Sahlgrenska Center for Cardiovascular and Metabolic Research/Wallenberg Laboratory and Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
Ann Nutr Metab. 2011;58 Suppl 2:44-52. doi: 10.1159/000328042. Epub 2011 Aug 12.
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.
人体肠道中栖息着大量的细菌，这些细菌与人类宿主共同进化，并发挥着多种重要功能，影响着我们的生理机能和新陈代谢。人类在出生时肠道是无菌的，随后会被来自母亲和环境的细菌定植。儿童时期肠道微生物组的复杂性会增加，而成人肠道中的细菌基因数量是人类基因的 150 倍还要多。最近，下一代测序技术的进步和无菌小鼠的机制测试，将肠道微生物组确定为导致肥胖的环境因素之一。无菌小鼠可免受饮食诱导肥胖的影响，而肠道微生物组有助于宿主代谢的潜在机制也开始被阐明。肥胖表型与微生物发酵和能量提取增加有关；然而，其他受微生物调节的机制也同样会促进疾病进展。肠道微生物组对肠肝系统中的宿主基因表达有深远影响，包括参与免疫和代谢的基因。例如，肠道微生物组会影响肠道中分泌蛋白的表达，从而调节外周器官的脂质代谢。此外，肠道微生物组也是促炎分子的来源，这些分子通过先天免疫系统信号传递，增强脂肪组织炎症和巨噬细胞募集。TLRs（Toll 样受体）是先天免疫系统的组成部分，巨噬细胞和上皮细胞均表达 TLRs。巨噬细胞中 TLRs 的激活会严重损害葡萄糖稳态，而肠道中的 TLRs 可能会改变肠道微生物组成，从而对宿主代谢产生深远影响。因此，在生命早期重塑肠道微生物组或其功能，可能对宿主生命后期的代谢有益。
