Butyrate-induced transcriptional changes in human colonic mucosa.
BACKGROUND
Fermentation of dietary fiber in the colon results in the production of short chain fatty acids (mainly propionate, butyrate and acetate). Butyrate modulates a wide range of processes, but its mechanism of action is mostly unknown. This study aimed to determine the effects of butyrate on the transcriptional regulation of human colonic mucosa in vivo.


RESULTS
Five hundred genes were found to be differentially expressed after a two week daily butyrate administration with enemas. Pathway analysis showed that the butyrate intervention mainly resulted in an increased transcriptional regulation of the pathways representing fatty acid oxidation, electron transport chain and oxidative stress. In addition, several genes associated with epithelial integrity and apoptosis, were found to be differentially expressed after the butyrate intervention.


CONCLUSIONS
Colonic administration of butyrate in concentrations that can be achieved by consumption of a high-fiber diet enhances the maintenance of colonic homeostasis in healthy subjects, by regulating fatty acid metabolism, electron transport and oxidative stress pathways on the transcriptional level and provide for the first time, detailed molecular insight in the transcriptional response of gut mucosa to butyrate.
Vanhoutvin
Steven A L W
SA
TI Food and Nutrition, Wageningen, The Netherlands. s.vanhoutvin@intmed.unimaas.nl
Troost
Freddy J
FJ
Hamer
Henrike M
HM
Lindsey
Patrick J
PJ
Koek
Ger H
GH
Jonkers
Daisy M A E
DM
Kodde
Andrea
A
Venema
Koen
K
Brummer
Robert J M
RJ
D001483:Base Sequence; D020148:Butyric Acid / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D017931:DNA Primers; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects*
D017931:DNA Primers; D020148:Butyric Acid
Carcinogenesis. 2007 Feb;28(2):240-5
17166881
Physiol Rev. 2001 Jul;81(3):1031-64
11427691
Nat Genet. 2002 May;31(1):19-20
11984561
Ageing Res Rev. 2005 May;4(2):288-314
15936251
Eur J Biochem. 2004 Jan;271(1):87-95
14686922
Adv Med Sci. 2007;52:83-8
18217395
Inflamm Bowel Dis. 2003 Mar;9(2):116-21
12769445
Mol Cell Biochem. 2000 Feb;205(1-2):149-61
10821433
Mayo Clin Proc. 1992 Mar;67(3):245-8
1545592
Int J Colorectal Dis. 1999 Aug;14(3):150-4
10460905
FEBS Lett. 2000 Jun 23;475(3):163-6
10869548
Mol Cell Biochem. 2003 Dec;254(1-2):21-36
14674679
JPEN J Parenter Enteral Nutr. 1992 Jan-Feb;16(1):43-8
1738218
Cell Growth Differ. 1996 May;7(5):647-53
8732674
Mol Genet Metab. 2006 Dec;89(4):332-8
16919490
Biochem J. 1997 Feb 1;321 ( Pt 3):713-9
9032458
Proc Nutr Soc. 2003 Feb;62(1):95-9
12740048
Oncogene. 2004 Aug 19;23(37):6304-15
15318170
Neurogastroenterol Motil. 2009 Sep;21(9):952-e76
19460106
Gastroenterology. 1995 Dec;109(6):1890-9
7498654
BMC Genomics. 2006 Sep 14;7:234
16972989
Arch Biochem Biophys. 1995 Mar 10;317(2):385-90
7893153
Scand J Gastroenterol. 1982 Oct;17(7):933-8
6130596
Genome Biol. 2003;4(1):R7
12540299
Eur J Clin Nutr. 2006 May;60(5):567-72
16340949
Life Sci. 1980 Oct 13;27(15):1351-8
7003281
Nucleic Acids Res. 2005 Nov 10;33(20):e175
16284200
J Nutr. 2007 Apr;137(4):916-22
17374654
Physiol Rev. 1990 Apr;70(2):567-90
2181501
Mol Cancer Res. 2006 Sep;4(9):645-53
16940161
Proc Nutr Soc. 1996 Nov;55(3):937-43
9004335
Arterioscler Thromb Vasc Biol. 1995 Dec;15(12):2273-83
7489253
Hum Mutat. 2001 Sep;18(3):169-89
11524729
Dig Dis Sci. 1992 Dec;37(12):1890-7
1473437
Gastroenterology. 2007 Dec;133(6):1916-27
18054563
Nat Genet. 2000 May;25(1):25-9
10802651
Carcinogenesis. 2003 Oct;24(10):1637-44
12896903
Carcinogenesis. 2005 Jun;26(6):1064-76
15746163
Mol Cancer Res. 2004 Dec;2(12):692-701
15634758
Gut. 2006 Dec;55(12):1692-3
17124152
J Gastroenterol Hepatol. 1999 Sep;14(9):873-9
10535468
FEBS Lett. 2006 May 29;580(13):3035-41
16678170
Proc Nutr Soc. 2003 Feb;62(1):107-15
12740065
Cancer Res. 2000 Aug 15;60(16):4561-72
10969808
Physiol Res. 2009;58(1):111-119
18198997
Physiol Rev. 2002 Apr;82(2):373-428
11917093
Dis Colon Rectum. 2005 Mar;48(3):549-59
15711862
Pediatr Res. 2007 Jan;61(1):37-41
17211138
Nat Biotechnol. 2006 Sep;24(9):1115-22
16964225
Funct Integr Genomics. 2007 Jul;7(3):193-205
17186197
J Cancer Res Clin Oncol. 2006 Aug;132(8):487-97
16788843
JPEN J Parenter Enteral Nutr. 2008 Jan-Feb;32(1):51-6
18165447
Aliment Pharmacol Ther. 2008 Jan 15;27(2):104-19
17973645
Gastroenterology. 2005 Mar;128(3):676-86
15765403
Nucleic Acids Res. 2009 Jan;37(Database issue):D868-72
19015125
Dig Dis Sci. 1989 Nov;34(11):1792-7
2582990
Aliment Pharmacol Ther. 2002 Dec;16(12):1997-2015
12452933
DNA Cell Biol. 2006 Jan;25(1):49-62
16405400
Biochem J. 1996 Dec 1;320 ( Pt 2):345-57
8973539
Biochem Soc Trans. 2005 Aug;33(Pt 4):733-5
16042588
J Pathol. 2003 Sep;201(1):28-36
12950014
Clin Nutr. 2009 Feb;28(1):88-93
19108937
Biochem Med. 1979 Dec;22(3):365-74
93966
J Biol Chem. 2007 Mar 30;282(13):9797-9804
17251186
Nutrition. 2005 Jun;21(6):740-8
15925300