Meta-analysis identifying gut microbial biomarkers of Qinghai-Tibet Plateau populations and the functionality of microbiota-derived butyrate in high-altitude adaptation
Hongwen Zhao,
Longjie Sun,
Jiali Liu,
Bin Shi,
Yaopeng Zhang,
Ci-Ren Qu-Zong,
Tsechoe Dorji,
Tieyu Wang,
Hongli Yuan,
Jinshui Yang
Affiliations
Hongwen Zhao
State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
Longjie Sun
State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
Jiali Liu
State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
Bin Shi
Key Laboratory of Environmental Nanotechnology and Health Effects Research, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China
Yaopeng Zhang
State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
Ci-Ren Qu-Zong
State Key Laboratory of Tibetan Plateau Earth System, Resources and Environment (TPESRE), Institute of Tibetan Plateau Research, Chinese Academy of Sciences, Beijing, China
Tsechoe Dorji
State Key Laboratory of Tibetan Plateau Earth System, Resources and Environment (TPESRE), Institute of Tibetan Plateau Research, Chinese Academy of Sciences, Beijing, China
Tieyu Wang
Guangdong Provincial Key Laboratory of Marine Disaster Prediction and Prevention, Shantou University, Shantou, China
Hongli Yuan
State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
Jinshui Yang
State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
ABSTRACTThe extreme environmental conditions of a plateau seriously threaten human health. The relationship between gut microbiota and human health at high altitudes has been extensively investigated. However, no universal gut microbiota biomarkers have been identified in the plateau population, limiting research into gut microbiota and high-altitude adaptation. 668 16s rRNA samples were analyzed using meta-analysis to reduce batch effects and uncover microbiota biomarkers in the plateau population. Furthermore, the robustness of these biomarkers was validated. Mendelian randomization (MR) results indicated that Tibetan gut microbiota may mediate a reduced erythropoietic response. Functional analysis and qPCR revealed that butyrate may be a functional metabolite in high-altitude adaptation. A high-altitude rat model showed that butyrate reduced intestinal damage caused by high altitudes. According to cell experiments, butyrate may downregulate hypoxia-inducible factor-1α (HIF-1α) expression and blunt cellular responses to hypoxic stress. Our research found universally applicable biomarkers and investigated their potential roles in promoting human health at high altitudes.
