Microbes affect gut epithelial cell composition through immune-dependent regulation of intestinal stem cell differentiation.
Microbes affect gut epithelial cell composition through immune-dependent regulation of intestinal stem cell differentiation.
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微生物通过免疫依赖性调节肠干细胞分化影响肠上皮细胞组成。
DOI：
10.1016/j.celrep.2022.110572
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发表时间：
2022-03-29
期刊：
影响因子：
8.8
通讯作者：
Buchon, Nicolas
中科院分区：
文献类型：
--
作者：
Liu, Xi;Nagy, Peter;Bonfini, Alessandro;Houtz, Philip;Bing, Xiao-Li;Yang, Xiaowei;Buchon, Nicolas
肠道微生物在宿主生理学中发挥着重要作用;然而，其影响的机制仍然很差。在这里，我们证明了微生物不仅影响肠道生理学，而且改变其上皮组成。微生物和病原体都影响肠干细胞（ISC）的分化。有趣的是，虽然微生物群促进ISC分化为肠上皮细胞（EC），但病原体刺激肠内分泌细胞（EE）的命运和EE在中肠上皮细胞中的长期积累。重要的是，进化上保守的果蝇NF κ B（Relish）通过直接调节分化因子将干细胞谱系特化推向EC。相反，JAK-STAT途径促进EE命运响应感染性损伤。我们提出了一个模型，其中微生物模式识别途径，如IMD-Relish和损伤反应途径，如JAK-STAT的平衡影响ISC分化，上皮组成和肠道生理学。Liu等人发现肠道微生物影响肠干细胞分化，从而改变上皮细胞的组成。所有微生物都会刺激Imd/Relish途径（NF-κB），但病原体还会产生刺激JAK-STAT途径的应激和损伤，导致肠内分泌细胞的积累。
Gut microbes play important roles in host physiology; however, the mechanisms underlying their impact remain poorly characterized. Here, we demonstrate that microbes not only influence gut physiology but also alter its epithelial composition. The microbiota and pathogens both influence intestinal stem cell (ISC) differentiation. Intriguingly, while the microbiota promotes ISC differentiation into enterocytes (EC), pathogens stimulate enteroendocrine cell (EE) fate and long-term accumulation of EEs in the midgut epithelium. Importantly, the evolutionarily conserved Drosophila NFKB (Relish) pushes stem cell lineage specification toward ECs by directly regulating differentiation factors. Conversely, the JAK-STAT pathway promotes EE fate in response to infectious damage. We propose a model in which the balance of microbial pattern recognition pathways, such as Imd-Relish, and damage response pathways, such as JAK-STAT, influence ISC differentiation, epithelial composition, and gut physiology. Liu et al. find that gut microbes impact intestinal stem cell differentiation, thus changing epithelial composition. All microbes stimulate the Imd/Relish pathway (NF-κB), but pathogens additionally generate stress and damage that stimulate the JAK-STAT pathway, leading to accumulation of enteroendocrine cells.
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