Mucin O-glycans facilitate symbiosynthesis to maintain gut immune homeostasisResearch in context
Background: The dysbiosis of gut microbiota has been implicated in the pathogenesis of inflammatory bowel diseases; however, the underlying mechanisms have not yet been elucidated. Heavily glycosylated mucin establishes a first-line barrier against pathogens and serves as a niche for microbial growt...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-10-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419306061 |
| _version_ | 1818821515832983552 |
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| author | Takahiro Yamada Shingo Hino Hideki Iijima Tomomi Genda Ryo Aoki Ryuji Nagata Kyu-Ho Han Masato Hirota Yusuke Kinashi Hiroyuki Oguchi Wataru Suda Yukihiro Furusawa Yumiko Fujimura Jun Kunisawa Masahira Hattori Michihiro Fukushima Tatsuya Morita Koji Hase |
| author_facet | Takahiro Yamada Shingo Hino Hideki Iijima Tomomi Genda Ryo Aoki Ryuji Nagata Kyu-Ho Han Masato Hirota Yusuke Kinashi Hiroyuki Oguchi Wataru Suda Yukihiro Furusawa Yumiko Fujimura Jun Kunisawa Masahira Hattori Michihiro Fukushima Tatsuya Morita Koji Hase |
| author_sort | Takahiro Yamada |
| collection | DOAJ |
| description | Background: The dysbiosis of gut microbiota has been implicated in the pathogenesis of inflammatory bowel diseases; however, the underlying mechanisms have not yet been elucidated. Heavily glycosylated mucin establishes a first-line barrier against pathogens and serves as a niche for microbial growth. Methods: To elucidate relationships among dysbiosis, abnormal mucin utilisation, and microbial metabolic dysfunction, we analysed short-chain fatty acids (SCFAs) and mucin components in stool samples of 40 healthy subjects, 49 ulcerative colitis (UC) patients, and 44 Crohn's disease (CD) patients from Japan. Findings: Levels of n-butyrate were significantly lower in stools of both CD and UC patients than in stools of healthy subjects. Correlation analysis identified seven bacterial species positively correlated with n-butyrate levels; the major n-butyrate producer, Faecalibacterium prausnitzii, was particularly underrepresented in CD patients, but not in UC patients. In UC patients, there were inverse correlations between mucin O-glycan levels and the production of SCFAs, such as n-butyrate, suggesting that mucin O-glycans serve as an endogenous fermentation substrate for n-butyrate production. Indeed, mucin-fed rodents exhibited enhanced n-butyrate production, leading to the expansion of RORgt+Treg cells and IgA-producing cells in colonic lamina propria. Microbial utilisation of mucin-associated O-glycans was significantly reduced in n-butyrate-deficient UC patients. Interpretation: Mucin O-glycans facilitate symbiosynthesis of n-butyrate by gut microbiota. Abnormal mucin utilisation may lead to reduced n-butyrate production in UC patients. Fund: Japan Society for the Promotion of Science, Health Labour Sciences Research Grant, AMED-Crest, AMED, Yakult Foundation, Keio Gijuku Academic Development Funds, The Aashi Grass Foundation, and The Canon Foundation. Keywords: Microbiota, Butyrate, Mucin, Inflammatory bowel disease |
| first_indexed | 2024-12-18T23:09:25Z |
| format | Article |
| id | doaj.art-1fc34f92344d45ba8b53d2df0d0c350d |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-18T23:09:25Z |
| publishDate | 2019-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-1fc34f92344d45ba8b53d2df0d0c350d2022-12-21T20:48:21ZengElsevierEBioMedicine2352-39642019-10-0148513525Mucin O-glycans facilitate symbiosynthesis to maintain gut immune homeostasisResearch in contextTakahiro Yamada0Shingo Hino1Hideki Iijima2Tomomi Genda3Ryo Aoki4Ryuji Nagata5Kyu-Ho Han6Masato Hirota7Yusuke Kinashi8Hiroyuki Oguchi9Wataru Suda10Yukihiro Furusawa11Yumiko Fujimura12Jun Kunisawa13Masahira Hattori14Michihiro Fukushima15Tatsuya Morita16Koji Hase17Division of Biochemistry, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, JapanDepartment of Applied Biological Chemistry, Graduate School of Agriculture, Shizuoka University, Shizuoka, JapanDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Osaka, JapanDepartment of Applied Biological Chemistry, Graduate School of Agriculture, Shizuoka University, Shizuoka, JapanDivision of Gastroenterology and Hepatology, School of Medicine, Keio University, Shinjuku-ku, Tokyo, JapanDepartment of Food Science, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, JapanDepartment of Food Science, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, JapanDivision of Biochemistry, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, JapanDivision of