Programming of Host Metabolism by the Gut Microbiota
Programming of Host Metabolism by the Gut Microbiota
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DOI：
10.1159/000328042
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发表时间：
2011-01-01
影响因子：
3.9
通讯作者：
Backhed, Fredrik
中科院分区：
文献类型：
--
作者：
Backhed, Fredrik
人类肠道内有大量的细菌，它们与人类宿主共同进化，并执行影响我们生理和代谢的几项重要功能。人类肠道在出生时是无菌的，随后被来自母亲和环境的细菌定殖。肠道微生物群的复杂性在儿童时期增加，成年人含有的细菌基因是人类基因的150倍。下一代测序技术和对gnotobiotic小鼠的机制测试的最新进展已经将肠道微生物群确定为导致肥胖的环境因素。无菌小鼠受到保护，免受饮食诱导的肥胖症的影响，肠道微生物群促进宿主代谢的潜在机制开始得到澄清。肥胖表型与微生物发酵和能量提取增加有关;然而，其他微生物调节机制也有助于疾病进展。肠道微生物群对肝肠系统中的宿主基因表达具有深远的影响，包括参与免疫和代谢的基因。例如，肠道微生物群影响肠道中分泌蛋白的表达，其调节外周器官中的脂质代谢。此外，肠道微生物群也是促炎分子的来源，促炎分子通过先天免疫系统的信号传导增加脂肪炎症和巨噬细胞募集。TLR（Toll样受体）是先天免疫系统的组成部分，由巨噬细胞和上皮细胞表达。巨噬细胞中TLR的激活显著损害葡萄糖稳态，而肠道中的TLR可能改变肠道微生物组成，这可能对宿主代谢产生深远影响。因此，在生命早期重新编程肠道微生物群或其功能可能对生命后期的宿主代谢产生有益影响。版权所有（C）2011 S. Karger AG，巴塞尔
The human gut harbors a vast ensemble of bacteria that has co-evolved with the human host and performs several important functions that affect our physiology and metabolism. The human gut is sterile at birth and is subsequently colonized with bacteria from the mother and the environment. The complexity of the gut microbiota is increased during childhood, and adult humans contain 150-fold more bacterial genes than human genes. Recent advances in next-generation sequencing technology and mechanistic testing in gnotobiotic mice have identified the gut microbiota as an environmental factor that contributes to obesity. Germ-free mice are protected against developing diet-induced obesity and the underlying mechanisms whereby the gut microbiota contributes to host metabolism are beginning to be clarified. The obese phenotype is associated with increased microbial fermentation and energy extraction; however, other microbially modulated mechanisms contribute to disease progression as well. The gut microbiota has profound effects on host gene expression in the enterohepatic system, including genes involved in immunity and metabolism. For example, the gut microbiota affects expression of secreted proteins in the gut, which modulate lipid metabolism in peripheral organs. In addition, the gut microbiota is also a source of proinflammatory molecules that augment adipose inflammation and macrophage recruitment by signaling through the innate immune system. TLRs (Toll-like receptors) are integral parts of the innate immune system and are expressed by both macrophages and epithelial cells. Activation of TLRs in macrophages dramatically impairs glucose homeostasis, whereas TLRs in the gut may alter the gut microbial composition that may have profound effects on host metabolism. Accordingly, reprogramming the gut microbiota, or its function, in early life may have beneficial effects on host metabolism later in life. Copyright (C) 2011 S. Karger AG, Basel