期刊
JOURNAL OF CROHNS & COLITIS
卷 15, 期 1, 页码 88-98出版社
OXFORD UNIV PRESS
DOI: 10.1093/ecco-jcc/jjaa152
关键词
Azathioprine; IBD; microbiota
资金
- excellence initiative VASCage [Centre for Promoting Vascular Health in the Ageing Community], an R&D K-Centre [COMET program-Competence Centers for Excellent Technologies] - Austrian Ministry for Transport, Innovation and Technology
- Austrian Ministry for Digital and Economic Affairs
- federal state Tyrol
- federal state Salzburg
- federal state Vienna
- BMBF-initiative E:med [Try-IBD] [01ZX1915A]
- DFG [RU 5042]
- Austrian Science Fund [FWF] [P. 33070-B]
- Christian Doppler Research Association
- Austrian Federal Ministry of Science, Research, and Economy
- National Foundation for Research, Technology, and Development
Longitudinal microbiome changes in IBD patients undergoing therapy with either azathioprine or anti-TNF antibodies showed significant alterations in microbial community composition under specific therapies, with a notable increase in butyrate production capacity in patients in remission.
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 mu g/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.
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