit in the UC cohort varied widely after a low-fiber intake but tended to normalize after the high fermentable fiber intake. Hypothetical coating dissolution profiles were heterogeneous in UC patients, with a multi-matrix delayed release system having the highest likelihood of patients (20-40%) with incomplete dissolution, and predominant small intestinal dissolution predicted for Eudragit L (94% patients) and S (44-69%). Conclusions Patients with quiescent UC have abnormalities in intestinal pH and transit in response to acute changes in fermentable fiber intake. These have potentially detrimental effects on predicted luminal release patterns of pH-dependent 5-aminosalicylic acid release systems.

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