Biochemistry, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, JapanDivision of Biochemistry, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, JapanGraduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan; Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, JapanDepartment of Liberal Arts and Sciences, Toyama Prefectural University, Toyama, JapanDivision of Biochemistry, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, JapanLaboratory of Vaccine Materials and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan; Department of Microbiology and Immunology, Kobe University Graduate School of Medicine, Hyogo, Japan; Graduate School of Medicine, Graduate School of Pharmaceutical Sciences, Graduate School of Dentistry, Osaka University, Osaka, Japan; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo (IMSUT), Tokyo, JapanGraduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan; Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, JapanDepartment of Food Science, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, JapanDepartment of Applied Biological Chemistry, Graduate School of Agriculture, Shizuoka University, Shizuoka, Japan; Corresponding author.Division of Biochemistry, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, Japan; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo (IMSUT), Tokyo, Japan; Corresponding author at: Division of Biochemistry, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, Japan.Background: The dysbiosis of gut microbiota has been implicated in the pathogenesis of inflammatory bowel diseases; however, the underlying mechanisms have not yet been elucidated. Heavily glycosylated mucin establishes a first-line barrier against pathogens and serves as a niche for microbial growth. Methods: To elucidate relationships among dysbiosis, abnormal mucin utilisation, and microbial metabolic dysfunction, we analysed short-chain fatty acids (SCFAs) and mucin components in stool samples of 40 healthy subjects, 49 ulcerative colitis (UC) patients, and 44 Crohn's disease (CD) patients from Japan. Findings: Levels of n-butyrate were significantly lower in stools of both CD and UC patients than in stools of healthy subjects. Correlation analysis identified seven bacterial species positively correlated with n-butyrate levels; the major n-butyrate producer, Faecalibacterium prausnitzii, was particularly underrepresented in CD patients, but not in UC patients. In UC patients, there were inverse correlations between mucin O-glycan levels and the production of SCFAs, such as n-butyrate, suggesting that mucin O-glycans serve as an endogenous fermentation substrate for n-butyrate production. Indeed, mucin-fed rodents exhibited enhanced n-butyrate production, leading to the expansion of RORgt+Treg cells and IgA-producing cells in colonic lamina propria. Microbial utilisation of mucin-associated O-glycans was significantly reduced in n-butyrate-deficient UC patients. Interpretation: Mucin O-glycans facilitate symbiosynthesis of n-butyrate by gut microbiota. Abnormal mucin utilisation may lead to reduced n-butyrate production in UC patients. Fund: Japan Society for the Promotion of Science, Health Labour Sciences Research Grant, AMED-Crest, AMED, Yakult Foundation, Keio Gijuku Academic Development Funds, The Aashi Grass Foundation, and The Canon Foundation. Keywords: Microbiota, Butyrate, Mucin, Inflammatory bowel diseasehttp://www.sciencedirect.com/science/article/pii/S2352396419306061 |
| spellingShingle | Takahiro Yamada Shingo Hino Hideki Iijima Tomomi Genda Ryo Aoki Ryuji Nagata Kyu-Ho Han Masato Hirota Yusuke Kinashi Hiroyuki Oguchi Wataru Suda Yukihiro Furusawa Yumiko Fujimura Jun Kunisawa Masahira Hattori Michihiro Fukushima Tatsuya Morita Koji Hase Mucin O-glycans facilitate symbiosynthesis to maintain gut immune homeostasisResearch in context EBioMedicine |
| title | Mucin O-glycans facilitate symbiosynthesis to maintain gut immune homeostasisResearch in context |
| title_full | Mucin O-glycans facilitate symbiosynthesis to maintain gut immune homeostasisResearch in context |
| title_fullStr | Mucin O-glycans facilitate symbiosynthesis to maintain gut immune homeostasisResearch in context |
| title_full_unstemmed | Mucin O-glycans facilitate symbiosynthesis to maintain gut immune homeostasisResearch in context |
| title_short | Mucin O-glycans facilitate symbiosynthesis to maintain gut immune homeostasisResearch in context |
| title_sort | mucin o glycans facilitate symbiosynthesis to maintain gut immune homeostasisresearch in context |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419306061 |
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