Commensal bacteria promote azathioprine therapy failure in inflammatory bowel disease via decreasing 6-mercaptopurine bioavailability.

Animals Mice Mercaptopurine / therapeutic use Azathioprine / therapeutic use Immunosuppressive Agents / therapeutic use Biological Availability Inflammatory Bowel Diseases / drug therapy Colitis / chemically induced Bacteria
6-mercaptopurine azathioprine therapy failure biotransformation inflammatory bowel disease microbiome

Journal

Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894

Informations de publication

Date de publication:
15 08 2023
Historique:
received: 28 11 2022
revised: 07 06 2023
accepted: 18 07 2023
medline: 18 8 2023
pubmed: 17 8 2023
entrez: 16 8 2023
Statut: ppublish

Résumé

Azathioprine (AZA) therapy failure, though not the primary cause, contributes to disease relapse and progression in inflammatory bowel disease (IBD). However, the role of gut microbiota in AZA therapy failure remains poorly understood. We found a high prevalence of Blautia wexlerae in patients with IBD with AZA therapy failure, associated with shorter disease flare survival time. Colonization of B. wexlerae increased inflammatory macrophages and compromised AZA's therapeutic efficacy in mice with intestinal colitis. B. wexlerae colonization reduced 6-mercaptopurine (6-MP) bioavailability by enhancing selenium-dependent xanthine dehydrogenase (sd-XDH) activity. The enzyme sd-XDH converts 6-MP into its inactive metabolite, 6-thioxanthine (6-TX), thereby impairing its ability to inhibit inflammation in mice. Supplementation with Bacillus (B.) subtilis enriched in hypoxanthine phosphoribosyltransferase (HPRT) effectively mitigated B. wexlerae-induced AZA treatment failure in mice with intestinal colitis. These findings emphasize the need for tailored management strategies based on B. wexlerae levels in patients with IBD.

Identifiants

DOI: 10.1016/j.xcrm.2023.101153 PMID: 37586320 PMC: PMC10439275
pubmed: 37586320
pii: S2666-3791(23)00306-3
doi: 10.1016/j.xcrm.2023.101153
pmc: PMC10439275
pii:
doi:

Substances chimiques

Mercaptopurine E7WED276I5
Azathioprine MRK240IY2L
Immunosuppressive Agents 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

