Chu-Wen Ling1, Zelei Miao2, Mian-Li Xiao1, Hongwei Zhou3,4, Zengliang Jiang2,5, Yuanqing Fu2,5, Feng Xiong1, Luo-Shi-Yuan Zuo1, Yu-Ping Liu1, Yan-Yan Wu1, Li-Peng Jing1, Hong-Li Dong1, Geng-Dong Chen1, Ding Ding1, Cheng Wang1, Fang-Fang Zeng1, Hui-Lian Zhu6, Yan He3, Ju-Sheng Zheng2,5,7, Yu-Ming Chen1. 1. Guangdong Provincial Key Laboratory of Food, Nutrition and Health; Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China. 2. Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China. 3. Microbiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China. 4. State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China. 5. Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, China. 6. Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China. 7. MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Abstract
CONTEXT: Several small studies have suggested that the gut microbiome might influence osteoporosis, but there is little evidence from human metabolomics studies to explain this association. OBJECTIVE: This study examined the association of gut microbiome dysbiosis with osteoporosis and explored the potential pathways through which this association occurs using fecal and serum metabolomics. METHODS: We analyzed the composition of the gut microbiota by 16S rRNA profiling and bone mineral density using dual-energy X-ray absorptiometry in 1776 community-based adults. Targeted metabolomics in feces (15 categories) and serum (12 categories) were further analyzed in 971 participants using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. RESULTS: This study showed that osteoporosis was related to the beta diversity, taxonomy, and functional composition of the gut microbiota. The relative abundance of Actinobacillus, Blautia, Oscillospira, Bacteroides, and Phascolarctobacterium was positively associated with osteoporosis. However, Veillonellaceae other, Collinsella, and Ruminococcaceae other were inversely associated with the presence of osteoporosis. The association between microbiota biomarkers and osteoporosis was related to levels of peptidases and transcription machinery in microbial function. Fecal and serum metabolomics analyses suggested that tyrosine and tryptophan metabolism and valine, leucine, and isoleucine degradation were significantly linked to the identified microbiota biomarkers and to osteoporosis, respectively. CONCLUSION: This large population-based study provided robust evidence connecting gut dysbiosis, fecal metabolomics, and serum metabolomics with osteoporosis. Our results suggest that gut dysbiosis and amino acid metabolism could be targets for intervention in osteoporosis.
CONTEXT: Several small studies have suggested that the gut microbiome might influence osteoporosis, but there is little evidence from human metabolomics studies to explain this association. OBJECTIVE: This study examined the association of gut microbiome dysbiosis with osteoporosis and explored the potential pathways through which this association occurs using fecal and serum metabolomics. METHODS: We analyzed the composition of the gut microbiota by 16S rRNA profiling and bone mineral density using dual-energy X-ray absorptiometry in 1776 community-based adults. Targeted metabolomics in feces (15 categories) and serum (12 categories) were further analyzed in 971 participants using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. RESULTS: This study showed that osteoporosis was related to the beta diversity, taxonomy, and functional composition of the gut microbiota. The relative abundance of Actinobacillus, Blautia, Oscillospira, Bacteroides, and Phascolarctobacterium was positively associated with osteoporosis. However, Veillonellaceae other, Collinsella, and Ruminococcaceae other were inversely associated with the presence of osteoporosis. The association between microbiota biomarkers and osteoporosis was related to levels of peptidases and transcription machinery in microbial function. Fecal and serum metabolomics analyses suggested that tyrosine and tryptophan metabolism and valine, leucine, and isoleucine degradation were significantly linked to the identified microbiota biomarkers and to osteoporosis, respectively. CONCLUSION: This large population-based study provided robust evidence connecting gut dysbiosis, fecal metabolomics, and serum metabolomics with osteoporosis. Our results suggest that gut dysbiosis and amino acid metabolism could be targets for intervention in osteoporosis.