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Alterations in gut microbiota and metabolites associated with altitude-induced cardiac hypertrophy in rats during hypobaric hypoxia challenge

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Abstract

The gut microbiota is involved in host responses to high altitude. However, the dynamics of intestinal microecology and their association with altitude-related illness are poorly understood. Here, we used a rat model of hypobaric hypoxia challenge to mimic plateau exposure and monitored the gut microbiome, short-chain fatty acids (SCFAs), and bile acids (BAs) over 28 d. We identified weight loss, polycythemia, and pathological cardiac hypertrophy in hypoxic rats, accompanied by a large compositional shift in the gut microbiota, which is mainly driven by the bacterial families of Prevotellaceae, Porphyromonadaceae, and Streptococcaceae. The aberrant gut microbiota was characterized by increased abundance of the Parabacteroides, Alistipes, and Lactococcus genera and a larger Bacteroides to Prevotella ratio. Trans-omics analyses showed that the gut microbiome was significantly correlated with the metabolic abnormalities of SCFAs and BAs in feces, suggesting an interaction network remodeling of the microbiome-metabolome after the hypobaric hypoxia challenge. Interestingly, the transplantation of fecal microbiota significantly increased the diversity of the gut microbiota, partially inhibited the increased abundance of the Bacteroides and Alistipes genera, restored the decrease of plasma propionate, and moderately ameliorated cardiac hypertrophy in hypoxic rats. Our results provide an insight into the longitudinal changes in intestinal microecology during the hypobaric hypoxia challenge. Abnormalities in the gut microbiota and microbial metabolites contribute to the development of high-altitude heart disease in rats.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81790632, 31970863, and 31970088) and the National Key Technology Research and Development Program of the Ministry of Science and Technology of China (2020YFA0509600).

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Authors and Affiliations

  1. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China

    Zhiyuan Pan, Zongyu Huang, Ni Han, Yong Huang, Yujun Cui, Yujing Bi & Ruifu Yang

  2. State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330047, China

    Yichen Hu, Yan Li & Zhenjiang Zech Xu

  3. State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China

    Xiaomei Zhuang, Jiye Yin & Wenpeng Zhang

  4. Tianjin Institute of Environmental & Operational Medicine, Tianjin, 300050, China

    Hui Peng & Quansheng Gao

  5. Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China

    Zhenjiang Zech Xu

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  1. Zhiyuan Pan
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Correspondence to Yujing Bi, Zhenjiang Zech Xu or Ruifu Yang.

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Compliance and ethics The author(s) declare that they have no conflict of interest. All animal procedures were carried out in accordance with the Declaration of the National Institutes of Health Guide and Use of Laboratory Animals and approved by the animal care and use committee of the Beijing Institute of Microbiology and Epidemiology (No. IACUC-DWZX-2017-005).

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Pan, Z., Hu, Y., Huang, Z. et al. Alterations in gut microbiota and metabolites associated with altitude-induced cardiac hypertrophy in rats during hypobaric hypoxia challenge. Sci. China Life Sci. 65, 2093–2113 (2022). https://doi.org/10.1007/s11427-021-2056-1

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