Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation.
Adenomatous Polyposis Coli
/ microbiology
Animals
Bile Acids and Salts
/ metabolism
Colitis
/ etiology
Colonic Pouches
/ microbiology
Disease Models, Animal
Dysbiosis
/ complications
Feces
/ microbiology
Humans
Inflammation
/ drug therapy
Intestines
/ drug effects
Metagenome
Mice
Microbiota
Receptors, G-Protein-Coupled
/ drug effects
Ruminococcus
/ isolation & purification
Transcriptome
bile acids
colitis
dysbiosis
inflammatory bowel disease
metabolomics
pouchitis
ulcerative colitis
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
08 04 2020
08 04 2020
Historique:
received:
09
12
2018
revised:
22
12
2019
accepted:
24
01
2020
pubmed:
27
2
2020
medline:
30
12
2020
entrez:
27
2
2020
Statut:
ppublish
Résumé
Secondary bile acids (SBAs) are derived from primary bile acids (PBAs) in a process reliant on biosynthetic capabilities possessed by few microbes. To evaluate the role of BAs in intestinal inflammation, we performed metabolomic, microbiome, metagenomic, and transcriptomic profiling of stool from ileal pouches (surgically created resevoirs) in colectomy-treated patients with ulcerative colitis (UC) versus controls (familial adenomatous polyposis [FAP]). We show that relative to FAP, UC pouches have reduced levels of lithocholic acid and deoxycholic acid (normally the most abundant gut SBAs), genes required to convert PBAs to SBAs, and Ruminococcaceae (one of few taxa known to include SBA-producing bacteria). In three murine colitis models, SBA supplementation reduces intestinal inflammation. This anti-inflammatory effect is in part dependent on the TGR5 bile acid receptor. These data suggest that dysbiosis induces SBA deficiency in inflammatory-prone UC patients, which promotes a pro-inflammatory state within the intestine that may be treated by SBA restoration.
Identifiants
pubmed: 32101703
pii: S1931-3128(20)30062-7
doi: 10.1016/j.chom.2020.01.021
pmc: PMC8172352
mid: NIHMS1568778
pii:
doi:
Substances chimiques
Bile Acids and Salts
0
Gpbar1 protein, mouse
0
Receptors, G-Protein-Coupled
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
659-670.e5Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK101119
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK085025
Pays : United States
Organisme : NIDDK NIH HHS
ID : L30 DK106876
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001085
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR001083
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR003143
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR003142
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests All authors declare no competing interests.
Références
Therap Adv Gastroenterol. 2010 Nov;3(6):335-48
pubmed: 21180613
J Hepatol. 2013 May;58(5):949-55
pubmed: 23333527
Cochrane Database Syst Rev. 2015 Nov 23;(11):CD001176
pubmed: 26593456
Inflamm Bowel Dis. 2011 May;17(5):1092-100
pubmed: 20845425
Gastroenterology. 2018 May;154(6):1751-1763.e2
pubmed: 29408609
Gut. 2013 Apr;62(4):531-9
pubmed: 22993202
Expert Rev Gastroenterol Hepatol. 2009 Oct;3(5):547-59
pubmed: 19817675
PLoS One. 2012;7(9):e44328
pubmed: 22957064
Gastroenterology. 2010 Nov;139(5):1549-58, 1558.e1
pubmed: 20691689
Cell Rep. 2019 Mar 5;26(10):2704-2719.e6
pubmed: 30840892
Nat Rev Gastroenterol Hepatol. 2014 Jan;11(1):55-67
pubmed: 23982684
World J Hepatol. 2015 Dec 8;7(28):2811-8
pubmed: 26668692
J Pathol. 2003 Jan;199(1):28-35
pubmed: 12474223
Nat Rev Immunol. 2016 May 27;16(6):341-52
pubmed: 27231050
