Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells
Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells
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DOI：
10.1073/pnas.202604299
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发表时间：
2002-11-26
影响因子：
11.1
通讯作者：
Gordon, JI
中科院分区：
文献类型：
--
作者：
Stappenbeck, TS;Hooper, LV;Gordon, JI
成年小鼠肠道含有复杂的血管网络。人们对控制该网络发展的因素知之甚少。定量三维成像研究表明，在出生后发育期间，小肠绒毛中形成了分支互连血管丛，这与本土肠道微生物（微生物群）的复杂社会的组装相一致。为了研究这种环境转变对血管发育的影响，我们将无菌小鼠的毛细血管网络与出生后肠道发育期间或完成后定植的前无菌动物的毛细血管网络进行了比较。成年无菌小鼠已阻止毛细血管网络的形成。使用从常规饲养的小鼠中收获的完整微生物群或使用正常小鼠/人类肠道中的主要居民多形拟杆菌定植后，可以在定植后 10 天内重新启动并完成发育程序。肠上皮中的潘氏细胞分泌影响肠腔微生物生态的抗菌肽。对缺乏潘氏细胞的无菌小鼠和多形拟杆菌定植的转基因小鼠的比较表明，微生物对血管生成的调节依赖于这种谱系。这些发现揭示了一种以前未被认识到的出生后动物发育机制，其中定植于粘膜表面的微生物被指定负责通过细菌感应上皮细胞发出信号来调节底层微脉管系统的形成。
The adult mouse intestine contains an intricate vascular network. The factors that control development of this network are poorly understood. Quantitative three-dimensional imaging studies revealed that a plexus of branched interconnected vessels developed in small intestinal villi during the period of postnatal development that coincides with assembly of a complex society of indigenous gut microorganisms (microbiota). To investigate the impact of this environmental transition on vascular development, we compared the capillary networks of germ-free mice with those of ex-germfree animals colonized during or after completion of postnatal gut development. Adult germ-free mice had arrested capillary network formation. The developmental program can be restarted and completed within 10 days after colonization with a complete microbiota harvested from conventionally raised mice, or with Bacteroides thetaiotaomicron, a prominent inhabitant of the normal mouse/human gut. Paneth cells in the intestinal epithelium secrete antibacterial peptides that affect luminal microbial ecology. Comparisons of germ-free and B. thetaiotaomicron-colonized transgenic mice lacking Paneth cells established that microbial regulation of angiogenesis depends on this lineage. These findings reveal a previously unappreciated mechanism of postnatal animal development, where microbes colonizing a mucosal surface are assigned responsibility for regulating elaboration of the underlying microvasculature by signaling through a bacteria-sensing epithelial cell.