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

doi:10.1183/23120541.00617-2022

Gut microbiome alterations in pulmonary hypertension in highlanders and lowlanders

ERJ Open Res. 2023 Jun 26;9(3):00617-2022. doi: 10.1183/23120541.00617-2022. eCollection 2023 May.

Authors

Wenxue Dong^{1

2}, Lifeng Ma^{1

2}, Qiumin Huang^{3

2}, Xu Yang¹, Zhendong Mei³, Mengmeng Kong³, Zhonghan Sun³, Zhiying Zhang¹, Jing Li¹, Jiaojiao Zou³, Dandan Chen⁴, Yuxiang Dai⁴, Daxin Zhou⁴, Yan Zheng^{3

4

5}, Longli Kang¹

Affiliations

¹ Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, China.
² These authors contributed equally.
³ State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China.
⁴ Department of Cardiology, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai, China.
⁵ Yiwu Research Institute of Fudan University, Shanghai, China.

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 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 in highlanders compared with lowlanders.