Moe Øystein K, Gao Qian, Geng Dawei, Jensen Einar, Goll Rasmus, Nestegard Oddmund, Gundersen Mona D, Florholmen Jon R, Moritz T
Research Group of Gastroenterology and Nutrition, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
Department of Gastroenterology, Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
BMC Gastroenterol. 2025 May 20;25(1):389. doi: 10.1186/s12876-025-03944-6.
Mechanisms causing non-response to biological agents in IBD remain to be fully understood. Thus, we aimed to characterize the lipid profile in treatment refractory non-immunogenic patients with adequate trough-levels.
Patients with IBD refractory to treatment with anti-tumour necrosis factor or vedolizumab were included from a Norwegian translation study. Mucosal lipid profiles were compared to reference groups. The reference groups included treatment naïve IBD patients with moderate to severe disease at debut who later achieved remission or response on antiTNFs, IBD patients treated to remission with biological agents, and healthy normal controls. Lipidomics analyses were performed on mucosal biopsies. Statistical analyses of lipid levels were carried out using generalized least squares. Lipidomics data were log2-transformed and auto-scaled before analysis. P-values were adjusted using Benjamini- Hochberg procedure to control the false discovery rate (FDR).
Proinflammatory lipids including ceramides and sphingomyelins and protective lipids like glycerophosphocholines and glycerophosphoethanolamines were significantly decreased in treatment refractory UC patients compared to treatment naïve UC patients with moderate to severe disease. Compared to controls, major changes in ceramides (Cer), hexosyl ceramides (HexCer), sphingomyelins (SM), glycerophosphocholines (PC), glycerophosphoethanolamines (PE) and glycerophosphoserines (PS) were observed in treatment refractory UC patients. Refractory CD patients showed minor changes compared to the other CD-groups. There were no significant differences in the mucosal lipid levels of IBD patients in remission compared to normal controls.
The mucosal lipid profile of treatment refractory UC shows marked shifts compared to treatment naïve UC at debut with moderate to severe inflammation. These are novel findings which possibly indicate dynamic processes of long-standing mucosal inflammation. The mucosal lipid profile of IBD patients in remission seems to be similar to the normal state.
炎症性肠病（IBD）中导致对生物制剂无反应的机制仍有待充分了解。因此，我们旨在对治疗难治性、低谷水平充足的非免疫原性患者的脂质谱进行特征分析。
从一项挪威翻译研究中纳入对抗肿瘤坏死因子或维多珠单抗治疗难治的IBD患者。将黏膜脂质谱与参照组进行比较。参照组包括初发时患有中度至重度疾病、后来对抗肿瘤坏死因子实现缓解或反应的未接受过治疗的IBD患者、经生物制剂治疗至缓解的IBD患者以及健康正常对照。对黏膜活检组织进行脂质组学分析。使用广义最小二乘法对脂质水平进行统计分析。脂质组学数据在分析前进行log2转换和自动缩放。使用Benjamini-Hochberg程序调整P值以控制错误发现率（FDR）。
与初发时患有中度至重度疾病的未接受过治疗的溃疡性结肠炎（UC）患者相比，治疗难治性UC患者中包括神经酰胺和鞘磷脂在内的促炎脂质以及如甘油磷酰胆碱和甘油磷酰乙醇胺等保护性脂质显著减少。与对照组相比，在治疗难治性UC患者中观察到神经酰胺（Cer）、己糖神经酰胺（HexCer）、鞘磷脂（SM）、甘油磷酰胆碱（PC）、甘油磷酰乙醇胺（PE）和甘油磷酰丝氨酸（PS）有重大变化。与其他克罗恩病（CD）组相比，难治性CD患者变化较小。与正常对照相比，处于缓解期IBD患者的黏膜脂质水平无显著差异。
与初发时伴有中度至重度炎症的未接受过治疗的UC相比，治疗难治性UC的黏膜脂质谱有明显变化。这些是新发现，可能表明长期黏膜炎症的动态过程。处于缓解期的IBD患者的黏膜脂质谱似乎与正常状态相似。
