Rewiring of Uric Acid Metabolism in the Intestine Promotes High-Altitude Hypoxia Adaptation in Humans.

Autor:	Su Q; Key Laboratory of Genetic Evolution & Animal Models (Chinese Academy of Sciences), Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.; University of Chinese Academy of Sciences, Beijing 100049, China., Li YC; Key Laboratory of Genetic Evolution & Animal Models (Chinese Academy of Sciences), Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China., Zhuang DH; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming, Yunnan 650091, China., Liu XY; Department of Military Medical Geography, Army Health Service Training Base, Army Medical University, Chongqing 400038, China., Gao H; Key Laboratory of Genetic Evolution & Animal Models (Chinese Academy of Sciences), Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China., Li D; College of Life Science, Sichuan Agricultural University, Ya'an, Sichuan 625014, China., Chen Y; Department of Military Medical Geography, Army Health Service Training Base, Army Medical University, Chongqing 400038, China., Ge MX; Key Laboratory of Genetic Evolution & Animal Models (Chinese Academy of Sciences), Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China., Han YM; Key Laboratory of Genetic Evolution & Animal Models (Chinese Academy of Sciences), Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China., Gao ZL; Key Laboratory of Genetic Evolution & Animal Models (Chinese Academy of Sciences), Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China., Yin FQ; Key Laboratory of Genetic Evolution & Animal Models (Chinese Academy of Sciences), Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China., Zhao L; Key Laboratory of Genetic Evolution & Animal Models (Chinese Academy of Sciences), Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China., Zhang YX; The Second Affiliated Hospital, the School of Basic Medicine and Life Sciences, Hainan Medical University, Hainan 570102, China., Yang LQ; Key Laboratory of Genetic Evolution & Animal Models (Chinese Academy of Sciences), Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China., Zhao Q; Hospital of Chengdu Office of People's Government of Tibetan Autonomous Region, Chengdu, Sichuan 610041, China., Luo YJ; Department of Military Medical Geography, Army Health Service Training Base, Army Medical University, Chongqing 400038, China., Zhang Z; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming, Yunnan 650091, China., Kong QP; Key Laboratory of Genetic Evolution & Animal Models (Chinese Academy of Sciences), Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.; CAS Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
Jazyk:	angličtina
Zdroj:	Molecular biology and evolution [Mol Biol Evol] 2024 Nov 01; Vol. 41 (11).
DOI:	10.1093/molbev/msae233
Abstrakt:	Adaptation to high-altitude hypoxia is characterized by systemic and organ-specific metabolic changes. This study investigates whether intestinal metabolic rewiring is a contributing factor to hypoxia adaptation. We conducted a longitudinal analysis over 108 days, with seven time points, examining fecal metabolomic data from a cohort of 46 healthy male adults traveling from Chongqing (a.s.l. 243 m) to Lhasa (a.s.l. 3,658 m) and back. Our findings reveal that short-term hypoxia exposure significantly alters intestinal metabolic pathways, particularly those involving purines, pyrimidines, and amino acids. A notable observation was the significantly reduced level of intestinal uric acid, the end product of purine metabolism, during acclimatization (also called acclimation) and additional two long-term exposed cohorts (Han Chinese and Tibetans) residing in Shigatse, Xizang (a.s.l. 4,700 m), suggesting that low intestinal uric acid levels facilitate adaptation to high-altitude hypoxia. Integrative analyses with gut metagenomic data showed consistent trends in intestinal uric acid levels and the abundance of key uric acid-degrading bacteria, predominantly from the Lachnospiraceae family. The sustained high abundance of these bacteria in the long-term resident cohorts underscores their essential role in maintaining low intestinal uric acid levels. Collectively, these findings suggest that the rewiring of intestinal uric acid metabolism, potentially orchestrated by gut bacteria, is crucial for enhancing human resilience and adaptability in extreme environments. Competing Interests: Conflict of Interests The authors declare that they have no competing interests. (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)
Databáze:	MEDLINE
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