Wen-Di Shen1, Xu Lin2, Hui-Min Liu1, Bo-Yang Li1, Xiang Qiu1, Wan-Qiang Lv1, Xue-Zhen Zhu1, Jonathan Greenbaum3, Rui-Ke Liu2, Jie Shen4, Hong-Mei Xiao5, Hong-Wen Deng6. 1. Center for System Biology, Data Sciences, and Reproductive Health, School of Basic Medical Science, Central South University, 172 Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, PR China. 2. Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, China. 3. Tulane Center of Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University School of Medicine, Tulane University, New Orleans, LA, 70112, USA. 4. Shunde Hospital of Southern Medical University (The First People's Hospital of Shunde), No.1 of Jiazi Road, Lunjiao, Shunde District, Foshan, 528300, Guangdong, China. 5. Center for System Biology, Data Sciences, and Reproductive Health, School of Basic Medical Science, Central South University, 172 Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, PR China. hmxiao@csu.edu.cn. 6. Tulane Center of Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University School of Medicine, Tulane University, New Orleans, LA, 70112, USA. hdeng2@tulane.edu.
Abstract
OBJECTIVE: Many animal experiments and epidemiological studies have shown that the gut microbiota (GM) plays an important role in the development of obesity, but the specific biological mechanism involved in the pathogenesis of disease remain unknown. We aimed to examine the relationships and functional mechanisms of GM on obesity in peri- and post-menopausal women. METHODS: We recruited 499 Chinese peri- and post-menopausal women and performed comprehensive analyses of the gut microbiome, targeted metabolomics for short-chain fatty acids in serum, and host whole-genome sequencing by various association analysis methods. RESULTS: Through constrained linear regression analysis, we found that an elevated abundance of Bacteroides fragilis (B. fragilis) was associated with obesity. We also found that serum levels of acetic acid were negatively associated with obesity, and that B. fragilis was negatively associated with serum acetic acid levels by partial Spearman correlation analysis. Mendelian randomization analysis indicated that B. fragilis increases the risk of obesity and may causally down-regulate acetic acid levels. CONCLUSIONS: We found the gut with B. fragilis may accelerate obesity, in part, by suppressing acetic acid levels. Therefore, B. fragilis and acetic acid may represent important therapeutic targets for obesity intervention in peri- and post-menopausal women.
OBJECTIVE: Many animal experiments and epidemiological studies have shown that the gut microbiota (GM) plays an important role in the development of obesity, but the specific biological mechanism involved in the pathogenesis of disease remain unknown. We aimed to examine the relationships and functional mechanisms of GM on obesity in peri- and post-menopausal women. METHODS: We recruited 499 Chinese peri- and post-menopausal women and performed comprehensive analyses of the gut microbiome, targeted metabolomics for short-chain fatty acids in serum, and host whole-genome sequencing by various association analysis methods. RESULTS: Through constrained linear regression analysis, we found that an elevated abundance of Bacteroides fragilis (B. fragilis) was associated with obesity. We also found that serum levels of acetic acid were negatively associated with obesity, and that B. fragilis was negatively associated with serum acetic acid levels by partial Spearman correlation analysis. Mendelian randomization analysis indicated that B. fragilis increases the risk of obesity and may causally down-regulate acetic acid levels. CONCLUSIONS: We found the gut with B. fragilis may accelerate obesity, in part, by suppressing acetic acid levels. Therefore, B. fragilis and acetic acid may represent important therapeutic targets for obesity intervention in peri- and post-menopausal women.
Authors: Peter J Turnbaugh; Ruth E Ley; Michael A Mahowald; Vincent Magrini; Elaine R Mardis; Jeffrey I Gordon Journal: Nature Date: 2006-12-21 Impact factor: 49.962
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