5-Aminosalicylic acid alters the gut microbiota and altered microbiota transmitted vertically to offspring have protective effects against colitis.
Humans
Animals
Mice
Mesalamine
/ adverse effects
Gastrointestinal Microbiome
Colitis
/ chemically induced
Colitis, Ulcerative
/ chemically induced
Inflammation
/ drug therapy
Inflammatory Bowel Diseases
/ drug therapy
Anti-Inflammatory Agents
/ pharmacology
Dextran Sulfate
/ adverse effects
Disease Models, Animal
Colon
Mice, Inbred C57BL
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
28 07 2023
28 07 2023
Historique:
received:
20
03
2023
accepted:
26
07
2023
medline:
31
7
2023
pubmed:
29
7
2023
entrez:
28
7
2023
Statut:
epublish
Résumé
Although many therapeutic options are available for inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA) is still the key medication, particularly for ulcerative colitis (UC). However, the mechanism of action of 5-ASA remains unclear. The intestinal microbiota plays an important role in the pathophysiology of IBD, and we hypothesized that 5-ASA alters the intestinal microbiota, which promotes the anti-inflammatory effect of 5-ASA. Because intestinal inflammation affects the gut microbiota and 5-ASA can change the severity of inflammation, assessing the impact of inflammation and 5-ASA on the gut microbiota is not feasible in a clinical study of patients with UC. Therefore, we undertook a translational study to demonstrate a causal link between 5-ASA administration and alterations of the intestinal microbiota. Furthermore, by rigorously controlling environmental confounders and excluding the effect of 5-ASA itself with a vertical transmission model, we observed that the gut microbiota altered by 5-ASA affected host mucosal immunity and decreased susceptibility to dextran sulfate sodium-induce colitis. Although the potential intergenerational transmission of epigenetic changes needs to be considered in this study, these findings suggested that alterations in the intestinal microbiota induced by 5-ASA directed the host immune system towards an anti-inflammatory state, which underlies the mechanism of 5-ASA efficacy.
Identifiants
pubmed: 37507482
doi: 10.1038/s41598-023-39491-x
pii: 10.1038/s41598-023-39491-x
pmc: PMC10382598
doi:
Substances chimiques
Mesalamine
4Q81I59GXC
Anti-Inflammatory Agents
0
Dextran Sulfate
9042-14-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12241Informations de copyright
© 2023. The Author(s).
Références
Inflamm Bowel Dis. 2001 Aug;7(3):221-5
pubmed: 11515848
Int J Mol Med. 1999 Oct;4(4):437-43
pubmed: 10493988
PLoS One. 2012;7(8):e42529
pubmed: 22880019
J Exp Med. 2005 Jan 17;201(2):233-40
pubmed: 15657292
J Clin Invest. 2020 Oct 1;130(10):5197-5208
pubmed: 32516134
Immunity. 1996 May;4(5):471-81
pubmed: 8630732
Mucosal Immunol. 2014 Nov;7(6):1340-53
pubmed: 24670427
Nat Med. 2023 Mar;29(3):700-709
pubmed: 36823301
Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13780-5
pubmed: 17699621
J Biol Chem. 1999 Dec 17;274(51):36631-6
pubmed: 10593965
Biol Pharm Bull. 2019 Jan 1;42(1):81-86
pubmed: 30369547
Gastroenterology. 2005 Sep;129(3):969-84
pubmed: 16143135
Nat Rev Immunol. 2016 May 27;16(6):341-52
pubmed: 27231050
Aliment Pharmacol Ther. 1999 Mar;13(3):363-72
pubmed: 10102970
Nat Med. 2008 Mar;14(3):282-9
pubmed: 18264109
Dig Dis Sci. 2013 Jun;58(6):1546-59
pubmed: 23306855
Science. 2008 Jun 20;320(5883):1647-51
pubmed: 18497261
Environ Sci Pollut Res Int. 2021 Jun;28(23):28926-28964
pubmed: 33860421
Nat Methods. 2016 Jul;13(7):581-3
pubmed: 27214047
PeerJ. 2018 Jul 12;6:e5166
pubmed: 30013837
J Exp Med. 2009 Jul 6;206(7):1465-72
pubmed: 19564350
Inflamm Bowel Dis. 2009 Mar;15(3):341-52
pubmed: 18942757
Anticancer Res. 2012 Apr;32(4):1193-202
pubmed: 22493349
Clin J Gastroenterol. 2018 Feb;11(1):1-10
pubmed: 29285689
J Exp Med. 2005 Apr 18;201(8):1205-15
pubmed: 15824083
Am J Gastroenterol. 2009 Feb;104(2):437-43
pubmed: 19174792
Gastroenterology. 1989 Jul;97(1):38-41
pubmed: 2566551
J Exp Med. 2003 Dec 15;198(12):1951-7
pubmed: 14662908
PLoS One. 2016 Sep 06;11(9):e0162076
pubmed: 27598247
FASEB J. 2008 Mar;22(3):659-61
pubmed: 17942826
J Exp Med. 1991 Oct 1;174(4):915-24
pubmed: 1655948
N Engl J Med. 2009 Nov 19;361(21):2033-45
pubmed: 19890111
Biochim Biophys Acta. 2001 Sep 28;1533(2):110-8
pubmed: 11566448
Gut. 2006 Feb;55(2):205-11
pubmed: 16188921
Pflugers Arch. 2017 Jan;469(1):15-26
pubmed: 27904960
Br J Nutr. 2007 Apr;97(4):714-24
pubmed: 17349084
J Clin Invest. 2020 Oct 1;130(10):5100-5101
pubmed: 32831294
J Chromatogr A. 2006 Jun 30;1119(1-2):299-308
pubmed: 16466733
Cell Host Microbe. 2007 Aug 16;2(2):73-4
pubmed: 18005720
Ann N Y Acad Sci. 2017 Jun;1397(1):66-79
pubmed: 28493289
Inflamm Bowel Dis. 2014 Jan;20(1):21-35
pubmed: 24280877
J Biol Chem. 1999 Sep 10;274(37):26448-53
pubmed: 10473604
Cell. 1993 Oct 22;75(2):263-74
pubmed: 8402911
J Immunol. 1991 Dec 1;147(11):3815-22
pubmed: 1940369
Gut. 2014 Aug;63(8):1275-83
pubmed: 24021287
Behav Genet. 2002 Nov;32(6):435-43
pubmed: 12467341
Int J Clin Exp Pathol. 2014 Jul 15;7(8):4557-76
pubmed: 25197329
Front Immunol. 2019 Mar 11;10:277
pubmed: 30915065
Cell Rep. 2017 Jul 11;20(2):491-504
pubmed: 28700948
Am J Gastroenterol. 2000 Dec;95(12):3452-7
pubmed: 11151876
Front Microbiol. 2018 Jun 13;9:1274
pubmed: 29951050
Am J Physiol Gastrointest Liver Physiol. 2001 Oct;281(4):G1044-50
pubmed: 11557525
Cell Mol Gastroenterol Hepatol. 2017 Apr 11;4(1):135-151
pubmed: 28593185
Life Sci. 2021 Aug 1;278:119622
pubmed: 34015282
Int J Environ Res Public Health. 2018 Aug 07;15(8):
pubmed: 30087270
J Immunol. 1991 May 15;146(10):3444-51
pubmed: 1827484
Nat Biotechnol. 2019 Aug;37(8):852-857
pubmed: 31341288
Gut. 2004 May;53(5):685-93
pubmed: 15082587
Inflammation. 2015 Oct;38(5):1996-2006
pubmed: 25962374
Cell. 2006 Sep 22;126(6):1121-33
pubmed: 16990136