The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites.
The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites.
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DOI：
10.1016/j.cell.2016.05.018
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发表时间：
2016-06-16
期刊：
影响因子：
64.5
通讯作者：
Stappenbeck TS
中科院分区：
文献类型：
--
作者：
Kaiko GE;Ryu SH;Koues OI;Collins PL;Solnica-Krezel L;Pearce EJ;Pearce EL;Oltz EM;Stappenbeck TS
在哺乳动物的肠中，Leiberkühn隐窝在其基部容纳肠上皮干/祖细胞。哺乳动物的肠道还含有多种微生物代谢物化合物，这些化合物可能调节干/祖细胞活性。无偏筛选确定丁酸盐，一个突出的细菌代谢产物，作为一个有效的抑制剂，肠干/祖细胞增殖在生理浓度。在稳态期间，分化的结肠细胞代谢丁酸盐，可能阻止其到达隐窝内的增殖上皮干/祖细胞。通过粘膜损伤或应用于天然无隐窝的宿主生物体，将干/祖细胞在体内暴露于丁酸盐导致增殖抑制和伤口修复延迟。丁酸盐的作用机制依赖于转录因子Foxo 3。我们的研究结果表明，哺乳动物隐窝结构保护干/祖细胞增殖部分通过代谢屏障形成的分化的结肠细胞消耗丁酸，并刺激宿主解剖和微生物代谢的相互作用的未来研究。
In the mammalian intestine, crypts of Leiberkühn house intestinal epithelial stem/progenitor cells at their base. The mammalian intestine also harbors a diverse array of microbial metabolite compounds that potentially modulate stem/progenitor cell activity. Unbiased screening identified butyrate, a prominent bacterial metabolite, as a potent inhibitor of intestinal stem/progenitor proliferation at physiologic concentrations. During homeostasis, differentiated colonocytes metabolized butyrate likely preventing it from reaching proliferating epithelial stem/progenitor cells within the crypt. Exposure of stem/progenitor cells in vivo to butyrate through either mucosal injury or application to a naturally crypt-less host organism led to inhibition of proliferation and delayed wound repair. The mechanism of butyrate action depended on the transcription factor Foxo3. Our findings indicate that mammalian crypt architecture protects stem/progenitor cell proliferation in part through a metabolic barrier formed by differentiated colonocytes that consume butyrate, and stimulate future studies on the interplay of host anatomy and microbiome metabolism.
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