Inter-species transplantation of gut microbiota from human to pigs

Inter-species transplantation of gut microbiota from human to pigs
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DOI:
10.1038/ismej.2007.23
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发表时间:
2007-06-01
期刊:
影响因子:
11
通讯作者:
Zhao, Liping
Zhao, Liping
中科院分区:
环境科学与生态学1区
文献类型:
--
作者:
Pang, Xiaoyan;Hua, Xiuguo;Zhao, Liping

文献摘要

被引文献

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由于肠道菌群的巨大多样性和宿主特异性以及伦理问题,直接研究肠道菌群以了解其作为人类个体中“重要器官”的作用是困难的。将人类肠道菌群移植到替代宿主中可以显著促进人类肠道生态、代谢和免疫的研究,但基于啮齿动物的模型提供的结果与人类的相关性较低。利用猪与人在消化系统解剖、生理和代谢方面的高度相似性,建立了一种新的人菌群相关(HFA)仔猪模型。通过剖腹产将仔猪送入SPF级屏障系统中,并经口接种来自一名健康10岁男孩的全粪便混悬液。采用肠细菌重复基因间一致序列-PCR指纹图谱法、群体特异性PCR-温度梯度凝胶电泳和实时荧光定量PCR技术,对HFA仔猪肠道菌群的建立和组成进行了分析,并与人类供体进行了比较。分子分析表明,从人到无菌仔猪的肠道微生物群移植产生了具有最小个体差异的供体样微生物群落。这些前无菌仔猪的微生物演替也与在人类中观察到的相似。该模型为人类代谢、营养和药物发现中的肠道生态学研究提供了一个显著改进的系统。
Direct research on gut microbiota for understanding its role as 'an important organ' in human individuals is difficult owing to its vast diversity and host specificity as well as ethical concerns. Transplantation of human gut microbiota into surrogate hosts can significantly facilitate the research of human gut ecology, metabolism and immunity but rodents-based model provides results with low relevance to humans. A new human flora-associated ( HFA) piglet model was hereby established taking advantage of the high similarity between pigs and humans with respect to the anatomy, physiology and metabolism of the digestive system. Piglets were delivered via cesarean section into a SPF-level barrier system and were inoculated orally with a whole fecal suspension from one healthy 10-year-old boy. The establishment and composition of the intestinal microbiota of the HFA piglets were analyzed and compared with that of the human donor using enterobacterial repetitive intergenic consensus sequence-PCR fingerprinting-based community DNA hybridization, group-specific PCR-temperature gradient gel electrophoresis and real-time PCR. Molecular profiling demonstrated that transplantation of gut microbiota from a human to germfree piglets produced a donor-like microbial community with minimal individual variation. And the microbial succession with aging of those ex-germfree piglets was also similar to that observed in humans. This HFA model provides a significantly improved system for research on gut ecology in human metabolism, nutrition and drug discovery.