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Metabonomics and the Gut Microbiome Associated With Primary Response to Anti-TNF Therapy in Crohn’s Disease

克罗恩病 医学 炎症性肠病 胃肠病学 粪便 胆汁酸 内科学 微生物群 肿瘤坏死因子α 溃疡性结肠炎 疾病 生物 生物信息学 微生物学
作者
Nik Sheng Ding,Julie A. K. McDonald,Alvaro Perdones‐Montero,Douglas Rees,S Adegbola,Ravi Misra,Philip Hendy,L Penez,Julian R. Marchesi,Elaine Holmes,Magali Sarafian,Ailsa Hart
出处
期刊:Journal of Crohn's and Colitis [Oxford University Press]
卷期号:14 (8): 1090-1102 被引量:53
标识
DOI:10.1093/ecco-jcc/jjaa039
摘要

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. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast
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