title: Mosapride citrate improves nonalcoholic steatohepatitis with increased fecal lactic acid bacteria and plasma glucagon-like peptide-1 level in a rodent model.
abstract: Several lines of evidence have suggested a role of gut microbiota in the etiology of nonalcoholic steatohepatitis (NASH). NASH subjects reportedly showed a prolonged orocecal transit time coexistent with small intestinal bacterial overgrowth. We considered the possibility that enhanced gastrointestinal motility would influence gut microbiota and thus investigated the effects of the gastroprokinetic agent mosapride citrate (MC) on gut microbiota and the development of NASH using a methionine-choline deficient (MCD) diet-fed rodent model. Mice were divided into three groups, given the normal chow diet (NCD), the MCD diet, or the MCD diet containing 10 mg·kg(-1)·day(-1) of MC (MCD plus MC) for 6 wk. NASH development was evaluated based on hepatic histochemical findings, serum parameters and various mRNA and/or protein expression levels. MC treatment suppressed MCD diet-induced NASH development, with reduced serum lipopolysaccharide and increased plasma glucagon-like peptide-1 (GLP-1) concentrations. Calculation of the relative abundance of each strain based on gut microbiota analyses indicated lactic acid bacteria specifically, such as Bifidobacterium and Lactobacillus, in feces to be decreased in the MCD, compared with the NCD group. Interestingly, the reduction in lactic acid bacteria in the MCD diet group was reversed in the MCD plus MC group. In addition, colon inflammation observed in the MCD diet group was reduced in the MCD plus MC group. Therefore, MC showed a protective effect against MCD diet-induced NASH development in our rodent model, with possible involvements of increased fecal lactic acid bacteria, protection against colon inflammation and elevated plasma GLP-1.
authors.affiliation: Department of Medical Science, Graduate School of Medicine, University of Hiroshima, Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan;
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Okubo
authors.affiliation: Department of Medical Science, Graduate School of Medicine, University of Hiroshima, Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan;
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakatsu
authors.affiliation: Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan;
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakoda
authors.affiliation: Institute for Adult Disease, Asahi Life Foundation, Bakuro-cho, Chuo-ku, Tokyo, Japan;
authors.forename: Akifumi
authors.initials: A
authors.lastname: Kushiyama
authors.affiliation: Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan;
authors.forename: Midori
authors.initials: M
authors.lastname: Fujishiro
authors.affiliation: Department of Medical Science, Graduate School of Medicine, University of Hiroshima, Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan;
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Fukushima
authors.affiliation: Department of Medical Science, Graduate School of Medicine, University of Hiroshima, Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan;
authors.forename: Yasuka
authors.initials: Y
authors.lastname: Matsunaga
authors.affiliation: Department of Molecular and Internal Medicine, Institute of Biomedical and Health Sciences, University of Hiroshima, Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan; and.
authors.forename: Haruya
authors.initials: H
authors.lastname: Ohno
authors.affiliation: Department of Molecular and Internal Medicine, Institute of Biomedical and Health Sciences, University of Hiroshima, Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan; and.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Yoneda
authors.affiliation: Department of Medical Science, Graduate School of Medicine, University of Hiroshima, Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan;
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kamata
authors.affiliation: Department of Dental Science for Health Promotion, Division of Cervico-Gnathostomatology, Graduate School of Biomedical Sciences, University of Hiroshima, Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Shinjo
authors.affiliation: Department of Dental Science for Health Promotion, Division of Cervico-Gnathostomatology, Graduate School of Biomedical Sciences, University of Hiroshima, Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan.
authors.forename: Misaki
authors.initials: M
authors.lastname: Iwashita
authors.affiliation: Department of Dental Science for Health Promotion, Division of Cervico-Gnathostomatology, Graduate School of Biomedical Sciences, University of Hiroshima, Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan.
authors.forename: Fusanori
authors.initials: F
authors.lastname: Nishimura
authors.affiliation: Department of Medical Science, Graduate School of Medicine, University of Hiroshima, Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan; tasano@hiroshima-u.ac.jp.
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002796:Choline Deficiency / Q000378:metabolism; D005243:Feces / Q000737:chemistry / Q000382:microbiology*; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D007249:Inflammation / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology*; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D001549:Benzamides; D009025:Morpholines; D019344:Lactic Acid; D052216:Glucagon-Like Peptide 1; C062720:mosapride
keywords: glucagon-like peptide-1; gut microbiota; inflammation; mosapride citrate; nonalcoholic steatohepatitis