Promotion of Intestinal Epithelial Cell Turnover by Commensal Bacteria: Role of Short-Chain Fatty Acids.
Promotion of Intestinal Epithelial Cell Turnover by Commensal Bacteria: Role of Short-Chain Fatty Acids.
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DOI：
10.1371/journal.pone.0156334
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Matozaki T
中科院分区：
文献类型：
--
作者：
Park JH;Kotani T;Konno T;Setiawan J;Kitamura Y;Imada S;Usui Y;Hatano N;Shinohara M;Saito Y;Murata Y;Matozaki T
肠上皮细胞（IECs）的寿命很短（3-5天），其调节被认为对肠上皮的内稳态很重要。我们现在已经研究了共生菌在小肠内IEC转换调节中的作用。在无菌小鼠和使用混合抗生素治疗的SPF小鼠中，iec在肠隐窝中的增殖活性以及这些细胞沿着隐窝绒毛轴的迁移都明显减弱，其中革兰氏阳性菌选择性抗生素在这方面是最有效的。将SPF小鼠经氯仿处理的粪便口服给无菌小鼠，可显著增加IEC周转率，表明形成孢子的革兰氏阳性菌参与了这一作用。口服短链脂肪酸（SCFAs）作为细菌发酵产物，也恢复了抗生素处理的SPF小鼠iec的周转，并促进了体外肠道类器官的发育。抗生素治疗降低了SPF小鼠IECs中ERK、核糖体蛋白S6和STAT3的磷酸化水平。因此，我们的研究结果表明，革兰氏阳性共生菌是IEC转换的主要决定因素，它们的刺激作用是由scfa介导的。
The life span of intestinal epithelial cells (IECs) is short (3–5 days), and its regulation is thought to be important for homeostasis of the intestinal epithelium. We have now investigated the role of commensal bacteria in regulation of IEC turnover in the small intestine. The proliferative activity of IECs in intestinal crypts as well as the migration of these cells along the crypt-villus axis were markedly attenuated both in germ-free mice and in specific pathogen–free (SPF) mice treated with a mixture of antibiotics, with antibiotics selective for Gram-positive bacteria being most effective in this regard. Oral administration of chloroform-treated feces of SPF mice to germ-free mice resulted in a marked increase in IEC turnover, suggesting that spore-forming Gram-positive bacteria contribute to this effect. Oral administration of short-chain fatty acids (SCFAs) as bacterial fermentation products also restored the turnover of IECs in antibiotic-treated SPF mice as well as promoted the development of intestinal organoids in vitro. Antibiotic treatment reduced the phosphorylation levels of ERK, ribosomal protein S6, and STAT3 in IECs of SPF mice. Our results thus suggest that Gram-positive commensal bacteria are a major determinant of IEC turnover, and that their stimulatory effect is mediated by SCFAs.