Cornell Institute of Host-Microbe Interactions and Disease, Department of Entomology, Cornell University, 129 Garden Avenue, Ithaca, NY 14853, USA.
Cornell Institute of Host-Microbe Interactions and Disease, Department of Entomology, Cornell University, 129 Garden Avenue, Ithaca, NY 14853, USA.
Cell Rep. 2022 Mar 29;38(13):110572. doi: 10.1016/j.celrep.2022.110572.
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.
肠道微生物在宿主生理学中发挥着重要作用；然而，其影响的机制仍知之甚少。在这里，我们证明了微生物不仅影响肠道生理学，还改变其上皮细胞组成。微生物群和病原体都影响肠道干细胞（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）命运，并使 EE 在中肠上皮中长期积累。重要的是，进化上保守的果蝇 NFKB（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 通路通过响应感染损伤促进 EE 命运。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、上皮细胞组成和肠道生理学。
