title: Epithelial cell proliferation arrest induced by lactate and acetate from Lactobacillus casei and Bifidobacterium breve.
abstract: In an attempt to identify and characterize how symbiotic bacteria of the gut microbiota affect the molecular and cellular mechanisms of epithelial homeostasis, intestinal epithelial cells were co-cultured with either Lactobacillus or Bifidobacterium as bona fide symbionts to examine potential gene modulations. In addition to genes involved in the innate immune response, genes encoding check-point molecules controlling the cell cycle were among the most modulated in the course of these interactions. In the m-ICcl2 murine cell line, genes encoding cyclin E1 and cyclin D1 were strongly down regulated by L. casei and B. breve respectively. Cell proliferation arrest was accordingly confirmed. Short chain fatty acids (SCFA) were the effectors of this modulation, alone or in conjunction with the acidic pH they generated. These results demonstrate that the production of SCFAs, a characteristic of these symbiotic microorganisms, is potentially an essential regulatory effector of epithelial proliferation in the gut.
authors: Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France.
authors: Takahiro
authors: T
authors: Matsuki
authors: Thierry
authors: T
authors: Pédron
authors: Béatrice
authors: B
authors: Regnault
authors: Céline
authors: C
authors: Mulet
authors: Taeko
authors: T
authors: Hara
authors: Philippe J
authors: PJ
authors: Sansonetti
mesh_terms: D000085:Acetates / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001644:Bifidobacterium / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology; D019344:Lactic Acid / Q000378:metabolism* / Q000494:pharmacology; D007780:Lacticaseibacillus casei / Q000378:metabolism*; D051379:Mice; D064307:Microbiota; D013559:Symbiosis
chemical_list: D000085:Acetates; D019927:Cyclin E; D019938:Cyclin D1; D019344:Lactic Acid
references: Cell Microbiol. 2011 Jan;13(1):123-34
references: 20946259
references: Nature. 1970 Aug 15;227(5259):680-5
references: 5432063
references: Am J Clin Nutr. 1984 Feb;39(2):338-42
references: 6320630
references: Physiol Rev. 1990 Apr;70(2):567-90
references: 2181501
references: Science. 2001 Feb 2;291(5505):881-4
references: 11157169
references: Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16767-72
references: 18931303
references: J Nutr Biochem. 2008 Sep;19(9):587-93
references: 18061431
references: Nature. 2011 Jan 27;469(7331):543-7
references: 21270894
references: Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):31-6
references: 11134512
references: J Biosci Bioeng. 2010 Nov;110(5):547-52
references: 20580604
references: Cell Mol Immunol. 2011 Mar;8(2):110-20
references: 21278760
references: Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8796-800
references: 1924341
references: Cell Microbiol. 2011 May;13(5):653-9
references: 21338464
references: Mucosal Immunol. 2008 Nov;1 Suppl 1:S10-4
references: 19079220
references: Am J Physiol Cell Physiol. 2012 May 15;302(10):C1421-33
references: 22460710
references: ISME J. 2010 Sep;4(9):1094-8
references: 20664551
references: Cancer Res. 2003 Mar 1;63(5):951-7
references: 12615708
references: Curr Opin Microbiol. 2011 Feb;14(1):92-8
references: 21215681
references: Cancer Res. 2012 Feb 15;72(4):939-48
references: 22184616
references: J Gastroenterol Hepatol. 2006 Jan;21(1 Pt 2):209-18
references: 16460475
references: Am J Physiol. 1996 Jun;270(6 Pt 1):C1666-74
references: 8764149
references: Oncol Res. 2003;13(6-10):405-8
references: 12725531
references: Future Microbiol. 2009 Sep;4(7):867-77
references: 19722840
references: J Exp Med. 2003 Oct 20;198(8):1225-35
references: 14568981
references: Cell Microbiol. 2008 Apr;10(4):921-9
references: 18005237
references: Biostatistics. 2003 Apr;4(2):249-64
references: 12925520
references: Gastroenterology. 1989 Mar;96(3):736-49
references: 2914637
references: Am J Physiol Gastrointest Liver Physiol. 2005 Aug;289(2):G220-6
references: 15831710
references: Am J Physiol Gastrointest Liver Physiol. 2011 Sep;301(3):G401-24
references: 21700901
references: J Nutr. 1993 Sep;123(9):1522-30
references: 8395594
references: Nat Protoc. 2008;3(6):1101-8
references: 18546601
references: J Immunol. 2005 Jun 1;174(11):7278-84
references: 15905574
references: Appl Environ Microbiol. 1981 Dec;42(6):996-1001
references: 7198427
references: Cell Microbiol. 2006 Nov;8(11):1740-52
references: 16759223
references: Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3303-7
references: 7724557
references: Trends Microbiol. 2005 Mar;13(3):103-10
references: 15737728
references: J Immunol. 2006 Jan 15;176(2):1228-37
references: 16394013
references: Cell. 2007 Aug 24;130(4):611-23
references: 17719540
references: Nature. 2011 Jun 15;474(7351):327-36
references: 21677749
references: Immunity. 2003 Jun;18(6):739-49
references: 12818156
references: Cell Host Microbe. 2008 Jun 12;3(6):344-7
references: 18541210
references: Science. 2009 Dec 18;326(5960):1694-7
references: 19892944
references: Cell Cycle. 2008 May 1;7(9):1178-83
references: 18418037
references: Infect Immun. 2009 Nov;77(11):4696-703
references: 19720753
references: Physiol Rev. 2010 Jul;90(3):859-904
references: 20664075
references: Curr Opin Microbiol. 2005 Feb;8(1):83-91
references: 15694861
references: Int J Food Microbiol. 2010 Oct 15;143(3):87-102
references: 20801536
references: Science. 2006 Aug 11;313(5788):848-51
references: 16902142