Microbial Butyrate Synthesis Indicates Therapeutic Efficacy of Azathioprine in IBD Patients.

Publisher: Oxford University Press Country of Publication: England NLM ID: 101318676 Publication Model: Print Cited Medium: Internet ISSN: 1876-4479 (Electronic) Linking ISSN: 18739946 NLM ISO Abbreviation: J Crohns Colitis Subsets: MEDLINE

Publication: 2015- : Oxford : Oxford University Press
Original Publication: Amsterdam : Elsevier Science

Azathioprine*/administration & dosage ; Azathioprine*/adverse effects ; Biosynthetic Pathways*/drug effects ; Biosynthetic Pathways*/genetics ; Colitis, Ulcerative*/drug therapy ; Colitis, Ulcerative*/metabolism ; Colitis, Ulcerative*/microbiology ; Crohn Disease*/drug therapy ; Crohn Disease*/metabolism ; Crohn Disease*/microbiology ; Gastrointestinal Microbiome*/drug effects ; Gastrointestinal Microbiome*/physiology ; Tumor Necrosis Factor Inhibitors*/administration & dosage ; Tumor Necrosis Factor Inhibitors*/adverse effects; Butyrates/*metabolism; Adult ; Antimetabolites/administration & dosage ; Antimetabolites/adverse effects ; Bacteroidetes/isolation & purification ; Bacteroidetes/metabolism ; Computer Simulation ; Correlation of Data ; Female ; Humans ; Male ; Middle Aged ; Proteobacteria/isolation & purification ; Proteobacteria/metabolism ; Remission Induction ; Treatment Outcome

Background and Aims: 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: 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: 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: In-silico simulation identifies microbial butyrate synthesis predictive of therapeutic efficacy in IBD.
(© 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.)

Keywords: Azathioprine; IBD; microbiota

0 (Antimetabolites)
0 (Butyrates)
0 (Tumor Necrosis Factor Inhibitors)
MRK240IY2L (Azathioprine)

Date Created: 20200721 Date Completed: 20211013 Latest Revision: 20211013

20240829

10.1093/ecco-jcc/jjaa152

32687146