Front Immunol. 2018 Aug 13;9:1853
pubmed: 30150987
Nat Immunol. 2015 Feb;16(2):207-213
pubmed: 25531831
Medicine (Baltimore). 2014 Aug;93(8):e51
pubmed: 25121355
Semin Immunopathol. 2015 Jan;37(1):47-55
pubmed: 25420450
Microbiome. 2019 Aug 31;7(1):126
pubmed: 31472697
Dig Dis Sci. 2003 Aug;48(8):1431-44
pubmed: 12924634
PLoS One. 2018 May 8;13(5):e0196977
pubmed: 29738579
Cell Host Microbe. 2016 Nov 9;20(5):561-571
pubmed: 27832587
J Lipid Res. 2006 Feb;47(2):241-59
pubmed: 16299351
Front Cell Infect Microbiol. 2016 Dec 20;6:191
pubmed: 28066726
Gastroenterol Hepatol (N Y). 2008 May;4(5):355-61
pubmed: 21904509
Nat Protoc. 2007;2(3):541-6
pubmed: 17406617
Am J Clin Nutr. 1978 Oct;31(10 Suppl):S243-S247
pubmed: 707382
Inflamm Bowel Dis. 2006 Feb;12(2):106-11
pubmed: 16432374
Nature. 2019 May;569(7758):655-662
pubmed: 31142855
ILAR J. 2015;56(2):205-17
pubmed: 26323630
PLoS One. 2014 Jul 30;9(7):e103337
pubmed: 25076055
Dig Dis. 2012;30(4):351-7
pubmed: 22796796
Int J Syst Evol Microbiol. 2001 Jan;51(Pt 1):39-44
pubmed: 11211270
PLoS One. 2017 May 11;12(5):e0176715
pubmed: 28493883
Dig Dis Sci. 2018 Jul;63(7):1890-1899
pubmed: 29777439
J Am Coll Surg. 2003 Dec;197(6):974-84
pubmed: 14644286
Genome Biol. 2010;11(10):R106
pubmed: 20979621
Neurogastroenterol Motil. 2012 Jun;24(6):513-20, e246-7
pubmed: 22356587
mSphere. 2016 Jan 06;1(1):
pubmed: 27239562
Dig Dis. 2017;35(3):169-177
pubmed: 28249284
Colorectal Dis. 2005 Nov;7(6):563-70
pubmed: 16232236
Pharmacol Res. 2016 Feb;104:9-21
pubmed: 26706784
PLoS One. 2013 Sep 24;8(9):e66934
pubmed: 24086242
Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6252-7
pubmed: 21436049
Immunology. 2013 May;139(1):19-29
pubmed: 23566200
Ann Surg. 1997 Oct;226(4):514-9; discussion 519-21
pubmed: 9351719
Sci Rep. 2016 Jun 28;6:28786
pubmed: 27349927
Gut Microbes. 2013 Sep-Oct;4(5):382-7
pubmed: 23851335
Nutr Res. 2017 Oct;46:11-21
pubmed: 29173647
Dig Liver Dis. 2014 Apr;46(4):302-12
pubmed: 24411485
Nucleic Acids Res. 2001 May 1;29(9):e45
pubmed: 11328886
J Lipid Res. 1979 Mar;20(3):325-33
pubmed: 36438
Gut Microbes. 2015;6(1):48-56
pubmed: 25559083
Dig Endosc. 2017 Jan;29(1):26-34
pubmed: 27681447
Cell Metab. 2017 Jul 5;26(1):110-130
pubmed: 28625867
Gastroenterology. 2017 Feb;152(2):327-339.e4
pubmed: 27769810
Int Immunopharmacol. 2013 Feb;15(2):372-80
pubmed: 23246254
Gut. 2011 Apr;60(4):463-72
pubmed: 21242261
Cell Host Microbe. 2019 May 8;25(5):695-705.e5
pubmed: 31031170
Appl Environ Microbiol. 2005 Dec;71(12):8228-35
pubmed: 16332807
Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13780-5
pubmed: 17699621
Sci Rep. 2016 Sep 13;6:32889
pubmed: 27620138
Nature. 2015 Jan 8;517(7533):205-8
pubmed: 25337874
Gastroenterology. 2003 May;124(5):1202-9
pubmed: 12730861
Mol Aspects Med. 2017 Aug;56:54-65
pubmed: 28602676
Gut. 2019 Oct;68(10):1791-1800
pubmed: 30816855
Inflamm Bowel Dis. 2009 Dec;15(12):1803-11
pubmed: 19637361
J Inflamm Res. 2017 Jun 10;10:63-73
pubmed: 28652796
Nat Chem Biol. 2015 Sep;11(9):685-90
pubmed: 26192599
Lancet. 2018 Dec 23;390(10114):2769-2778
pubmed: 29050646
Neurogastroenterol Motil. 2010 Jul;22(7):814-25, e227-8
pubmed: 20236244
Cell Metab. 2011 Dec 7;14(6):747-57
pubmed: 22152303
Cell Host Microbe. 2014 Mar 12;15(3):382-392
pubmed: 24629344
Toxicol Appl Pharmacol. 2018 Sep 15;355:198-210
pubmed: 30008377
Biochim Biophys Acta. 2008 Jan-Feb;1781(1-2):16-25
pubmed: 18047844
Am J Physiol Gastrointest Liver Physiol. 2007 Jul;293(1):G256-63
pubmed: 17412828
Mayo Clin Proc. 2019 Jan;94(1):155-165
pubmed: 30611442