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伴侣动物专题研讨会:微生物组的人类化动物模型。

Companion animals symposium: humanized animal models of the microbiome.

机构信息

Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.

出版信息

J Anim Sci. 2011 May;89(5):1531-7. doi: 10.2527/jas.2010-3371. Epub 2010 Sep 10.

Abstract

Humans and other mammals are colonized by trillions of microorganisms, most of which reside in the gastrointestinal tract, that provide key metabolic capabilities, such as the biosynthesis of vitamins and AA, the degradation of dietary plant polysaccharides, and the metabolism of orally administered therapeutics. Although much progress has been made by studying the human microbiome directly, comparing the human microbiome with that of other animals, and constructing in vitro models of the human gut, there remains a need to develop in vivo models where host, microbial, and environmental parameters can be manipulated. Here, we discuss some of the initial results from a promising method that enables the direct manipulation of microbial community structure, environmental exposures, host genotype, and other factors: the colonization of germ-free animals with complex microbial communities, including those from humans or other animal donors. Analyses of these resulting "humanized" gut microbiomes have begun to reveal 1) that key microbial activities can be transferred from the donor to the recipient animal (e.g., microbial reduction of cholesterol and production of equol), 2) that dietary shifts can affect the composition, gene abundance, and gene expression of the gut microbiome, 3) the succession of the microbial community in infants and ex-germ-free adult animals, and 4) the biogeography of these microbes across the length of gastrointestinal tract. Continued studies of humanized and other intentionally colonized animal models stand to provide new insight into not only the human microbiome, but also the microbiomes of our animal companions.

摘要

人类和其他哺乳动物被数万亿微生物定植,其中大部分存在于胃肠道中,这些微生物提供了关键的代谢能力,如维生素和 AA 的生物合成、膳食植物多糖的降解以及口服治疗药物的代谢。虽然通过直接研究人类微生物组、比较人类微生物组与其他动物的微生物组以及构建人类肠道的体外模型已经取得了很大进展,但仍需要开发能够操纵宿主、微生物和环境参数的体内模型。在这里,我们讨论了一种有前途的方法的一些初步结果,该方法能够直接操纵微生物群落结构、环境暴露、宿主基因型和其他因素:用包括人类或其他动物供体来源的复杂微生物群落定植无菌动物。对这些产生的“人源化”肠道微生物组的分析开始揭示出:1)关键微生物活性可以从供体转移到受体动物(例如,胆固醇的微生物还原和雌马酚的产生);2)饮食变化会影响肠道微生物组的组成、基因丰度和基因表达;3)婴儿和前无菌成年动物的微生物群落的演替;4)这些微生物在胃肠道长度上的生物地理学。对人源化和其他有意定植的动物模型的持续研究有望不仅为人类微生物组,也为我们动物伴侣的微生物组提供新的见解。

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