Gut Microbiota‐Associated Metabolites Affected the Susceptibility to Heart Health Abnormality in Young Migrants at High‐Altitude

ABSTRACT Young migrants, particularly those at high altitudes, are predisposed to heart health abnormalities, including high‐altitude heart disease. Despite the profound impact of hypobaric hypoxia on the gut microbial community, the understanding of the roles played by gut microbiota and gut microb...

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Main Authors: Yongqiang Zhou, Zhexin Ni, Jingjing Liu, Dezhi Sun, Pan Shen, Xi Chen, Gaofu Li, Zhijie Bai, Yangyi Hu, Ningning Wang, Rui Wang, Lina Guan, Yihao Wang, Xianglin Tang, Yungang Lu, Baokun He, Haitao Lu, Wei Zhou, Yue Gao
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Exploration
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Online Access:https://doi.org/10.1002/EXP.20240332
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author Yongqiang Zhou
Zhexin Ni
Jingjing Liu
Dezhi Sun
Pan Shen
Xi Chen
Gaofu Li
Zhijie Bai
Yangyi Hu
Ningning Wang
Rui Wang
Lina Guan
Yihao Wang
Xianglin Tang
Yungang Lu
Baokun He
Haitao Lu
Wei Zhou
Yue Gao
author_facet Yongqiang Zhou
Zhexin Ni
Jingjing Liu
Dezhi Sun
Pan Shen
Xi Chen
Gaofu Li
Zhijie Bai
Yangyi Hu
Ningning Wang
Rui Wang
Lina Guan
Yihao Wang
Xianglin Tang
Yungang Lu
Baokun He
Haitao Lu
Wei Zhou
Yue Gao
author_sort Yongqiang Zhou
collection DOAJ
description ABSTRACT Young migrants, particularly those at high altitudes, are predisposed to heart health abnormalities, including high‐altitude heart disease. Despite the profound impact of hypobaric hypoxia on the gut microbial community, the understanding of the roles played by gut microbiota and gut microbiota‐associated serum metabolites in high‐altitude heart diseases remains limited. Therefore, we conducted a comprehensive multi‐omics analysis involving 230 graduates from the same university, with 163 Tibetan Plateau migrants and 67 Chengdu Plain residents, and identified 206 differential metabolites (82 in serum and 124 in feces) and 369 species that differed between migrants and residents. Among these, 27 microbial species and four metabolites (Ketoglutaric acid, L‐Aspartic acid, 3‐Guanidinopropionic acid, betaine) detected in both serum and feces were found to be associated with migrants exhibiting compromised heart health, as diagnosed through clinical examinations. Notably, the abundances of Veillonella rogosae and Streptococcus rubneri were correlated with serum levels of L‐Aspartic acid, betaine, and Ketoglutaric acid in heart health‐abnormal individuals. Validation of these microbiome biomarkers and gut microbiota‐associated serum metabolites in an independent cohort demonstrated their excellent predictive ability for indicating heart health abnormalities in migrants (AUC = 0.7857). Furthermore, supplementation with these identified species or gut microbiota‐associated serum metabolites effectively mitigated hypobaric hypoxia‐induced increases in serum lactate, glycolysis, myocardial damage, and cardiac hypertrophy. Integrated analysis revealed that the alterations in the gut microbiome negatively regulated key metabolic pathways such as the malate‐aspartate shuttle, tricarboxylic acid cycle, and oxidative phosphorylation in heart health‐abnormal individuals. The migration to high‐altitude plateaus significantly reshaped the gut microbiome and metabolome signatures. Lower abundances of Veillonella rogosae, Streptococcus rubneri, and gut microbiota‐associated serum metabolites promoted the remodeling of metabolic processes, thereby increasing susceptibility to high‐altitude heart health abnormalities. Overall, our findings elucidate the microbial mechanisms underlying high‐altitude heart disease and provide valuable insights for potential early intervention strategies in this context.
