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 who were anti-TNF naïve and 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 while 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.

中文翻译：

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代谢组学和肠道微生物组与克罗恩病抗TNF治疗的主要反应相关。

背景和目的抗肿瘤坏死因子（anti-TNF）治疗被指定用于治疗中度至重度炎症性肠病（IBD），但主要无反应率约为30％。我们旨在利用代谢组学和分类学分析来鉴定克罗恩病中抗TNF反应的预测生物标志物。方法招募开始抗TNF治疗的管腔克罗恩氏病患者，并于基线和每月3个月收集尿液，粪便和血清样本。根据炎症的临床和客观指标的组合定义主要反应。使用三种UPLC-MS测定法测量样品。粪便中16S rRNA基因测序的脂质，胆汁酸和亲水相互作用液相色谱（HILIC）分析 结果从76个克罗恩州收集了样品 曾接受过抗TNF治疗的患者和13名健康对照者。抗TNF治疗的克罗恩病患者中有11名反应者，37名无反应者和28名部分反应者。组氨酸和半胱氨酸被鉴定为血清和尿液中极性代谢物谱（HILIC）应答的生物标志物。血清和粪便的脂质谱分析发现了磷酸胆碱，神经酰胺，鞘磷脂和甘油三酸酯，而胆汁酸谱分析则发现原发性胆汁酸与抗TNF治疗无反应相关，无反应者中2相缀合物水平较高。接受者的治疗反应曲线表明克罗恩病抗TNF反应的预测能力为0.94 +/- 0.10（粪便脂质），0.81 +/- 0.17（粪便胆汁酸）和0.74 +/- 0.15（血清胆汁酸）。结论这个前瞻性的观点