The gut microbiota is composed of numerous commensal microorganisms. TI40PropionateIntestineAllergicairway inflammationAccumulating evidence has indicated that the gut microbiota deeply im-pact host physiology and pathology. We have been studying this by applying an integrated omics approach, where exhaustive analyses at different layers of or-ganismal activities are combined, namely (meta)genomics, epigenomics, (meta)transcriptomics and metabolomics. Gut microbial metabolites often mediate the microbiota impact on host physiopathology.Obesity and type 2 diabetes are prevalent problems worldwide, not only medically but also socially and economically. Studying human cohorts in com-bination with mouse models, including germ-free and gnotobiotic mice, we have shown that elevated levels of gut microbial elaidic acid and monosaccha-rides in the colon contribute to the pathogenesis of obesity and insulin resis-tance. Therefore, the relatively simple colonic lavage procedure could promote research on the human mucosal microbiota, especially in gastrointestinal disor-ders.We have also shown that gut microbial propionate in the newborn period is involved inpreventing the subsequent onset of bronchial asthma. With a human birth cohort, we first found that the fecal propionate level was lower at 1 month of age in the group of children who were later diagnosed with bronchial asthma at 5 years of age than in the non-asthmatic group. We then turned to a mouse model, where propionate was added to the drinking water of mothers raising newborn pups until weaning. Weaned offspring were then subjected to a house dust mite-induced airway inflammation model at several weeks of age, reveal-ing that the propionate treatment significantly prevented the airway inflamma-tion compared to the untreated water control group. Thus, these gut microbial metabolites can be promising targets for preventive/therapeutic strategies.Figure: Schematic overview of how microbial propionate in the newborn gut prevents sub-sequent allergic airway inflammation in the preschool age infantsHigher propionate levels in the gut during the newborn period are associated with prevention of subsequent bronchial asthma in the preschool age infants. Consis-tently, in the house dust mite-induced allergic airway inflammation model in mice, pups raised by mothers given propionate in the drinking water were protected from subsequent airway inflammation at several weeks of age. Gut and lung eosinophils highly express a propionate receptor GPR41 and propionate treatment upregulates Toll-like receptor (Tlr) genes in these cells, suggesting that the TLR upregulation in eosinophils could be involved in the preventive effects of propionate on airway inflamma-tion (reproduced from a RIKEN press release introducing Ito T, et al. Gut Microbes 15, 2206507 (2023))Recent Major PublicationsTakeuchi T, Kubota T, Nakanishi Y, Tsugawa H, Suda W, Kwon AT, Yazaki J, Ikeda K, Nemoto S, Mochizuki Y, Kitami T, Yugi K, Mizuno Y, Yamamichi N, Yamazaki T, Takamoto I, Kubota N, Kadowaki T, Arner E, Carninci P, Ohara O, Arita M, Hattori M, Koyasu S, Ohno H. Gut microbial carbohydrate metabolism contributes to insulin resistance. Nature 621, 389-395 (2023)Ito T, Nakanishi Y, Shibata R, Sato N, Jinnohara T, Suzuki S, Suda W, Hattori M, Kimura I, Nakano T, Yamaide F, Shimojo N, Ohno H. The propionate-GPR41 axis in infancy protects from subsequent bronchial asthma onset. Gut Microbes 15, 2206507 (2023)Takeuchi T, Kameyama K, Miyauchi E, Nakanishi Y, Kanaya T, Fujii T, Kato T, Sasaki T, Tachibana N, Negishi H, Matsui M, Ohno H. Fatty acid overproduction by gut commensal microbiota exacerbates obesity. Cell Metab 35, 361-375.e9 (2023)Invited presentationsOhno H. “Gut Microbiota, host health and diseases” Institutional Seminar, Institute of Biomedical Sciences, Academia Sinica (Taipei, Taiwan) November 2023Ohno H. “Impact of Gut Microbiome on Obesity and Diabetic Disorders” International Life Sciences Institute Taiwan (ILSI Taiwan) Symposium - Application of Multi-omics on Probiotic, Prebiotic and Postbiotic Studies: Safety, Functionality and Precision Health - (Taipei, Tai-wan) October 2023Ohno H. “Gut microbial metabolites short-chain fatty ac-ids, host defense and immune system” Finnish-Japanese Immunology Symposium: Emerging concepts in im-munology -From basic mechanisms to treating immune mediated diseases (Turku, Finland) August 2023Ohno H. “Gut microbial metabolites in immunity and host defense” The 31st Pillar 2: Forefront of innovative medical approach - Novel view of health and medicine from the standpoint of gut microbiota (Tokyo, Japan) April 2023Ohno H. “Gut microbiota and host pathophysiology” The 57th Research Society for Pseudomonas infection (Tsu-kuba, Japan) January 2023Laboratory for Intestinal EcosystemTeam Leader: Hiroshi Ohno
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