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Gut microbiota remodeling reverses aging-associated inflammation and dysregulation of systemic bile acid homeostasis in mice sex-specifically.

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机构: [a]Functional Metabolomic and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China [b]Human Metabolomics Institute, Inc, Shenzhen, Guangdong, China [c]Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA, USA [d]Department of Endocrinology, Shanghai Fifth People’s Hospital Affiliated to Fudan University, Shanghai, China [e]Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Affiliated Cent Hospital Huzhou University, Huzhou, China [f]Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, China [g]Department of Phytochemistry, College of Pharmacy, Second Military Medical University, Shanghai, China [h]Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China [i]Hong Kong Traditional Chinese Medicine Phenome Research Centre, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China
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关键词: Aging inflammation gut microbiota bile acid composition sex difference

摘要:
Aging is usually characterized with inflammation and disordered bile acids (BAs) homeostasis, as well as gut dysbiosis. The pathophysiological changes during aging are also sexual specific. However, it remains unclear about the modulating process among gut microbiota, BA metabolism, and inflammation during aging. In this study, we established a direct link between gut microbiota and BA profile changes in the liver, serum, and four intestinal segments of both sexes during aging and gut microbiota remodeling by co-housing old mice with young ones. We found aging reduced Actinobacteria in male mice but increased Firmicutes in female mice. Among the top 10 altered genera with aging, 4 genera changed oppositely between male and female mice, and most of the changes were reversed by co-housing in both sexes. Gut microbiota remodeling by co-housing partly rescued the systemically dysregulated BA homeostasis induced by aging in a sex- and tissue-specific manner. Aging had greater impacts on hepatic BA profile in females, but intestinal BA profile in males. In addition, aging increased hepatic and colonic deoxycholic acid in male mice, but reduced them in females. Moreover, muricholic acids shifted markedly in the intestine, especially in old male mice, and partially reversed by co-housing. Notably, the ratios of primary to secondary BAs in the liver, serum, and all four intestinal segments were increased in old mice and reduced by co-housing in both sexes. Together, the presented data revealed that sex divergent changes of gut microbiota and BA profile in multiple body compartments during aging and gut microbiota remodeling, highlighting the sex-specific prevention and treatment of aging-related disorders by targeting gut microbiota-regulated BA metabolism should particularly be given more attention.

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出版当年[2019]版:
大类 | 1 区 医学
小类 | 1 区 微生物学 2 区 胃肠肝病学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 微生物学 2 区 胃肠肝病学
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出版当年[2018]版:
Q1 MICROBIOLOGY Q1 GASTROENTEROLOGY & HEPATOLOGY
最新[2023]版:
Q1 GASTROENTEROLOGY & HEPATOLOGY Q1 MICROBIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2018版] 出版当年五年平均 出版前一年[2017版] 出版后一年[2019版]

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第一作者机构: [a]Functional Metabolomic and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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通讯机构: [a]Functional Metabolomic and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China [h]Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China [i]Hong Kong Traditional Chinese Medicine Phenome Research Centre, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China [*1]Functional Metabolomic and Gut Microbiome Laboratory, Institute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China [*2]Functional Metabolomic and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China [*3]Chinese Medicine Clinical Study Center, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China
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