The Diminished Content of Soluble Mucin as a Potential Contributing Factor to the Development of Chronic Constipation

Abstract

Purpose: The mucus-buffer layer, covering the alimentary tract epithelium, is the major protective mechanism against luminal insults, including HCl/pepsin, and especially in patients colonized by H. pylori or receiving chronic therapy with non-steroidal anti-inflammatory drugs (NSAIDs) setting the stage for mucosal injury and complications (T, Jaworski, I. Sarosiek, et al. DD&S, 50:357-65, 2005). Mucin, the major component of mucus, is continuously released into the lumen, thus by mixing with the luminal content, especially ingested food, may provide a good and effective lubrication facilitating the passage of non-digestible food components for their subsequent evacuation in an effortless fashion. The role of mucin-related lubrication impairment in patients with chronic constipation remains to be explored. We decided, therefore, to test the rate of soluble mucin secretion in patients with chronic constipation and to compare these results with similar data obtained from asymptomatic volunteers. Methods: The study was approved by IRB and conducted in 17 patients (14F, mean age of 40, 19-64 age range) with symptoms of chronic constipation (CC) diagnosed acc. to Rome III criteria and 16 normal controls (12F, mean age of 42, 19-71 range). The rate of soluble mucin secretion was assessed in aspirated gastric juice in basal and stimulated conditions, (1hr) mimicking ingestedfood conditions using 6μg/kg b.wt. s.c. injections of pentagastrin (Cambridge Lab., U.K.). The content of mucin was measured using conventional PAS methodology, testing mucin, also called mucus glycoprotein. The standard curve was based on purified (using ultracentrifugation @280,000g for 48hrs in CsCl gradient) human gastric mucin. Results are presented as Mean ±SEM for soluble mucin (supernatant of the gastric juice; excluding sediment). Statistical analysis was implemented using Σ-Stat Software (SyStat Inc., CA). Results: The rate of soluble mucin secretion in basal conditions in controls was 64% higher than in patients with CC (24 ±4.3 mg/hr vs. 14.6 ±1.9 mg/hr, P<0.05). The rate of soluble mucin secretion during pentagastrin-stimulated conditions in normal controls was 66% higher than in patients with CC (37.4 ±2.7 mg/hr vs. 22.6 ±1.6 mg/hr, P<0.001). Conclusion: 1.The significantly lower rate of soluble mucin secretion in patients with CC than in normal volunteers may reflect a potential impairment in mucin-related lubrication within the alimentary tract. 2. This may potentially contribute to the development of symptoms related to chronic constipation and may open a new therapeutic avenue for these patients population.