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Anti-inflammatory effects of newly synthesized ?-galacto-oligosaccharides on dextran sulfate sodium-induced colitis in C57BL/6J mice.

ABSTRACT: ?-Galacto-oligosaccharides have been reported to have beneficial health effects. The purpose of this study was to investigate the preventive effects of a newly synthesized ?-galacto-oligosaccharide mixture (?-GOSg), as well as raffinose family oligosaccharides (RFOs), on dextran sulfate sodium (DSS)-induced colitis in mice. When administered in drinking water at 0.5% for 15?days, both ?-GOSg and RFOs significantly decreased fecal hemoglobin content, partially prevented colon length shortening, reduced the severity of colon inflammation, and attenuated DSS-induced upregulation of cyclooxygenase-2. In addition, the activation of the inflammatory regulator nuclear factor-kappa B was slightly inhibited by ?-GOSg. The results showed that the newly synthesized ?-GOSg preparation has similar anti-inflammatory activities as RFOs in this colitis model. The anti-inflammatory activity of ?-GOSg in humans remains to be investigated.

SUBMITTER: Dai Z

PROVIDER: S-EPMC5976246 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Anti-inflammatory effects of newly synthesized α-galacto-oligosaccharides on dextran sulfate sodium-induced colitis in C57BL/6J mice.

Dai Zhuqing Z Feng Simin S Liu Anna A Wang Hong H Zeng Xiaoxiong X Yang Chung S CS

Food research international (Ottawa, Ont.) 20180424

α-Galacto-oligosaccharides have been reported to have beneficial health effects. The purpose of this study was to investigate the preventive effects of a newly synthesized α-galacto-oligosaccharide mixture (α-GOSg), as well as raffinose family oligosaccharides (RFOs), on dextran sulfate sodium (DSS)-induced colitis in mice. When administered in drinking water at 0.5% for 15 days, both α-GOSg and RFOs significantly decreased fecal hemoglobin content, partially prevented colon length shortening, r ...[more]

PMID: 29803460

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Project description:BackgroundG protein-coupled receptor 35 (GPR35) is an orphan receptor and is vastly expressed in immune cells and gastrointestinal cells, suggesting the potential physiological importance of GPR35 in these cells. Here, we tested the hypothesis that the lack of GPR35 expression in the colon mucosa exacerbates the severity of dextran sulfate sodium (DSS)-induced experimental colitis in mice.MethodsColitis was induced in GPR35 wild-type (GPR35+/+) and GPR35 knockout (GPR35-/-) mice through the administration of DSS in drinking water for 5 days followed by regular facility water for 1 day. Induction of colitis was evaluated by measuring relative body weight loss, clinical illness scores, and morphological changes in the colon. Abolition of Gpr35 gene expression in the colon mucosa of GPR35-/- mice was confirmed by quantitative real-time PCR (qPCR). Gene expressions of inflammatory and tissue remodeling cytokines were detected by qPCR. Human colorectal epithelial Caco cells were transfected with siRNA against GPR35 before treated with 1% DSS in vitro. Protein expressions were measured using Western blot.ResultsGPR35-/- mice receiving DSS showed a significantly worsened colitis disease with profound loss of body weight and a considerable amount of severe clinical illness compared to GPR35+/+ mice that received DSS. The histology of colon sections from GPR35-/- mice showed extensive pathological changes including submucosal edema, diffuse ulcerations, and evidence of complete loss of crypts compared to wild-type mice. The mean histopathological score was significantly higher in GPR35-/- mice as compared to GPR35+/+ mice. The qPCR data revealed significant expression of pro-inflammatory and tissue remodeling cytokines in GPR35-/- colon mucosa, including IL-1β, CXCL1, CXCL2, CCL2, HMGB1, TGFβ1, TGFβ3, MMP1/9/12. The protein expressions of Zonula occludens-1, E-cadherin, Claudin1 were decreased upon knocking down GPR35 with or without 1% DSS treatment.ConclusionsOur experimental data suggest that lack of GPR35 resulted in worsened disease outcome in DSS-induced experimental colitis, indicating that GPR35 could play a crucial role in protecting from colonic inflammation and serve as a therapeutic target.

Dataset Information

Anti-inflammatory effects of newly synthesized ?-galacto-oligosaccharides on dextran sulfate sodium-induced colitis in C57BL/6J mice.

Publications

Anti-inflammatory effects of newly synthesized α-galacto-oligosaccharides on dextran sulfate sodium-induced colitis in C57BL/6J mice.

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