Bacterial and Fungal Profiles as Markers of Infliximab Drug Response in Inflammatory Bowel Disease.


Journal

Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676

Informations de publication

Date de publication:
22 Jun 2021
Historique:
pubmed: 11 12 2020
medline: 15 12 2021
entrez: 10 12 2020
Statut: ppublish

Résumé

Inflammatory bowel diseases [IBDs], Crohn's disease [CD] and ulcerative colitis [UC], are globally increasing chronic gastro-intestinal inflammatory disorders associated with altered gut microbiota. Infliximab [IFX], a tumour necrosis factor [TNF]-alpha blocker, is used to treat IBD patients successfully, though one-third of the patients do not respond to therapy. No reliable biomarkers are available for prediction of IFX response. Our aims were to investigate the faecal bacterial and fungal communities during IFX therapy and find predictors for IFX treatment response in IBD patients. A total of 72 IBD patients [25 CD and 47 UC] started IFX therapy and were followed for 1 year or until IFX treatment was discontinued. An amplicon sequencing approach, targeting the bacterial 16S rRNA gene and fungal ITS 1 region separately, was used to determine the microbiota profiles in faecal samples collected before IFX therapy and 2, 6, and 12 weeks and 1 year after initiation of therapy. The response to IFX was evaluated by colonoscopy and clinically at 12 weeks after initiation. Both faecal bacterial and fungal profiles differed significantly between response groups before start of IFX treatment. Non-responders had lower abundances of short chain fatty acid producers, particularly of the class Clostridia, and higher abundances of pro-inflammatory bacteria and fungi, such as the genus Candida, compared with responders. This was further indicated by bacterial taxa predicting the response in both CD and UC patients [area under the curve >0.8]. Faecal bacterial and fungal microbiota composition could provide a predictive tool to estimate IFX response in IBD patients.

Sections du résumé

BACKGROUND AND AIMS OBJECTIVE
Inflammatory bowel diseases [IBDs], Crohn's disease [CD] and ulcerative colitis [UC], are globally increasing chronic gastro-intestinal inflammatory disorders associated with altered gut microbiota. Infliximab [IFX], a tumour necrosis factor [TNF]-alpha blocker, is used to treat IBD patients successfully, though one-third of the patients do not respond to therapy. No reliable biomarkers are available for prediction of IFX response. Our aims were to investigate the faecal bacterial and fungal communities during IFX therapy and find predictors for IFX treatment response in IBD patients.
METHODS METHODS
A total of 72 IBD patients [25 CD and 47 UC] started IFX therapy and were followed for 1 year or until IFX treatment was discontinued. An amplicon sequencing approach, targeting the bacterial 16S rRNA gene and fungal ITS 1 region separately, was used to determine the microbiota profiles in faecal samples collected before IFX therapy and 2, 6, and 12 weeks and 1 year after initiation of therapy. The response to IFX was evaluated by colonoscopy and clinically at 12 weeks after initiation.
RESULTS RESULTS
Both faecal bacterial and fungal profiles differed significantly between response groups before start of IFX treatment. Non-responders had lower abundances of short chain fatty acid producers, particularly of the class Clostridia, and higher abundances of pro-inflammatory bacteria and fungi, such as the genus Candida, compared with responders. This was further indicated by bacterial taxa predicting the response in both CD and UC patients [area under the curve >0.8].
CONCLUSIONS CONCLUSIONS
Faecal bacterial and fungal microbiota composition could provide a predictive tool to estimate IFX response in IBD patients.

Identifiants

pubmed: 33300552
pii: 6029424
doi: 10.1093/ecco-jcc/jjaa252
doi:

Substances chimiques

Biomarkers, Pharmacological 0
Tumor Necrosis Factor Inhibitors 0
Infliximab B72HH48FLU

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1019-1031

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Auteurs

Rebecka Ventin-Holmberg (R)

Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.

Anja Eberl (A)

Department of Gastroenterology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Schahzad Saqib (S)

Human Microbiome Research Program, University of Helsinki, Helsinki, Finland.

Katri Korpela (K)

Human Microbiome Research Program, University of Helsinki, Helsinki, Finland.

Seppo Virtanen (S)

Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Taina Sipponen (T)

Department of Gastroenterology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Anne Salonen (A)

Human Microbiome Research Program, University of Helsinki, Helsinki, Finland.

Päivi Saavalainen (P)

Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.

Eija Nissilä (E)

Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.

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Classifications MeSH