Metabonomics and the gut microbiome associated with primary response to Anti-TNF therapy in Crohn’s Disease
Ding, N.S., McDonald, J.A.K., Perdones-Montero, A., Rees, D.N., Adegbola, S.O., Misra, R., Hendy, P., Penez, L., Marchesi, J.R., Holmes, E., Sarafian, M.H. and Hart, A.L. (2020) Metabonomics and the gut microbiome associated with primary response to Anti-TNF therapy in Crohn’s Disease. Journal of Crohn's and Colitis, 14 (8). pp. 1090-1102.
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Abstract
Background and Aims
Anti-tumour necrosis factor [anti-TNF] therapy is indicated for treatment of moderate to severe inflammatory bowel disease [IBD], but has a primary non-response rate of around 30%. We aim to use metabonomic and metataxonomic profiling to identify predictive biomarkers of anti-TNF response in Crohn’s disease.
Methods
Patients with luminal Crohn’s disease, commencing anti-TNF therapy, were recruited with urine, faeces, and serum samples being collected at baseline and 3-monthly. Primary response was defined according to a combination of clinical and objective markers of inflammation. Samples were measured using three UPLC-MS assays: lipid, bile acid, and Hydrophillic Interaction Liquid Chromatography [HILIC] profiling with 16S rRNA gene sequencing of faeces.
Results
Samples were collected from 76 Crohn’s disease patients who were anti-TNF naïve and from 13 healthy controls. There were 11 responders, 37 non-responders, and 28 partial responders in anti-TNF-treated Crohn’s patients. Histidine and cysteine were identified as biomarkers of response from polar metabolite profiling [HILIC] of serum and urine. Lipid profiling of serum and faeces found phosphocholines, ceramides, sphingomyelins, and triglycerides, and bile acid profiling identified primary bile acids to be associated with non-response to anti-TNF therapy, with higher levels of phase 2 conjugates in non-responders. Receiver operating curves for treatment response demonstrated 0.94 +/ -0.10 [faecal lipid], 0.81 +/- 0.17 [faecal bile acid], and 0.74 +/- 0.15 [serum bile acid] predictive ability for anti-TNF response in Crohn’s disease.
Conclusions
This prospective, longitudinal cohort study of metabonomic and 16S rRNA gene sequencing analysis demonstrates that a range of metabolic biomarkers involving lipid, bile acid, and amino acid pathways may contribute to prediction of response to anti-TNF therapy in Crohn’s disease.
Item Type: | Journal Article |
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Murdoch Affiliation: | Health Futures Institute |
Publisher: | Elsevier B.V. |
Copyright: | © 2020 Oxford University Press |
URI: | http://researchrepository.murdoch.edu.au/id/eprint/57717 |
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