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李洪哲, 李楠, 王晶晶, 李恒, 黄星, 郭磊, 郑惠文, 和占龙, 赵远, 杨泽宁, 范海涛, 储曼曼, 杨谨溪, 吴琼雯, 刘龙丁. 2020: 恒河猴肠道共生菌群失调对小肠形态和机体免疫调节的影响. 动物学研究, 41(1): 20-31. DOI: 10.24272/j.issn.2095-8137.2020.004
引用本文: 李洪哲, 李楠, 王晶晶, 李恒, 黄星, 郭磊, 郑惠文, 和占龙, 赵远, 杨泽宁, 范海涛, 储曼曼, 杨谨溪, 吴琼雯, 刘龙丁. 2020: 恒河猴肠道共生菌群失调对小肠形态和机体免疫调节的影响. 动物学研究, 41(1): 20-31. DOI: 10.24272/j.issn.2095-8137.2020.004
Hong-Zhe Li, Nan Li, Jing-Jing Wang, Heng Li, Xing Huang, Lei Guo, Hui-Wen Zheng, Zhan-Long He, Yuan Zhao, Ze-Ning Yang, Hai-Tao Fan, Man-Man Chu, Jin-Xi Yang, Qiong-Wen Wu, Long-Ding Liu. 2020: Dysbiosis of gut microbiome affecting small intestine morphology and immune balance: a rhesus macaque model. Zoological Research, 41(1): 20-31. DOI: 10.24272/j.issn.2095-8137.2020.004
Citation: Hong-Zhe Li, Nan Li, Jing-Jing Wang, Heng Li, Xing Huang, Lei Guo, Hui-Wen Zheng, Zhan-Long He, Yuan Zhao, Ze-Ning Yang, Hai-Tao Fan, Man-Man Chu, Jin-Xi Yang, Qiong-Wen Wu, Long-Ding Liu. 2020: Dysbiosis of gut microbiome affecting small intestine morphology and immune balance: a rhesus macaque model. Zoological Research, 41(1): 20-31. DOI: 10.24272/j.issn.2095-8137.2020.004

恒河猴肠道共生菌群失调对小肠形态和机体免疫调节的影响

Dysbiosis of gut microbiome affecting small intestine morphology and immune balance: a rhesus macaque model

  • 摘要: 随着测序技术的发展,越来越多的研究表明肠道共生菌群在机体健康和疾病中扮演着重要角色。目前对肠道共生菌群在宿主粘膜表面的作用的认识多源自临床研究分析和小鼠动物研究,然而在小动物模型中,微生物群落和宿主之间作用机制的研究结果有很大的应用局限性。在本研究中,我们证实短期口服广谱抗生素的恒河猴可以作为动物模型来研究肠道共生菌群-宿主-免疫调节之间的关系,并且机体能够维持稳定的健康状态。结果表明,抗生素处理后恒河猴肠道共生菌群的多样性和丰富度显著下降;16S rDNA扩增子测序结果分析表明,用药9天后恒河猴粪便中的优势菌种转变为大肠杆菌和志贺氏菌,且菌群的功能基因和预测KEGG通路的丰度谱也随之发生了显著变化。此外,恒河猴肠道共生菌群的缺失导致小肠黏膜表面上皮细胞出现变性、坏死和脱落等病理改变,还引起机体外周血单个核细胞(PBMCs)中的CD3+T、CD4+T和CD16+NK细胞比例升高,而调节性T细胞和CD20+B细胞的比例下降。PBMCs转录组结果也表明,肠道共生菌群缺失后机体的免疫平衡受到了多种免疫相关基因表达水平的调控,包括IL-13、VCAM1和LGR4等。

     

    Abstract: There is a growing appreciation for the specific health benefits conferred by commensal microbiota on their hosts. Clinical microbiota analysis and animal studies in germ-free or antibiotic-treated mice have been crucial for improving our understanding of the role of the microbiome on the host mucosal surface; however, studies on the mechanisms involved in microbiome-host interactions remain limited to small animal models. Here, we demonstrated that rhesus monkeys under short-term broad-spectrum antibiotic treatment could be used as a model to study the gut mucosal host-microbiome niche and immune balance with steady health status. Results showed that the diversity and community structure of the gut commensal bacteria in rhesus monkeys were both disrupted after antibiotic treatment. Furthermore, the 16S rDNA amplicon sequencing results indicated that Escherichia-Shigella were predominant in stool samples 9 d of treatment, and the abundances of bacterial functional genes and predicted KEGG pathways were significantly changed. In addition to inducing aberrant morphology of small intestinal villi, the depletion of gut commensal bacteria led to increased proportions of CD3+ T, CD4+ T, and CD16+ NK cells in peripheral blood mononuclear cells (PBMCs), but decreased numbers of Treg and CD20+ B cells. The transcriptome of PBMCs from antibiotic-treated monkeys showed that the immune balance was affected by modulation of the expression of many functional genes, including IL-13, VCAM1, and LGR4.

     

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