| Summary: | 碩士 === 中山醫學大學 === 營養學研究所 === 101 === Objectives. The aim of study was to determine effects of konjac glucomannan (KGM) and inulin oligosaccharide on tumor development, immune function, intestinal ecology and its mechanisms using a colitis-associated colon carcinogenesis mouse model.
Materials and Methods. Six-week-old C57BL/6J male mice were fed control diet (AIN-93G) and initially divided into vehicle control and AOM-DSS groups for 50 days. The AOM-DSS group was administered with a single carcinogen azoxymethane (AOM) (i.p., 10 mg/kg BW) and three cycles of 1-1.5% (w/v) dextran sodium sulfate (DSS) to induce inflammation of the large intestine. After 3 days of recovery period, the AOM-DSS treated mice were divided into control (AIN-93G diet), and fiber-supplemented (KGM 2%, Inulin 2%, and KGM 1% + Inulin 1% w/w) groups. Mice were sacrificed after 9 weeks of dietary intervention. The severity of adenocarcinoma, leukocyte phagocytic capacity, spleen proinflammatory cytokines, Cox-2 stain, gene expression of cyclin D1 and B-cell lymphoma 2 (bcl-2) in the distal colon, the cecal short-chain fatty acid and fecal microbiota were determined.
Results. Colonic adenocarcinoma occurred in all AOM-DSS-treated mice. Supplementation of konjac and inulin effectively reduced the extent of tumor invasion. Compared to vehicle group, leukocyte phagocytotic ability were lower and spleen interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α)levels were higher in the control group, which was partially reversed with KGM and inulin supplementation. In agreement with that, Cox-2 stain and the gene expression of cyclin D1 were also the most pronounced in the control group among the AOM-DSS induced groups. AOM-DSS treatment jeopardized the fecal bacteria profile and decreased the cecal short-chain fatty acid concentrations. The KGM and inulin supplement increased Bifidobacterium spp. and reduced Clostridium spp. concentration, and effectively increased the cecal short-chain fatty acid concentrations.
Conclusion. This study suggested that supplementation of KGM and inulin (2% w/w diet in mouse, equivalent to 10 g/d in men) during the cancer promotion period could reduce the progression of colitis-associated colon carcinogenesis. The mechanisms mediating effects of these fibers may involve in the improvement of colonic ecology which ultimately reduced the cytokine-induced inflammation and proliferation-related gene expression in the distal colon.
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