title: Microbiota-derived lactate accelerates colon epithelial cell turnover in starvation-refed mice.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Okada
authors.forename: Shinji
authors.initials: S
authors.lastname: Fukuda
authors.forename: Koji
authors.initials: K
authors.lastname: Hase
authors.forename: Shin
authors.initials: S
authors.lastname: Nishiumi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Izumi
authors.forename: Masaru
authors.initials: M
authors.lastname: Yoshida
authors.forename: Teruki
authors.initials: T
authors.lastname: Hagiwara
authors.forename: Rei
authors.initials: R
authors.lastname: Kawashima
authors.forename: Motomi
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Oshio
authors.forename: Takeshi
authors.initials: T
authors.lastname: Otsubo
authors.forename: Kyoko
authors.initials: K
authors.lastname: Inagaki-Ohara
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kakimoto
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Higuchi
authors.forename: Yuki I
authors.initials: YI
authors.lastname: Kawamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohno
authors.forename: Taeko
authors.initials: T
authors.lastname: Dohi
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005502:Food; D007413:Intestinal Mucosa / Q000166:cytology* / Q000382:microbiology; D007773:Lactates / Q000378:metabolism*; D007778:Lactobacillus / Q000378:metabolism*; D051379:Mice; D013217:Starvation
chemical_list: D007773:Lactates
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