Partially hydrolyzed guar gum increased colonic mucus layer in mice via succinate-mediated MUC2 production

Abstract

Colonic mucus layers protect intestinal tissues against intestinal bacteria. We investigated the effects of dietary fiber and its metabolites on mucus production in the colonic mucosa. Mice were fed a partially hydrolyzed guar gum (PHGG)-containing diet and a fiber-free diet (FFD). The colon mucus layer, fecal short-chain fatty acid (SCFA) levels, and gut microbiota were evaluated. Mucin 2 (MUC2) expression was assessed in SCFA-treated LS174T cells. The role of AKT in MUC2 production was investigated. The mucus layer in the colonic epithelium was significantly increased in the PHGG group compared with that in the FFD group. In the PHGG group, an increase in Bacteroidetes in the stool was observed, and fecal acetate, butyrate, propionate, and succinate levels were significantly increased. However, MUC2 production was significantly increased only in succinate-stimulated LS174T cells. The succinate-induced MUC2 production was associated with AKT phosphorylation. Succinate mediated the PHGG-induced increase in the colon mucus layer.

Urolithin A-mediated augmentation of intestinal barrier function through elevated secretory mucin synthesis

“…Kajiwara et al found that partially hydrolyzed guar gum (PHGG) administration increased MUC2 production in the mouse intestine. Notably, they also reported that PHGG administration increased the abundance of family S24-7 and SCFA concentration, including propionic acid, in the intestine, consistent with our findings regarding Uro A administration 35 . Propionic acid affects intestinal immune function via the G protein-coupled receptor (GPR)41, and GPR43 inhibits local neutrophil migration in the colon and regulates colonic Treg cell homeostasis 36 , 37 .…”

“…Propionic acid affects intestinal immune function via the G protein-coupled receptor (GPR)41, and GPR43 inhibits local neutrophil migration in the colon and regulates colonic Treg cell homeostasis 36 , 37 . Regarding mucus production, a previous report using the same LS174T cells as our study argued that among SCFAs, succinic acid induces MUC2 expression via the AKT pathway, and propionic acid did not upregulate MUC2 35 . These results suggest that the stimulatory effect of UroA on intestinal mucus secretion does not operate directly via propionic acid produced by gut microbiota.…”

Effectiveness of Partially Hydrolyzed Guar Gum on Cognitive Function and Sleep Efficiency in Healthy Elderly Subjects in a Randomized, Double-Blind, Placebo-Controlled, and Parallel-Group Study

“…Additionally, hormones secreted in the gut due to their promotion by short-chain fatty acids also modulate the central nervous system via systemic circulation or the vagus nerve pathway [ 53 , 54 ]. Indeed, PHGG has been shown to enhance the intestinal barrier function by promoting the production of short-chain fatty acids, thereby increasing mucin and tight junction proteins and inhibiting the influx of inflammatory substances into the body, consequently suppressing internal inflammation [ 29 , 30 , 55 , 56 , 57 , 58 ]. In addition, the results of fecal culture from elderly participants supplemented with PHGG revealed a change in the profile of the fecal microbiota, along with enhanced production of short-chain fatty acids in the fermentation supernatant, and the addition of this fermentation supernatant was found to strengthen the barrier function of inflammation-induced intestinal epithelial model cells [ 59 ].…”

“…It is produced by hydrolyzing the high-viscosity gum extracted from the endosperm of the seeds, making it easily added to food products as a supplement [ 26 ]. Structurally composed of galactomannan, PHGG exhibits high fermentability by intestinal bacteria, which promotes the production of short-chain fatty acids [ 27 , 28 ] and contributes to maintaining the intestinal barrier function [ 29 , 30 ]. Numerous human clinical trials have demonstrated its efficacy in improving bowel movements [ 31 , 32 ] and alleviating diarrhea [ 33 , 34 , 35 ], leading to its widespread use as a prebiotic.…”

Gut Frailty: Its Concept and Pathogenesis

“…Administration of a high-fat diet to animal models, such as mice, results in a thinning of the colonic mucus layer and a reduction in intestinal motility, leading to chronic constipation [ 17 ]. It is known that drugs such as aspirin [ 18 ] and a diet lacking in dietary fiber also decrease intestinal mucus [ 19 ], which has been reported to be associated with increased intestinal permeability and intestinal inflammation. Importantly, the reduction of goblet cells and thinning of the mucus layer have been shown to progress with aging [ 20 ], suggesting a common pathophysiology between age-related intestinal changes and gut frailty.…”