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Abstract
The gut microbiome is an important determinant in various diseases. Here we perform a cross-sectional study of Japanese adults and identify the Blautia genus, especially B. wexlerae, as a commensal bacterium that is inversely correlated with obesity and type 2 diabetes mellitus. Oral administration of B. wexlerae to mice induce metabolic changes and anti-inflammatory effects that decrease both high-fat diet–induced obesity and diabetes. The beneficial effects of B. wexlerae are correlated with unique amino-acid metabolism to produce S-adenosylmethionine, acetylcholine, and l-ornithine and carbohydrate metabolism resulting in the accumulation of amylopectin and production of succinate, lactate, and acetate, with simultaneous modification of the gut bacterial composition. These findings reveal unique regulatory pathways of host and microbial metabolism that may provide novel strategies in preventive and therapeutic approaches for metabolic disorders.
Here, the authors inversely associate Blautia wexlerae with obesity and type 2 diabetes mellitus in humans and further show that administration of B. wexlerae to mice decrease both high-fat diet–induced obesity and diabetes via modulating gut microbial metabolism.
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1 National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, Ibaraki, Japan (GRID:grid.482562.f); National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Laboratory of Gut Environmental System, Collaborative Research Center for Health and Medicine, Ibaraki, Japan (GRID:grid.482562.f)
2 National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, Ibaraki, Japan (GRID:grid.482562.f); Noster Inc., Muko, Japan (GRID:grid.482562.f)
3 National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Laboratory of In-silico Drug Design, Artificial Intelligence Center for Health and Biomedical Research, Ibaraki, Japan (GRID:grid.482562.f)
4 National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Department of Physical Activity Research, Shinjuku, Japan (GRID:grid.482562.f); Ritsumeikan University, Faculty of Sport and Health Science, Kusatsu, Japan (GRID:grid.262576.2) (ISNI:0000 0000 8863 9909)
5 Waseda University, Research Organization for Nano and Life Innovation, Shinjuku, Japan (GRID:grid.5290.e) (ISNI:0000 0004 1936 9975)
6 National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, Ibaraki, Japan (GRID:grid.482562.f)
7 National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Department of Physical Activity Research, Shinjuku, Japan (GRID:grid.482562.f); Toyo University, Faculty of Food and Nutritional Sciences, Oura, Japan (GRID:grid.265125.7) (ISNI:0000 0004 1762 8507)
8 National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Department of Physical Activity Research, Shinjuku, Japan (GRID:grid.482562.f); Kiryu University, Department of Nutrition, Midori, Japan (GRID:grid.448781.6) (ISNI:0000 0004 0638 7154)
9 National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Department of Physical Activity Research, Shinjuku, Japan (GRID:grid.482562.f); Waseda University, Faculty of Sport Sciences, Tokorozawa, Japan (GRID:grid.5290.e) (ISNI:0000 0004 1936 9975)
10 National Institutes of Biomedical Innovation Health and Nutrition (NIBIOHN), Laboratory of Bioinformatics, Artificial Intelligence Center for Health and Biomedical Research, Ibaraki, Japan (GRID:grid.482562.f)
11 National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, Ibaraki, Japan (GRID:grid.482562.f); Osaka University, Graduate School of Pharmaceutical Sciences, Suita, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971)
12 Waseda University, Research Organization for Nano and Life Innovation, Shinjuku, Japan (GRID:grid.5290.e) (ISNI:0000 0004 1936 9975); Waseda University, Department of Life Science and Medical Bioscience, Shinjuku, Japan (GRID:grid.5290.e) (ISNI:0000 0004 1936 9975); AIST-Waseda University, Computational Bio Big-Data Open Innovation Laboratory, Shinjuku, Japan (GRID:grid.5290.e) (ISNI:0000 0004 1936 9975); Waseda Research Institute for Science and Engineering, Institute for Advanced Research of Biosystem Dynamics, Shinjuku, Japan (GRID:grid.5290.e) (ISNI:0000 0004 1936 9975)
13 Shunan City Shinnanyo Hospital, Shunan, Japan (GRID:grid.5290.e)
14 National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Laboratory of In-silico Drug Design, Artificial Intelligence Center for Health and Biomedical Research, Ibaraki, Japan (GRID:grid.482562.f); Osaka University, Institute for Protein Research, Suita, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971)
15 National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, Ibaraki, Japan (GRID:grid.482562.f); National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Laboratory of Gut Environmental System, Collaborative Research Center for Health and Medicine, Ibaraki, Japan (GRID:grid.482562.f); Waseda University, Research Organization for Nano and Life Innovation, Shinjuku, Japan (GRID:grid.5290.e) (ISNI:0000 0004 1936 9975); Osaka University, Graduate School of Pharmaceutical Sciences, Suita, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971); University of Tokyo, International Vaccine Design Center, Institute of Medical Science, Minato, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); Osaka University, Graduate School of Medicine, Suita, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971); Osaka University, Graduate School of Dentistry, Suita, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971); Kobe University, Department of Microbiology and Immunology, Graduate School of Medicine, Kobe, Japan (GRID:grid.31432.37) (ISNI:0000 0001 1092 3077); Osaka University, Graduate School of Science, Toyonaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971)