High-altitude exposure decreases bone mineral density and its relationship with gut microbiota: Results from the China multi-ethnic cohort (CMEC) study

• Published in: Environmental research Vol. 215; no. Pt 2; p. 114206
• Main Authors: Zuo, Haojiang, Zheng, Tianli, Wu, Kunpeng, Yang, Tingting, Wang, Lingyao, Nima, Qucuo, Bai, Hua, Dong, Ke, Fan, Ziwei, Huang, Shourui, Luo, Ruocheng, Wu, Jialong, Zhou, Junmin, Xu, Huan, Zhang, Yingcong, Feng, Shiyu, Zeng, Peibin, Xiao, Xiong, Guo, Bing, Wei, Yonglan, Pei, Xiaofang, Zhao, Xing
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.12.2022
• Subjects: Adult; Altitude; Bone Density; Bone mineral density (BMD); Butyric Acid - analysis; Butyric Acid - pharmacology; Fatty Acids, Volatile - analysis; Feces - chemistry; Gastrointestinal Microbiome; High-altitude exposure; Humans; Mediation analysis; Microbiota; Osteoporosis; RNA, Ribosomal, 16S - genetics; Short-chain fatty acids (SCFAs); Osteoporosis; Bone mineral density (BMD); Microbiota; Short-chain fatty acids (SCFAs); Mediation analysis; High-altitude exposure
• ISSN: 0013-9351; 1096-0953
• DOI: 10.1016/j.envres.2022.114206

Geographic altitude is a potent environmental factor for human microbiota and bone mineral density. However, little evidence exists in population-based studies with altitude diversity ranges across more than 3000 m. This study assessed the associations between a wide range of altitudes and bone mineral density, as well as the potential mediating role of microbiota in this relationship. A total of 99,556 participants from the China Multi-Ethnic Cohort (CMEC) study were enrolled. The altitude of each participant was extracted from global Shuttle Radar Topography Mission (SRTM) 4 data. Bone mineral density was measured by calcaneus quantitative ultrasound index (QUI). Stool samples were collected for 16S rRNA gene sequencing (n = 1384). The metabolites of gut microbiota, seven kinds of short-chain fatty acids (SCFAs), were detected by gas chromatography–mass spectrometry (GC-MS, n = 128). After screening, 73,974 participants were selected for the “altitude-QUI” analysis and they were placed into the low-altitude (LA) and high-altitude (HA) groups. Additionally, a subgroup (n = 1384) was further selected for the “altitude-microbiota-QUI” analysis. Multivariate linear regression models and mediation analyses were conducted among participants. A significant negative association between high-altitude and QUI was obtained (mean difference = −0.373 standard deviation [SD], 95% confidence interval [CI]: −0.389, −0.358, n = 73,974). The same negative association was also observed in the population with microbiota data (mean difference = −0.185 SD, 95%CI: −0.360, −0.010, n = 1384), and a significant mediating effect of Catenibacteriumon on the association between altitude and QUI (proportion mediated = 25.2%, P = 0.038) was also noticed. Additionally, the acetic acid, butyric acid, and total amount of seven SCFAs of the low-altitude group were significantly higher than that of the high-altitude group (P < 0.05). High-altitude exposure may decrease bone mineral density in adults, thus increasing the risk of osteoporosis. The modulation of gut microbiota may be a potential strategy for alleviating the decrease of bone mineral density. •A significant negative association between altitude and QUI was found.•The associations were greater among males, older adults, and smokers.•Gut microbiota could be a potential anti-osteoporosis target.