101153

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Références

J Crohns Colitis. 2017 Jan;11(1):3-25
pubmed: 27660341
Bioinformatics. 2018 Sep 1;34(17):i884-i890
pubmed: 30423086
Nat Biomed Eng. 2022 Jul;6(7):867-881
pubmed: 35798834
J Gastroenterol Hepatol. 2018 Jan;33(1):141-149
pubmed: 28475813
Benef Microbes. 2015;6(4):583-90
pubmed: 25691104
Gut. 2017 Jan;66(1):59-69
pubmed: 27411368
N Engl J Med. 2020 Dec 31;383(27):2652-2664
pubmed: 33382932
Int J Biol Macromol. 2022 Nov 1;220:22-32
pubmed: 35932810
Chem Biol Interact. 2010 Jul 30;186(2):110-7
pubmed: 20434437
Lab Invest. 1993 Aug;69(2):238-49
pubmed: 8350599
Nat Methods. 2017 Oct 31;14(11):1023-1024
pubmed: 29088129
Science. 2019 Feb 8;363(6427):
pubmed: 30733391
Nat Commun. 2022 Aug 18;13(1):4477
pubmed: 35982037
J Dig Dis. 2021 Jun;22(6):298-317
pubmed: 33905603
Genome Med. 2017 Nov 28;9(1):103
pubmed: 29183332
Cell Host Microbe. 2018 May 9;23(5):653-660.e5
pubmed: 29746836
Aliment Pharmacol Ther. 2006 Sep 1;24(5):715-29
pubmed: 16918876
J Bacteriol. 1997 Apr;179(8):2540-50
pubmed: 9098051
mSystems. 2020 Mar 24;5(2):
pubmed: 32209719
Nat Commun. 2019 Mar 4;10(1):1014
pubmed: 30833550
Genes (Basel). 2019 Apr 04;10(4):
pubmed: 30987408
Gut. 2020 Aug;69(8):1510-1519
pubmed: 32409589
Science. 2021 Oct 08;374(6564):216-224
pubmed: 34618582
Gut. 2021 Dec;70(12):2261-2272
pubmed: 33441378
Nat Rev Gastroenterol Hepatol. 2012 Oct;9(10):599-608
pubmed: 22907164
Lancet Gastroenterol Hepatol. 2020 Dec;5(12):1089-1100
pubmed: 33181088
Am J Gastroenterol. 2015 Sep;110(9):1324-38
pubmed: 26303131
Science. 2012 Jun 8;336(6086):1262-7
pubmed: 22674330
Ann Rheum Dis. 2019 Jun;78(6):736-745
pubmed: 30926722
Genome Biol. 2018 Feb 6;19(1):15
pubmed: 29409532
Sci Immunol. 2019 Apr 19;4(34):
pubmed: 31004013
Immunity. 2022 May 10;55(5):847-861.e10
pubmed: 35545033
Nat Protoc. 2007;2(3):541-6
pubmed: 17406617
Nature. 2007 Jul 26;448(7152):427-34
pubmed: 17653185
Science. 2019 Jun 14;364(6445):
pubmed: 31196984
Cell. 2020 Jun 25;181(7):1661-1679.e22
pubmed: 32526207
EClinicalMedicine. 2022 Mar 05;45:101332
pubmed: 35274092
Nat Commun. 2019 Jan 18;10(1):310
pubmed: 30659181
Pharmacotherapy. 2020 Feb;40(2):125-132
pubmed: 31885095
Cell. 2019 Nov 14;179(5):1160-1176.e24
pubmed: 31730855
Mucosal Immunol. 2010 Sep;3(5):450-60
pubmed: 20445502
Can J Microbiol. 2018 May;64(5):327-337
pubmed: 29401402
J Microbiol Biotechnol. 2022 Aug 28;32(8):1011-1016
pubmed: 35879295
Cell Metab. 2015 May 5;21(5):667-77
pubmed: 25955204
Nature. 2021 Sep;597(7877):533-538
pubmed: 34497420
PeerJ. 2016 Oct 18;4:e2584
pubmed: 27781170
Nat Commun. 2017 Oct 16;8(1):837
pubmed: 29038503
Nature. 2012 Sep 13;489(7415):242-9
pubmed: 22972297
N Engl J Med. 2005 Dec 8;353(23):2462-76
pubmed: 16339095
Gut. 2016 Mar;65(3):415-425
pubmed: 26045134
Nat Rev Gastroenterol Hepatol. 2017 Oct;14(10):573-584
pubmed: 28743984
Int J Clin Exp Pathol. 2014 Jul 15;7(8):4557-76
pubmed: 25197329
Gut. 2002 Apr;50(4):485-9
pubmed: 11889067
Science. 2015 Nov 27;350(6264):1079-84
pubmed: 26541610
Nat Med. 2023 Mar;29(3):700-709
pubmed: 36823301
Blood. 1975 Jul;46(1):51-64
pubmed: 1131426
Gut Microbes. 2020 Jul 3;11(4):944-961
pubmed: 32138587
Microb Pathog. 2019 Feb;127:304-315
pubmed: 30529513
Nat Rev Dis Primers. 2018 Apr 12;4:18017
pubmed: 29644994
Gastroenterology. 2020 Sep;159(3):969-983.e4
pubmed: 32387495
Nature. 2021 Dec;600(7887):110-115
pubmed: 34819672
Nature. 2019 Jun;570(7762):462-467
pubmed: 31158845
Nat Rev Microbiol. 2022 Jul;20(7):431-443
pubmed: 35102308

Auteurs

Yuqing Yan (Y)

State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.

Zhenhua Wang (Z)

State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.

Yi-Lu Zhou (YL)

State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.

Ziyun Gao (Z)

State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.

Lijun Ning (L)

State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.

Ying Zhao (Y)

State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.

Baoqin Xuan (B)

State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.

Yanru Ma (Y)

State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.

Tianying Tong (T)

State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.

Xiaowen Huang (X)

State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.

Muni Hu (M)

State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.

Jing-Yuan Fang (JY)

State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.

Zhe Cui (Z)

Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 145 Middle Shandong Road, Shanghai 200001, China. Electronic address: drcui1568@163.com.

Haoyan Chen (H)

State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China. Electronic address: haoyanchen@sjtu.edu.cn.

Jie Hong (J)

State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China. Electronic address: jiehong97@sjtu.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Commensal bacteria promote azathioprine...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Commensal bacteria promote azathioprine...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Purines › Mercaptopurine › Commensal bacteria promote azathioprine...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléosides › Thionucléosides › Azathioprine › Commensal bacteria promote azathioprine...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Facteurs immunologiques › Immunosuppresseurs › Commensal bacteria promote azathioprine...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Pharmacocinétique › Biodisponibilité › Commensal bacteria promote azathioprine...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies inflammatoires intestinales › Commensal bacteria promote azathioprine...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies du côlon › Colite › Commensal bacteria promote azathioprine...
questionsmedicales.fr › Bactéries › Commensal bacteria promote azathioprine...