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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.

SUBMITTER: Kajiwara-Kubtota M

PROVIDER: S-EPMC10050209 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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

Kajiwara-Kubota Mariko M Uchiyama Kazuhiko K Asaeda Kohei K Kobayashi Reo R Hashimoto Hikaru H Yasuda Takeshi T Sugino Satoshi S Sugaya Takeshi T Hirai Yasuko Y Mizushima Katsura K Doi Toshifumi T Inoue Ken K Dohi Osamu O Yoshida Naohisa N Ishikawa Takeshi T Takagi Tomohisa T Konishi Hideyuki H Inoue Ryo R Itoh Yoshito Y Naito Yuji Y

NPJ science of food 20230328 1

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 investi ...[more]

PMID: 36977699

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Project description:The vital role of naturally occurring dietary fibers (DFs) in maintaining intestinal health has fueled the incorporation of isolated DFs into processed foods. A select group of soluble DFs, such as partially hydrolyzed guar gum (Phgg), are being promoted as dietary supplements to meet recommended DF intake. However, the potential effects of regular consumption of these processed DFs on gastrointestinal health remain largely unknown. The present study assessed the impact of Phgg on the development of intestinal inflammation and colitis-associated colon carcinogenesis (CAC). Wild-type C57BL/6 mice were fed isocaloric diets containing either 7.5% Phgg and 2.5% cellulose (Phgg group) or 10% cellulose (control) for four weeks. To induce colitis, a subgroup of mice from each group was switched to 1.4% dextran sulfate sodium (DSS) in drinking water for seven days. CAC was induced in another subgroup through a single dose of azoxymethane (AOM, 7.5 mg/kg i.p.) followed by three DSS/water cycles. To our surprise, Phgg feeding exacerbated DSS-induced colitis, as evidenced by body weight loss, disrupted colonic crypt architecture, and increased pro-inflammatory markers accompanied by a decrease in anti-inflammatory markers. Additionally, Phgg feeding led to increased colonic expression of genes promoting cell proliferation. Accordingly, extensive colon tumorigenesis was observed in Phgg-fed mice in the AOM/DSS model, whereas the control group exhibited no visible tumors. To investigate whether reducing Phgg has a distinct effect on colitis and CAC development, mice were fed a low-Phgg diet (2.5% Phgg). The low-Phgg group also exhibited increased colitis and tumorigenesis compared to the control, although the severity was markedly lower than in the regular Phgg (7.5%) group, suggesting a dose-dependent effect of Phgg in colitis and CAC development. Our study reveals that Phgg supplementation exacerbates colitis and promotes colon tumorigenesis, warranting further investigation into the potential gastrointestinal health risks associated with processed Phgg consumption.

Dataset Information

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

Publications

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

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