Microbiota-derived lactate accelerates colon epithelial cell turnover in starvation-refed mice
Microbiota-derived lactate accelerates colon epithelial cell turnover in starvation-refed mice
复制标题
DOI：
10.1038/ncomms2668
复制
发表时间：
2013-04-01
影响因子：
16.6
通讯作者：
Dohi, Taeko
中科院分区：
文献类型：
--
作者：
Okada, Toshihiko;Fukuda, Shinji;Dohi, Taeko
经口进食影响肠上皮细胞的形态和功能，维持胃肠道细胞更新。然而，这些过程究竟是如何调节的，特别是在大肠中，仍然不清楚。在这里，我们确定微生物来源的乳酸作为一个主要因素，诱导肠上皮细胞过度增殖的饥饿-refed小鼠。使用溴脱氧尿苷染色，我们表明，结肠上皮细胞营业额逮捕期间12- 36小时的饥饿和增加12-24小时后再喂养。增强的上皮细胞增殖取决于活鼠乳杆菌、乳酸盐产生和膳食纤维含量的增加。在结肠肿瘤发生的模型中，在再喂食期间暴露于致癌物的小鼠比自由喂食的小鼠产生更多的异常隐窝病灶。此外，饥饿致癌物暴露后大大降低了异常隐窝病灶的发生率。我们的研究结果表明，用于再喂养的食物的内容以及致癌物暴露的时间影响小鼠结肠肿瘤发生的发病率。
Oral food intake influences the morphology and function of intestinal epithelial cells and maintains gastrointestinal cell turnover. However, how exactly these processes are regulated, particularly in the large intestine, remains unclear. Here we identify microbiota-derived lactate as a major factor inducing enterocyte hyperproliferation in starvation-refed mice. Using bromodeoxyuridine staining, we show that colonic epithelial cell turnover arrests during a 12-to 36-h period of starvation and increases 12-24 h after refeeding. Enhanced epithelial cell proliferation depends on the increase in live Lactobacillus murinus, lactate production and dietary fibre content. In the model of colon tumorigenesis, mice exposed to a carcinogen during refeeding develop more aberrant crypt foci than mice fed ad libitum. Furthermore, starvation after carcinogen exposure greatly reduced the incidence of aberrant crypt foci. Our results indicate that the content of food used for refeeding as well as the timing of carcinogen exposure influence the incidence of colon tumorigenesis in mice.