The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice.

The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice.
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DOI:
10.1126/scitranslmed.3000322
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发表时间:
2009-11-11
影响因子:
17.1
通讯作者:
Gordon JI
Gordon JI
中科院分区:
医学1区
文献类型:
--
作者:
Turnbaugh PJ;Ridaura VK;Faith JJ;Rey FE;Knight R;Gordon JI

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饮食和营养状况是人类健康最重要的、可改变的决定因素。食物的营养价值部分受到人的肠道微生物群落(微生物群)及其组成基因(微生物组)的影响。揭示饮食、肠道微生物群的结构和运作以及营养和能量收获之间的相互关系,受到人类环境暴露、微生物生态和基因型变化的影响。为了克服这些问题,我们通过将新鲜或冷冻的成人粪便微生物群落移植到无菌的C57BL/6J小鼠体内,建立了一个定义明确、具有代表性的人类肠道生态系统动物模型。对细菌定植的时间、空间和代际模式进行的培养无关的宏基因组分析表明,这些人源化小鼠的定植稳定且具有遗传性,并复制了供体微生物群的大部分细菌多样性。从低脂肪、富含植物多糖的饮食转变为高脂肪/高糖的“西方”饮食,在一天内改变了微生物群的结构,改变了微生物群代谢途径的表现,并改变了微生物群基因的表达。互惠移植涉及供体和受体饮食的各种组合,表明定殖历史影响微生物群落的初始结构,但这些影响可以通过饮食迅速改变。喂食西方饮食的人源化小鼠肥胖增加;该性状可通过微生物群移植传播。人源化的非生物小鼠将有助于进行原理验证的“临床试验”,以测试环境和遗传因素对肠道微生物群和宿主生理的影响。
Diet and nutritional status are among the most important, modifiable determinants of human health. The nutritional value of food is influenced in part by a person’s gut microbial community (microbiota) and its component genes (microbiome). Unraveling the interrelationships between diet, the structure and operations of the gut microbiota, and nutrient and energy harvest is confounded by variations in human environmental exposures, microbial ecology and genotype. To help overcome these problems, we created a well-defined, representative animal model of the human gut ecosystem by transplanting fresh or frozen adult human fecal microbial communities into germ-free C57BL/6J mice. Culture-independent, metagenomic analysis of the temporal, spatial and intergenerational patterns of bacterial colonization showed that these humanized mice were stably and heritably colonized, and reproduced much of the bacterial diversity of the donor’s microbiota. Switching from a low-fat, plant polysaccharide-rich diet to a high-fat/high-sugar “Western” diet shifted the structure of the microbiota within a single day, changed the representation of metabolic pathways in the microbiome, and altered microbiome gene expression. Reciprocal transplants involving various combinations of donor and recipient diets revealed that colonization history influences the initial structure of the microbial community, but that these effects can be rapidly altered by diet. Humanized mice fed the Western diet have increased adiposity; this trait is transmissible via microbiota transplantation. Humanized gnotobiotic mice will be useful for conducting proof-of-principle “clinical trials” that test the effects of environmental and genetic factors on the gut microbiota and host physiology.
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发表时间: 2009-07-03
期刊: The Journal of biological chemistry
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