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Gut Microbiome Alterations in Pulmonary Hypertension in Highlanders and Lowlanders

Wenxue Dong, Lifeng Ma, Qiumin Huang, Xu Yang, Zhendong Mei, Mengmeng Kong, Zhonghan Sun, Zhiying Zhang, Jing Li, Jiaojiao Zou, Dandan Chen, Yuxiang Dai, Daxin Zhou, Yan Zheng, Longli Kang
ERJ Open Research 2023; DOI: 10.1183/23120541.00617-2022
Wenxue Dong
1Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, China
5These authors contributed equally
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Lifeng Ma
1Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, China
5These authors contributed equally
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Qiumin Huang
2State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
5These authors contributed equally
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  • ORCID record for Qiumin Huang
Xu Yang
1Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, China
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Zhendong Mei
2State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
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Mengmeng Kong
2State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
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Zhonghan Sun
2State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
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Zhiying Zhang
1Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, China
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Jing Li
1Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, China
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Jiaojiao Zou
2State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
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Dandan Chen
3Department of Cardiology, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai, China
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Yuxiang Dai
3Department of Cardiology, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai, China
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Daxin Zhou
3Department of Cardiology, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai, China
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Yan Zheng
2State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
3Department of Cardiology, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai, China
4Yiwu Research Institute of Fudan University, Shanghai, China
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Longli Kang
1Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, China
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Abstract

Background Alterations in the gut microbiota have been observed in patients with pulmonary hypertension (PH), though whether the roles of the gut microbiota in PH at different altitudes are the same is unknown. This study aims to evaluate the associations of the gut microbiome with PH in the highlanders and lowlanders.

Methods PH patients and controls were recruited from those who permanently live on the Tibetan plateau (highlanders) or the plains (lowlanders), and underwent transthoracic echocardiography close to their altitude of residence (at 5070 m for highlanders versus6 m for lowlanders). The gut microbiome was profiled using metagenomic shotgun sequencing.

Results In total, 13 PH patients (46% highlanders) and 88 controls (70% highlanders) were included. The overall microbial composition was different in PH patients compared to controls (p=0.003). Notably, among lowlanders, a composite microbial score of pro-atherosclerotic trimethylamine-producing species was increased in PH patients compared with that in controls (p=0.028), while among highlanders no such difference was observed (p=0.087). Another composite gut microbial score including eight species of Lactobacillus, which has shown beneficial effects on cardiovascular functions, was higher in highlanders than lowlanders (p<0.01). Furthermore, this score tended to be lower in PH patients than controls among highlanders (p=0.056) but not among lowlanders (p=0.840). In addition, the gut microbiome showed a good performance in distinguishing PH patients from controls in both lowlanders and highlanders.

Conclusions Our study reported differently altered gut microbiome profiles between highland and lowland PH patients, highlighting the distinct microbial mechanism in PH between highlanders and lowlanders.

Footnotes

This manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.

Conflict of interest: None.

This is a PDF-only article. Please click on the PDF link above to read it.

  • Received November 16, 2022.
  • Accepted February 15, 2023.
  • Copyright ©The authors 2023
http://creativecommons.org/licenses/by-nc/4.0/

This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions{at}ersnet.org

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Gut Microbiome Alterations in Pulmonary Hypertension in Highlanders and Lowlanders
Wenxue Dong, Lifeng Ma, Qiumin Huang, Xu Yang, Zhendong Mei, Mengmeng Kong, Zhonghan Sun, Zhiying Zhang, Jing Li, Jiaojiao Zou, Dandan Chen, Yuxiang Dai, Daxin Zhou, Yan Zheng, Longli Kang
ERJ Open Research Jan 2023, 00617-2022; DOI: 10.1183/23120541.00617-2022

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Gut Microbiome Alterations in Pulmonary Hypertension in Highlanders and Lowlanders
Wenxue Dong, Lifeng Ma, Qiumin Huang, Xu Yang, Zhendong Mei, Mengmeng Kong, Zhonghan Sun, Zhiying Zhang, Jing Li, Jiaojiao Zou, Dandan Chen, Yuxiang Dai, Daxin Zhou, Yan Zheng, Longli Kang
ERJ Open Research Jan 2023, 00617-2022; DOI: 10.1183/23120541.00617-2022
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