Microbial Butyrate Synthesis Indicates Therapeutic Efficacy of Azathioprine in IBD Patients.
Adult
Antimetabolites
/ administration & dosage
Azathioprine
/ administration & dosage
Bacteroidetes
/ isolation & purification
Biosynthetic Pathways
/ drug effects
Butyrates
/ metabolism
Colitis, Ulcerative
/ drug therapy
Computer Simulation
Correlation of Data
Crohn Disease
/ drug therapy
Female
Gastrointestinal Microbiome
/ drug effects
Humans
Male
Middle Aged
Proteobacteria
/ isolation & purification
Remission Induction
Treatment Outcome
Tumor Necrosis Factor Inhibitors
/ administration & dosage
Azathioprine
IBD
microbiota
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:
13 Jan 2021
13 Jan 2021
Historique:
pubmed:
21
7
2020
medline:
14
10
2021
entrez:
21
7
2020
Statut:
ppublish
Résumé
The microbial ecosystem seems to be an important player for therapeutic intervenption in inflammatory bowel disease [IBD]. We assessed longitudinal microbiome changes in IBD patients undergoing therapy with either azathioprine [AZA] or anti-tumour necrosis factor [anti-TNF] antibodies. We predicted the metabolic microbial community exchange and linked it to clinical outcome. Faecal and blood samples were collected from 65 IBD patients at baseline and after 12 and 30 weeks on therapy. Clinical remission was defined as Crohn's Disease Activity Index [CDAI] < 150 in Crohn´s disease [CD], partial Mayo score <2 in ulcerative colitis [UC], and faecal calprotectin values <150 µg/g and C-reactive protein <5 mg/dl. 16S rRNA amplicon sequencing was performed. To predict microbial community metabolic processes, we constructed multispecies genome-scale metabolic network models. Paired Bray-Curtis distance between baseline and follow-up time points was significantly different for UC patients treated with anti-TNF antibodies. Longitudinal changes in taxa composition at phylum level showed a significant decrease of Proteobacteria and an increase of Bacteroidetes in CD patients responding to both therapies. At family level, Lactobacilli were associated with persistent disease and Bacteroides abundance with remission in CD. In-silico simulations of microbial metabolite exchange predicted a 1.7-fold higher butyrate production capacity of patients in remission compared with patients without remission [p = 0.041]. In this model, the difference in butyrate production between patients in remission and patients without remission was most pronounced in the CD group treated with AZA [p = 0.008]. In-silico simulation identifies microbial butyrate synthesis predictive of therapeutic efficacy in IBD.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
The microbial ecosystem seems to be an important player for therapeutic intervenption in inflammatory bowel disease [IBD]. We assessed longitudinal microbiome changes in IBD patients undergoing therapy with either azathioprine [AZA] or anti-tumour necrosis factor [anti-TNF] antibodies. We predicted the metabolic microbial community exchange and linked it to clinical outcome.
METHODS
METHODS
Faecal and blood samples were collected from 65 IBD patients at baseline and after 12 and 30 weeks on therapy. Clinical remission was defined as Crohn's Disease Activity Index [CDAI] < 150 in Crohn´s disease [CD], partial Mayo score <2 in ulcerative colitis [UC], and faecal calprotectin values <150 µg/g and C-reactive protein <5 mg/dl. 16S rRNA amplicon sequencing was performed. To predict microbial community metabolic processes, we constructed multispecies genome-scale metabolic network models.
RESULTS
RESULTS
Paired Bray-Curtis distance between baseline and follow-up time points was significantly different for UC patients treated with anti-TNF antibodies. Longitudinal changes in taxa composition at phylum level showed a significant decrease of Proteobacteria and an increase of Bacteroidetes in CD patients responding to both therapies. At family level, Lactobacilli were associated with persistent disease and Bacteroides abundance with remission in CD. In-silico simulations of microbial metabolite exchange predicted a 1.7-fold higher butyrate production capacity of patients in remission compared with patients without remission [p = 0.041]. In this model, the difference in butyrate production between patients in remission and patients without remission was most pronounced in the CD group treated with AZA [p = 0.008].
CONCLUSIONS
CONCLUSIONS
In-silico simulation identifies microbial butyrate synthesis predictive of therapeutic efficacy in IBD.
Identifiants
pubmed: 32687146
pii: 5873836
doi: 10.1093/ecco-jcc/jjaa152
doi:
Substances chimiques
Antimetabolites
0
Butyrates
0
Tumor Necrosis Factor Inhibitors
0
Azathioprine
MRK240IY2L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
88-98Informations 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.