Hypoxia induces senescence of bone marrow mesenchymal stem cells via altered gut microbiota

Junyue Xing, Yongquan Ying, Chenxi Mao, Yiwei Liu, Tingting Wang, Qian Zhao, Xiaoling Zhang, Fuxia Yan and Hao Zhang ()
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Junyue Xing: Chinese Academy of Medical Sciences and Peking Union Medical College
Yongquan Ying: Taizhou Hospital
Chenxi Mao: 1st Affiliated Hospital of Wenzhou Medical University
Yiwei Liu: Chinese Academy of Medical Sciences and Peking Union Medical College
Tingting Wang: Chinese Academy of Medical Sciences and Peking Union Medical College
Qian Zhao: Chinese Academy of Medical Sciences and Peking Union Medical College
Xiaoling Zhang: Chinese Academy of Medical Sciences and Peking Union Medical College
Fuxia Yan: CAMS&PUMC
Hao Zhang: Chinese Academy of Medical Sciences and Peking Union Medical College

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract Systemic chronic hypoxia is a feature of many diseases and may influence the communication between bone marrow (BM) and gut microbiota. Here we analyse patients with cyanotic congenital heart disease (CCHD) who are experiencing chronic hypoxia and characterize the association between bone marrow mesenchymal stem cells (BMSCs) and gut microbiome under systemic hypoxia. We observe premature senescence of BMSCs and abnormal d-galactose accumulation in patients with CCHD. The hypoxia that these patients experience results in an altered diversity of gut microbial communities, with a remarkable decrease in the number of Lactobacilli and a noticeable reduction in the amount of enzyme-degraded d-galactose. Replenishing chronic hypoxic rats with Lactobacillus reduced the accumulation of d-galactose and restored the deficient BMSCs. Together, our findings show that chronic hypoxia predisposes BMSCs to premature senescence, which may be due to gut dysbiosis and thus induced d-galactose accumulation.

Date: 2018
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DOI: 10.1038/s41467-018-04453-9

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