Increased fermentable carbohydrate intake alters colonic mucus barrier function through glycation processes and increased mast cell counts

Abstract

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder for which dietary interventions can be a useful treatment. In recent years, the low‐FODMAP approach is gaining traction in this regard. The fermentation of these non‐absorbed carbohydrates by the gut microbiota can generate toxic glycating metabolites, such as methylglyoxal. These metabolites can have harmful effects by their role in the generation of advanced glycation end products (AGEs), which activates Receptor for AGEs (AGER). Mast cells can be stimulated by AGEs and play a role in IBS. We have treated mice with lactose or fructo‐oligosaccharides (FOS), with or without co‐administration of pyridoxamine and investigated the colonic mucus barrier. We have found that an increased intake of lactose and fructo‐oligosaccharides induces a dysregulation of the colonic mucus barrier, increasing mucus discharge in empty colon, while increasing variability and decreasing average thickness mucus layer covering the fecal pellet. Changes were correlated with increased mast cell counts, pointing to a role for the crosstalk between these and goblet cells. Additionally, AGE levels in colonic epithelium were increased by treatment with the selected fermentable carbohydrates. Observed effects were prevented by co‐treatment with anti‐glycation agent pyridoxamine, implicating glycation processes in the negative impact of fermentable carbohydrate ingestion. This study shows that excessive intake of fermentable carbohydrates can cause colonic mucus barrier dysregulation in mice, by a process that involves glycating agents and increased mucosal mast cell counts.

The Intake of Dicarbonyls and Advanced Glycation Endproducts as Part of the Habitual Diet Is Not Associated with Intestinal Inflammation in Inflammatory Bowel Disease and Irritable Bowel Syndrome Patients

“…Several animal studies have shown that a heat-treated chow diet, high in dietary AGEs, can lead to the gut microbiota composition perturbations [ 5 , 6 , 8 , 68 , 70 , 71 ]. On the other hand, studies with mice on a lactose or fructo-oligosaccharide-diet resulted in an increased colonic epithelial RAGE expression, increased mucosal mast cells numbers and activity, abdominal hypersensitivity [ 72 ], and a dysregulation of the colonic mucus barrier [ 73 ]. As this was accompanied by increased CML levels in the colonic epithelium, and was prevented by co-treatment with pyridoxamine, a known anti-glycation agent, this points towards microbial involvement in glycation processes [ 73 ].…”

“…On the other hand, studies with mice on a lactose or fructo-oligosaccharide-diet resulted in an increased colonic epithelial RAGE expression, increased mucosal mast cells numbers and activity, abdominal hypersensitivity [ 72 ], and a dysregulation of the colonic mucus barrier [ 73 ]. As this was accompanied by increased CML levels in the colonic epithelium, and was prevented by co-treatment with pyridoxamine, a known anti-glycation agent, this points towards microbial involvement in glycation processes [ 73 ]. As the intestinal microbiota displays large inter-individual variation and moreover differences in composition have been shown in IBD and IBS as compared to controls [ 74 ], further studies are needed to study the impact of the endogenous dicarbonyl and AGEs generation and the involvement of the individual’s microbiota composition and activity.…”

A Novel Mast Cell Stabilizer JM25-1 Rehabilitates Impaired Gut Barrier by Targeting the Corticotropin-Releasing Hormone Receptors

“…), which impair the intracellular tight junction (TJ) between the intestinal epithelial cells [ 7 , 10 , 11 ]. CRH receptor subtype 1 (CRHR1) and subtype 2 (CRHR2) on MC are positive and negative modulators, respectively, tuning the degranulation of stress-induced MC [ 12 , 13 ].Psychological stress is a common cause and induces a long-term depressive symptom for IBS, a disorder with an increase of MC and accompanied by intestinal dysbiosis in the gastrointestinal tract [ 14 , 15 , 16 , 17 ]. Certainly, targeting MC is one of the main approaches for dysregulated mucosal permeability [ 5 ].…”

How pain sensors make the gut weep

“…Indeed, feeding of FODMAPs provoked mucus discharge, which was associated with an increased number of mast cells. 8 It however remains to be determined whether mast cells can directly communicate with goblet cells or they provoke mucus secretion indirectly via activation of TRPV1 + nociceptors.…”