title: Protective effect of agaro-oligosaccharides on gut dysbiosis and colon tumorigenesis in high-fat diet-fed mice.
abstract: 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.
authors.affiliation: 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;
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Higashimura
authors.affiliation: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; ynaito@koto.kpu-m.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan;
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Takagi
authors.affiliation: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan;
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Uchiyama
authors.affiliation: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan;
authors.forename: Katsura
authors.initials: K
authors.lastname: Mizushima
authors.affiliation: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan;
authors.forename: Chihiro
authors.initials: C
authors.lastname: Ushiroda
authors.affiliation: Department of Food Factor Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Takara Bio Incorporated, Otsu, Shiga, Japan;
authors.forename: Hiromu
authors.initials: H
authors.lastname: Ohnogi
authors.affiliation: Takara Bio Incorporated, Otsu, Shiga, Japan;
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kudo
authors.affiliation: Takara Bio Incorporated, Otsu, Shiga, Japan;
authors.forename: Madoka
authors.initials: M
authors.lastname: Yasui
authors.affiliation: Takara Bio Incorporated, Otsu, Shiga, Japan;
authors.forename: Seina
authors.initials: S
authors.lastname: Inui
authors.affiliation: TechnoSuruga Laboratory Company Limited, Shizuoka, Japan; and.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Hisada
authors.affiliation: Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Ami, Ibaraki, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Honda
authors.affiliation: Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Ami, Ibaraki, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuzaki
authors.affiliation: Department of Food Factor Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan;
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D003013:Clostridium; D003110:Colonic Neoplasms / Q000382:microbiology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004043:Dietary Fiber; D064806:Dysbiosis / Q000139:chemically induced / Q000382:microbiology*; D004731:Endotoxins / Q000097:blood; D005227:Fatty Acids / Q000378:metabolism; D005243:Feces / Q000382:microbiology; D056546:Lactobacillales; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D009765:Obesity / Q000517:prevention & control; D009844:Oligosaccharides / Q000737:chemistry / Q000494:pharmacology*; D012685:Sepharose / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001647:Bile Acids and Salts; D004043:Dietary Fiber; D004731:Endotoxins; D005227:Fatty Acids; D009844:Oligosaccharides; D012685:Sepharose
keywords: Lactobacillales; colon cancer; deoxycholic acid; gut microbiota; short-chain fatty acid