MSCs Therapy Reverse the Gut Microbiota in Hypoxia-Induced Pulmonary Hypertension Mice

Frontiers in Physiology

Jihong Xu¹  Lingjie Luo³  Zhenxia Zhang³  Deming Gou⁴  Lei Yang⁴  Qinhua Chen⁴ 

[1] Department of Anesthesiology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, China;Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, China;School of Life Sciences and Food Engineering, Hanshan Normal University, Chaozhou, China;Shenzhen Key Laboratory of Microbial Genetic Engineering, Guangdong Provincial Key Laboratory of Regional Immunity and Disease, Vascular Disease Research Center, Carson International Cancer Center, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China;

关键词: pulmonary hypertension;    MSC;    gut microbiota;    biomarker;    vascular;   

DOI  :  10.3389/fphys.2021.712139

来源: DOAJ

【 摘 要 】

Mesenchymal stem cell (MSC) therapy is a promising therapeutic approach based on its strong effect on pulmonary hypertension (PH) in rats. However, the detailed mechanism of MSC therapy remains unknown. Alterations in the gut microbiota were found in both type 1 pulmonary arterial hypertension patients and hypoxia/SU5416- or monocrotaline (MCT)-induced PH rats. However, whether the therapeutic mechanism of MSCs is associated with the gut microbiota is poorly understood. Here, we found that gut microbiota homeostasis was disrupted in hypoxia-induced PH mice due to the increased Firmicutes-to-Bacteroidetes (F/B) ratio; enhanced abundances of harmful Marinifilaceae, Helicobacteraceae, and Lactobacillaceae; and decreased abundances of beneficial Bacteroidaceae, Prevotellaceae, Tannerellaceae, and Lachnospiraceae. Unexpectedly, reverses of the increase in disease-associated microbiota and decrease in anti-inflammatory and immunomodulatory functional microbiota were observed in the MSC-treated group. We also identified harmful Erysipelotrichaceae, Alphaproteobacteria, Christensenella timonensis, Coriobacteriales, and Rhodospirillales that may serve as gut microbiota biomarkers of hypoxia-induced PH mice. Micrococcaales, Nesterenkonia, Anaerotruncus, and Tyzzerella may serve as gut microbiota biomarkers of MSC-treated mice. In summary, MSC treatment suppresses hypoxia-induced pulmonary hypertension in mice, and alterated gut microbiota may play a role in the development and progression of PH. The mechanism of MSC therapy is associated with various metabolic pathways of the gut microbiota in hypoxia model PH mice.

【 授权许可】

Unknown