Gut microbial carbohydrate metabolism contributes to insulin resistance.

Autor: Takeuchi T; Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan., Kubota T; Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan. kubota@oha.toho-u.ac.jp.; Intestinal Microbiota Project, Kanagawa Institute of Industrial Science and Technology, Kawasaki, Japan. kubota@oha.toho-u.ac.jp.; Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. kubota@oha.toho-u.ac.jp.; Division of Diabetes and Metabolism, The Institute for Medical Science Asahi Life Foundation, Tokyo, Japan. kubota@oha.toho-u.ac.jp.; Department of Clinical Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Tokyo, Japan. kubota@oha.toho-u.ac.jp., Nakanishi Y; Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.; Intestinal Microbiota Project, Kanagawa Institute of Industrial Science and Technology, Kawasaki, Japan., Tsugawa H; Metabolome Informatics Research Team, RIKEN Center for Sustainable Resource Science (CSRS), Yokohama, Japan.; Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.; Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.; Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Tokyo, Japan., Suda W; Laboratory for Microbiome Sciences, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan., Kwon AT; Laboratory for Applied Regulatory Genomics Network Analysis, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan., Yazaki J; Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan., Ikeda K; Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.; Department of Applied Genomics, Kazusa DNA Research Institute, Kisarazu, Japan., Nemoto S; Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan., Mochizuki Y; Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan., Kitami T; Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan., Yugi K; Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.; Institute for Advanced Biosciences, Keio University, Fujisawa, Japan.; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan., Mizuno Y; Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.; Development Bank of Japan, Tokyo, Japan., Yamamichi N; Center for Epidemiology and Preventive Medicine, The University of Tokyo Hospital, Tokyo, Japan., Yamazaki T; International University of Health and Welfare, Tokyo, Japan., Takamoto I; Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.; Department of Metabolism and Endocrinology, Tokyo Medical University Ibaraki Medical Center, Ami Town, Japan., Kubota N; Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Kadowaki T; Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.; Toranomon Hospital, Tokyo, Japan., Arner E; Laboratory for Applied Regulatory Genomics Network Analysis, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan., Carninci P; Laboratory for Transcriptome Technology, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.; Fondazione Human Technopole, Milan, Italy., Ohara O; Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.; Department of Applied Genomics, Kazusa DNA Research Institute, Kisarazu, Japan., Arita M; Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.; Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.; Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, Japan.; Human Biology-Microbiome-Quantum Research Center (WPI-Bio2Q), Keio University, Tokyo, Japan., Hattori M; Laboratory for Microbiome Sciences, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan., Koyasu S; Laboratory for Immune Cell Systems, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan., Ohno H; Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan. hiroshi.ohno@riken.jp.; Intestinal Microbiota Project, Kanagawa Institute of Industrial Science and Technology, Kawasaki, Japan. hiroshi.ohno@riken.jp.; Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan. hiroshi.ohno@riken.jp.
Jazyk: angličtina
Zdroj: Nature [Nature] 2023 Sep; Vol. 621 (7978), pp. 389-395. Date of Electronic Publication: 2023 Aug 30.
DOI: 10.1038/s41586-023-06466-x
Abstrakt: Insulin resistance is the primary pathophysiology underlying metabolic syndrome and type 2 diabetes 1,2 . Previous metagenomic studies have described the characteristics of gut microbiota and their roles in metabolizing major nutrients in insulin resistance 3-9 . In particular, carbohydrate metabolism of commensals has been proposed to contribute up to 10% of the host's overall energy extraction 10 , thereby playing a role in the pathogenesis of obesity and prediabetes 3,4,6 . Nevertheless, the underlying mechanism remains unclear. Here we investigate this relationship using a comprehensive multi-omics strategy in humans. We combine unbiased faecal metabolomics with metagenomics, host metabolomics and transcriptomics data to profile the involvement of the microbiome in insulin resistance. These data reveal that faecal carbohydrates, particularly host-accessible monosaccharides, are increased in individuals with insulin resistance and are associated with microbial carbohydrate metabolisms and host inflammatory cytokines. We identify gut bacteria associated with insulin resistance and insulin sensitivity that show a distinct pattern of carbohydrate metabolism, and demonstrate that insulin-sensitivity-associated bacteria ameliorate host phenotypes of insulin resistance in a mouse model. Our study, which provides a comprehensive view of the host-microorganism relationships in insulin resistance, reveals the impact of carbohydrate metabolism by microbiota, suggesting a potential therapeutic target for ameliorating insulin resistance.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: