Higashimura Yasuki, Naito Yuji, Takagi Tomohisa, Uchiyama Kazuhiko, Mizushima Katsura, Ushiroda Chihiro, Ohnogi Hiromu, Kudo Yoko, Yasui Madoka, Inui Seina, Hisada Takayoshi, Honda Akira, Matsuzaki Yasushi, Yoshikawa Toshikazu
Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Food Factor Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan;
Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan;
Am J Physiol Gastrointest Liver Physiol. 2016 Mar 15;310(6):G367-75. doi: 10.1152/ajpgi.00324.2015. Epub 2016 Jan 14.
High-fat diet (HFD)-induced alteration in the gut microbial composition, known as dysbiosis, is increasingly recognized as a major risk factor for various diseases, including colon cancer. This report describes a comprehensive investigation of the effect of agaro-oligosaccharides (AGO) on HFD-induced gut dysbiosis, including alterations in short-chain fatty acid contents and bile acid metabolism in mice. C57BL/6N mice were fed a control diet or HFD, with or without AGO. Terminal restriction fragment-length polymorphism (T-RFLP) analysis produced their fecal microbiota profiles. Profiles of cecal organic acids and serum bile acids were determined, respectively, using HPLC and liquid chromatography-tandem mass spectrometry systems. T-RFLP analyses showed that an HFD changed the gut microbiota significantly. Changes in the microbiota composition induced by an HFD were characterized by a decrease in the order Lactobacillales and by an increase in the Clostridium subcluster XIVa. These changes of the microbiota community generated by HFD treatment were suppressed by AGO supplementation. As supported by the data of the proportion of Lactobacillales order, the concentration of lactic acid increased in the HFD + AGO group. Data from the serum bile acid profile showed that the level of deoxycholic acid, a carcinogenic secondary bile acid produced by gut bacteria, was increased in HFD-receiving mice. The upregulation tended to be suppressed by AGO supplementation. Finally, results show that AGO supplementation suppressed the azoxymethane-induced generation of aberrant crypt foci in the colon derived from HFD-treated mice. Our results suggest that oral intake of AGO prevents HFD-induced gut dysbiosis, thereby inhibiting colon carcinogenesis.
高脂饮食（HFD）引起的肠道微生物组成改变，即生态失调，越来越被认为是包括结肠癌在内的各种疾病的主要危险因素。本报告描述了对琼脂寡糖（AGO）对HFD诱导的肠道生态失调影响的全面研究，包括小鼠短链脂肪酸含量和胆汁酸代谢的变化。将C57BL/6N小鼠喂食对照饮食或HFD，添加或不添加AGO。采用末端限制性片段长度多态性（T-RFLP）分析产生它们的粪便微生物群谱。分别使用高效液相色谱法和液相色谱-串联质谱系统测定盲肠有机酸和血清胆汁酸谱。T-RFLP分析表明，HFD显著改变了肠道微生物群。HFD诱导的微生物群组成变化的特征是乳杆菌目减少，梭菌属 XIVa 亚群增加。AGO 补充剂抑制了 HFD 处理引起的微生物群落的这些变化。如乳杆菌目比例数据所示，HFD + AGO 组中乳酸浓度增加。血清胆汁酸谱数据表明，接受HFD的小鼠中，由肠道细菌产生的致癌二级胆汁酸脱氧胆酸水平升高。AGO补充剂倾向于抑制这种上调。最后，结果表明，AGO补充剂抑制了由HFD处理的小鼠结肠中由氧化偶氮甲烷诱导的异常隐窝灶的产生。我们的结果表明，口服AGO可预防HFD诱导的肠道生态失调，从而抑制结肠癌的发生。