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spelling doaj-art-fa53fa18bb5a43f682d0b12ada99919a2025-08-26T10:32:53ZengWileyExploration2766-85092766-20982025-08-0154n/an/a10.1002/EXP.20240332Gut Microbiota‐Associated Metabolites Affected the Susceptibility to Heart Health Abnormality in Young Migrants at High‐AltitudeYongqiang Zhou0Zhexin Ni1Jingjing Liu2Dezhi Sun3Pan Shen4Xi Chen5Gaofu Li6Zhijie Bai7Yangyi Hu8Ningning Wang9Rui Wang10Lina Guan11Yihao Wang12Xianglin Tang13Yungang Lu14Baokun He15Haitao Lu16Wei Zhou17Yue Gao18Beijing Institute of Radiation MedicineBeijingChinaBeijing Institute of Radiation MedicineBeijingChinaSchool of Chinese MedicineHong Kong Traditional Chinese Medicine Phenome Research CenterState Key Laboratory of Environmental and Biological AnalysisHong Kong Baptist UniversityHong KongChinaBeijing Institute of Radiation MedicineBeijingChinaBeijing Institute of Radiation MedicineBeijingChinaDepartment of Respiratory MedicineArmy 954 HospitalShannan, TibetChinaBeijing Institute of Radiation MedicineBeijingChinaBeijing Institute of Radiation MedicineBeijingChinaBeijing Institute of Radiation MedicineBeijingChinaBeijing Institute of Radiation MedicineBeijingChinaGeneral Hospital of Xinjiang Military CommandUrumqiXinjiangChinaGeneral Hospital of Xinjiang Military CommandUrumqiXinjiangChinaBeijing Institute of Radiation MedicineBeijingChinaBeijing Institute of Radiation MedicineBeijingChinaDepartment of GeneticsThe University of Texas MD Anderson Cancer CenterHoustonTexasUSADepartment of GastroenterologyShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChinaSchool of Chinese MedicineHong Kong Traditional Chinese Medicine Phenome Research CenterState Key Laboratory of Environmental and Biological AnalysisHong Kong Baptist UniversityHong KongChinaBeijing Institute of Radiation MedicineBeijingChinaBeijing Institute of Radiation MedicineBeijingChinaABSTRACT Young migrants, particularly those at high altitudes, are predisposed to heart health abnormalities, including high‐altitude heart disease. Despite the profound impact of hypobaric hypoxia on the gut microbial community, the understanding of the roles played by gut microbiota and gut microbiota‐associated serum metabolites in high‐altitude heart diseases remains limited. Therefore, we conducted a comprehensive multi‐omics analysis involving 230 graduates from the same university, with 163 Tibetan Plateau migrants and 67 Chengdu Plain residents, and identified 206 differential metabolites (82 in serum and 124 in feces) and 369 species that differed between migrants and residents. Among these, 27 microbial species and four metabolites (Ketoglutaric acid, L‐Aspartic acid, 3‐Guanidinopropionic acid, betaine) detected in both serum and feces were found to be associated with migrants exhibiting compromised heart health, as diagnosed through clinical examinations. Notably, the abundances of Veillonella rogosae and Streptococcus rubneri were correlated with serum levels of L‐Aspartic acid, betaine, and Ketoglutaric acid in heart health‐abnormal individuals. Validation of these microbiome biomarkers and gut microbiota‐associated serum metabolites in an independent cohort demonstrated their excellent predictive ability for indicating heart health abnormalities in migrants (AUC = 0.7857). Furthermore, supplementation with these identified species or gut microbiota‐associated serum metabolites effectively mitigated hypobaric hypoxia‐induced increases in serum lactate, glycolysis, myocardial damage, and cardiac hypertrophy. Integrated analysis revealed that the alterations in the gut microbiome negatively regulated key metabolic pathways such as the malate‐aspartate shuttle, tricarboxylic acid cycle, and oxidative phosphorylation in heart health‐abnormal individuals. The migration to high‐altitude plateaus significantly reshaped the gut microbiome and metabolome signatures. Lower abundances of Veillonella rogosae, Streptococcus rubneri, and gut microbiota‐associated serum metabolites promoted the remodeling of metabolic processes, thereby increasing susceptibility to high‐altitude heart health abnormalities. Overall, our findings elucidate the microbial mechanisms underlying high‐altitude heart disease and provide valuable insights for potential early intervention strategies in this context.https://doi.org/10.1002/EXP.20240332glycolysisheart health abnormalitymetabolomicmetagenomicplateau migrants
spellingShingle Yongqiang Zhou
Zhexin Ni
Jingjing Liu
Dezhi Sun
Pan Shen
Xi Chen
Gaofu Li
Zhijie Bai
Yangyi Hu
Ningning Wang
Rui Wang
Lina Guan
Yihao Wang
Xianglin Tang
Yungang Lu
Baokun He
Haitao Lu
Wei Zhou
Yue Gao
Gut Microbiota‐Associated Metabolites Affected the Susceptibility to Heart Health Abnormality in Young Migrants at High‐Altitude
Exploration
glycolysis
heart health abnormality
metabolomic
metagenomic
plateau migrants
title Gut Microbiota‐Associated Metabolites Affected the Susceptibility to Heart Health Abnormality in Young Migrants at High‐Altitude
title_full Gut Microbiota‐Associated Metabolites Affected the Susceptibility to Heart Health Abnormality in Young Migrants at High‐Altitude
title_fullStr Gut Microbiota‐Associated Metabolites Affected the Susceptibility to Heart Health Abnormality in Young Migrants at High‐Altitude
title_full_unstemmed Gut Microbiota‐Associated Metabolites Affected the Susceptibility to Heart Health Abnormality in Young Migrants at High‐Altitude
title_short Gut Microbiota‐Associated Metabolites Affected the Susceptibility to Heart Health Abnormality in Young Migrants at High‐Altitude
title_sort gut microbiota associated metabolites affected the susceptibility to heart health abnormality in young migrants at high altitude
topic glycolysis
heart health abnormality
metabolomic
metagenomic
plateau migrants
url https://doi.org/10.1002/EXP.20240332
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