Pan Zhiyuan, Hu Yichen, Huang Zongyu, Han Ni, Li Yan, Zhuang Xiaomei, Yin Jiye, Peng Hui, Gao Quansheng, Zhang Wenpeng, Huang Yong, Cui Yujun, Bi Yujing, Xu Zhenjiang Zech, Yang Ruifu
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330047, China.
Sci China Life Sci. 2022 Oct;65(10):2093-2113. doi: 10.1007/s11427-021-2056-1. Epub 2022 Mar 14.
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.
肠道微生物群参与宿主对高海拔的反应。然而，肠道微生态的动态变化及其与高原相关疾病的关联仍知之甚少。在此，我们使用低压缺氧挑战大鼠模型模拟高原暴露，并在28天内监测肠道微生物组、短链脂肪酸（SCFAs）和胆汁酸（BAs）。我们发现缺氧大鼠出现体重减轻、红细胞增多症和病理性心脏肥大，同时肠道微生物群发生了巨大的组成变化，这主要由普雷沃氏菌科、卟啉单胞菌科和链球菌科驱动。异常的肠道微生物群的特征是副拟杆菌属、艾利斯杆菌属和乳球菌属的丰度增加，以及拟杆菌与普雷沃氏菌的比例更大。多组学分析表明，肠道微生物组与粪便中SCFAs和BAs的代谢异常显著相关，这表明低压缺氧挑战后微生物组-代谢组的相互作用网络发生了重塑。有趣的是，粪便微生物群移植显著增加了肠道微生物群的多样性，部分抑制了拟杆菌属和艾利斯杆菌属丰度的增加，恢复了血浆丙酸盐的降低，并适度改善了缺氧大鼠的心脏肥大。我们的结果为低压缺氧挑战期间肠道微生态的纵向变化提供了见解。肠道微生物群和微生物代谢产物的异常促成了大鼠高原性心脏病的发展。
