Journal article
Metabonomics and the gut microbiome associated with primary response to Anti-TNF therapy in Crohn’s Disease
Journal of Crohn's and Colitis, Vol.14(8), pp.1090-1102
2020
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.
Details
- Title
- Metabonomics and the gut microbiome associated with primary response to Anti-TNF therapy in Crohn’s Disease
- Authors/Creators
- N.S. Ding (Author/Creator)J.A.K. McDonald (Author/Creator)A. Perdones-Montero (Author/Creator)D.N. Rees (Author/Creator)S.O. Adegbola (Author/Creator)R. Misra (Author/Creator)P. Hendy (Author/Creator)L. Penez (Author/Creator)J.R. Marchesi (Author/Creator)E. Holmes (Author/Creator)M.H. Sarafian (Author/Creator)A.L. Hart (Author/Creator)
- Publication Details
- Journal of Crohn's and Colitis, Vol.14(8), pp.1090-1102
- Publisher
- Elsevier B.V.
- Identifiers
- 991005543920407891
- Copyright
- © 2020 Oxford University Press
- Murdoch Affiliation
- Health Futures Institute
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
111 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.120 Inflammatory Bowel Diseases & Infections
- 1.120.139 Inflammatory Bowel Disease
- Web Of Science research areas
- Gastroenterology & Hepatology
- ESI research areas
- Clinical Medicine