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

被引：120

作者：

Okada, Toshihiko ^{[1
,2
]}

Fukuda, Shinji ^{[3
,4
]}

Hase, Koji ^{[4
,5
]}

Nishiumi, Shin ^{[6
]}

Izumi, Yoshihiro ^{[6
]}

Yoshida, Masaru ^{[6
,7
]}

Hagiwara, Teruki ^{[1
]}

Kawashima, Rei ^{[1
]}

Yamazaki, Motomi ^{[1
]}

Oshio, Tomoyuki ^{[1
]}

Otsubo, Takeshi ^{[1
]}

Inagaki-Ohara, Kyoko ^{[1
]}

Kakimoto, Kazuki ^{[1
,2
]}

Higuchi, Kazuhide ^{[2
]}

Kawamura, Yuki I. ^{[1
]}

Ohno, Hiroshi ^{[3
,4
]}

Dohi, Taeko ^{[1
,8
]}

机构：

[1] Natl Ctr Global Hlth & Med, Res Inst, Res Ctr Hepatitis & Immunol, Dept Gastroenterol, Ichikawa, Chiba 2728516, Japan

[2] Osaka Med Coll, Dept Internal Med 2, Takatsuki, Osaka 5698686, Japan

[3] RIKEN, Res Ctr Allergy & Immunol, Lab Epithelial Immunobiol, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[4] Yokohama City Univ, Grad Sch Nanobiosci, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[5] Bioenvironm Epigenet, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[6] Kobe Univ, Grad Sch Med, Div Gastroenterol,Dept Internal Med, Chuo Ku, Kobe, Hyogo 6500017, Japan

[7] Kobe Univ, Grad Sch Med, Div Metabol Res,Dept Internal Med, Chuo Ku, Kobe, Hyogo 6500017, Japan

[8] RIKEN, Res Ctr Allergy & Immunol, Open Lab Allergy Res, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

基金：

日本科学技术振兴机构;

关键词：

DISTAL ULCERATIVE-COLITIS; CALORIE RESTRICTION; METABOLIC DYNAMICS; BUTYRATE ENEMAS; INTESTINE; RESPONSES; PROLIFERATION; NUTRITION; DISEASE; MUCOSA;

D O I：

10.1038/ncomms2668

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

共 39 条

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