Microbiota-derived lactate accelerates colon epithelial cell turnover in starvation-refed mice

Toshihiko Okada, Shinji Fukuda, Koji Hase, Shin Nishiumi, Yoshihiro Izumi, Masaru Yoshida, Teruki Hagiwara, Rei Kawashima, Motomi Yamazaki, Tomoyuki Oshio, Takeshi Otsubo, Kyoko Inagaki-Ohara, Kazuki Kakimoto, Kazuhide Higuchi, Yuki I. Kawamura, Hiroshi Ohno, Taeko Dohi

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.

Original languageEnglish
Article number1654
JournalNature communications
Volume4
DOIs
Publication statusPublished - May 20 2013

Fingerprint

lactates
Microbiota
carcinogens
Starvation
Carcinogens
mice
Lactic Acid
Colon
Epithelial Cells
Aberrant Crypt Foci
Carcinogenesis
food intake
incidence
Cell proliferation
Bromodeoxyuridine
intestines
Enterocytes
Large Intestine
Incidence
Dietary Fiber

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Microbiota-derived lactate accelerates colon epithelial cell turnover in starvation-refed mice. / Okada, Toshihiko; Fukuda, Shinji; Hase, Koji; Nishiumi, Shin; Izumi, Yoshihiro; Yoshida, Masaru; Hagiwara, Teruki; Kawashima, Rei; Yamazaki, Motomi; Oshio, Tomoyuki; Otsubo, Takeshi; Inagaki-Ohara, Kyoko; Kakimoto, Kazuki; Higuchi, Kazuhide; Kawamura, Yuki I.; Ohno, Hiroshi; Dohi, Taeko.

In: Nature communications, Vol. 4, 1654, 20.05.2013.

Research output: Contribution to journalArticle

Okada, T, Fukuda, S, Hase, K, Nishiumi, S, Izumi, Y, Yoshida, M, Hagiwara, T, Kawashima, R, Yamazaki, M, Oshio, T, Otsubo, T, Inagaki-Ohara, K, Kakimoto, K, Higuchi, K, Kawamura, YI, Ohno, H & Dohi, T 2013, 'Microbiota-derived lactate accelerates colon epithelial cell turnover in starvation-refed mice', Nature communications, vol. 4, 1654. https://doi.org/10.1038/ncomms2668
Okada, Toshihiko ; Fukuda, Shinji ; Hase, Koji ; Nishiumi, Shin ; Izumi, Yoshihiro ; Yoshida, Masaru ; Hagiwara, Teruki ; Kawashima, Rei ; Yamazaki, Motomi ; Oshio, Tomoyuki ; Otsubo, Takeshi ; Inagaki-Ohara, Kyoko ; Kakimoto, Kazuki ; Higuchi, Kazuhide ; Kawamura, Yuki I. ; Ohno, Hiroshi ; Dohi, Taeko. / Microbiota-derived lactate accelerates colon epithelial cell turnover in starvation-refed mice. In: Nature communications. 2013 ; Vol. 4.
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