(original) (raw)

TY - JOUR AU - Okada, Toshihiko AU - Fukuda, Shinji AU - Hase, Koji AU - Nishiumi, Shin AU - Izumi, Yoshihiro AU - Yoshida, Masaru AU - Hagiwara, Teruki AU - Kawashima, Rei AU - Yamazaki, Motomi AU - Oshio, Tomoyuki AU - Otsubo, Takeshi AU - Inagaki-Ohara, Kyoko AU - Kakimoto, Kazuki AU - Higuchi, Kazuhide AU - Kawamura, Yuki I. AU - Ohno, Hiroshi AU - Dohi, Taeko PY - 2013 DA - 2013/04/03 TI - Microbiota-derived lactate accelerates colon epithelial cell turnover in starvation-refed mice JO - Nature Communications SP - 1654 VL - 4 IS - 1 AB - 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. SN - 2041-1723 UR - https://doi.org/10.1038/ncomms2668 DO - 10.1038/ncomms2668 ID - Okada2013 ER -