Kirk Daniel, Louca Panayiotis, Attaye Ilias, Zhang Xinyuan, Wong Kari E, Michelotti Gregory A, Falchi Mario, Valdes Ana M, Williams Frances M K, Menni Cristina
Department of Twin Research & Genetic Epidemiology, King's College London, London SE1 7EH, UK.
Amsterdam Cardiovascular Sciences, Diabetes & Metabolism, 1105 AZ Amsterdam, The Netherlands.
Metabolites. 2025 Feb 12;15(2):121. doi: 10.3390/metabo15020121.
: Irritable bowel syndrome (IBS) is a complex disorder affecting 10% of the global population, but the underlying mechanisms remain poorly understood. By integrating multifluid metabolomics, we aimed to identify metabolite markers of IBS in a large population-based cohort. : We included individuals from TwinsUK with and without IBS, ascertained using the Rome III criteria, and analysed serum (232 cases, 1707 controls), urine (185 cases, 1341 controls), and stool (186 cases, 1284 controls) metabolites (Metabolon Inc.). : After adjusting for covariates, and multiple testing, 44 unique metabolites (25 novel) were associated with IBS, including lipids, amino acids, and xenobiotics. Androsterone sulphate, a sulfated steroid hormone precursor, was associated with lower odds of IBS in both urine (0.69 [95% confidence interval = 0.56-0.85], = 2.34 × 10) and serum (0.75 [0.63-0.90], = 1.54 × 10. Moreover, suberate (C8-DC) was associated with higher odds of IBS in serum (1.36 [1.15-1.61]; = 1.84 × 10) and lower odds of IBS in stool (0.76 [0.63-0.91]; = 2.30 × 10). On the contrary, 32 metabolites appeared to be fluid-specific, including indole, 13-HODE + 9-HODE, pterin, bilirubin (E,Z or Z,Z), and urolithin. The remaining 10 metabolites were associated with IBS in one fluid with suggestive evidence ( < 0.05) in another fluid. Finally, we identified androgenic signalling, dicarboxylates, haemoglobin, and porphyrin metabolism to be significantly over-represented in individuals with IBS compared to controls. : Our results highlight the utility of a multi-fluid approach in IBS research, revealing distinct metabolic signatures across biofluids.
肠易激综合征（IBS）是一种复杂的疾病，影响着全球10%的人口，但其潜在机制仍知之甚少。通过整合多流体代谢组学，我们旨在在一个基于人群的大型队列中确定IBS的代谢物标志物。
我们纳入了来自英国双胞胎队列研究中符合和不符合罗马III标准的IBS个体，并分析了血清（232例病例，1707例对照）、尿液（185例病例，1341例对照）和粪便（186例病例，1284例对照）中的代谢物（Metabolon公司）。
在校正协变量和多重检验后，44种独特的代谢物（25种为新发现的）与IBS相关，包括脂质、氨基酸和外源性物质。硫酸雄酮，一种硫酸化的类固醇激素前体，在尿液（比值比=0.69[95%置信区间=0.56-0.85]，P=2.34×10⁻³）和血清（比值比=0.75[0.63-0.90]，P=1.54×10⁻²）中均与IBS的较低发病几率相关。此外，辛二酸（C8-DC）在血清中与IBS的较高发病几率相关（比值比=1.36[1.15-1.61]；P=1.84×10⁻³），而在粪便中与IBS的较低发病几率相关（比值比=0.76[0.63-0.91]；P=2.30×10⁻²）。相反，32种代谢物似乎具有流体特异性，包括吲哚、13-羟基十八碳二烯酸+9-羟基十八碳二烯酸、蝶呤、胆红素（E,Z或Z,Z）和尿石素。其余10种代谢物在一种流体中与IBS相关，在另一种流体中有提示性证据（P<0.05）。最后，我们确定雄激素信号传导、二羧酸、血红蛋白和卟啉代谢在IBS患者中与对照组相比显著富集。
我们的结果突出了多流体方法在IBS研究中的实用性，揭示了不同生物流体中的独特代谢特征。
