Almousa Ahmed A, Morris Marc, Fowler Sharyle, Jones Jennifer, Alcorn Jane
Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan, Canada.
Department of Gastroenterology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Clin Biochem. 2018 Mar;53:19-24. doi: 10.1016/j.clinbiochem.2017.12.007. Epub 2017 Dec 19.
Endoscopy remains the gold standard to diagnose and evaluate inflammatory bowel disease (IBD) activity. Current biomarkers or their combinations cannot adequately predict IBD risk, diagnosis, progression or relapse, and response to therapy. Pyruvate kinase M2 (PKM2) is emerging as a significant mediator of the inflammatory process. We aimed to assess levels of serum PKM2 in healthy and newly diagnosed IBD patients and its relationship with IBD indices and microbiota changes.
IBD serum samples from newly diagnosed patients were collected and analyzed using a PKM2-ELISA and correlated with disease activity scores, IBD disease type, and intestinal microbiota. Furthermore, we tested the genetic and protein expression of PKM2 in an in vitro intestinal cell model of inflammation.
Serum PKM2 levels were 6-fold higher in IBD patients compared to healthy controls, with no sensitivity to disease phenotype (Crohn's Disease or Ulcerative Colitis) or localization of inflammation. Serum PKM2 had considerably less interindividual variability than established IBD fecal biomarkers. A positive Pearson correlation (r=0.6121) existed between serum PKM2 and Bacteroidetes fecal levels in Crohn's disease (CD), while a negative (r=-0.6128) correlation was observed with Actinobacteria fecal levels. Furthermore, LPS (500ng/mL) significantly increased PKM2 expression in vitro, which was significantly suppressed by an anti-inflammatory flaxseed bioactive agent.
Our data suggests PKM2 as a putative biomarker for IBD and the dysbiosis of microflora in CD. Investigations involving larger number of clinical patients are necessary to validate its use as a serum biomarker of IBD.
内镜检查仍是诊断和评估炎症性肠病（IBD）活动度的金标准。目前的生物标志物或其组合无法充分预测IBD风险、诊断、进展或复发以及对治疗的反应。丙酮酸激酶M2（PKM2）正成为炎症过程的重要介质。我们旨在评估健康人和新诊断的IBD患者血清PKM2水平及其与IBD指标和微生物群变化的关系。
收集新诊断患者的IBD血清样本，采用PKM2-ELISA进行分析，并与疾病活动评分、IBD疾病类型和肠道微生物群相关联。此外，我们在体外炎症性肠细胞模型中检测了PKM2的基因和蛋白表达。
与健康对照相比，IBD患者血清PKM2水平高6倍，对疾病表型（克罗恩病或溃疡性结肠炎）或炎症定位不敏感。血清PKM2的个体间变异性比既定的IBD粪便生物标志物小得多。克罗恩病（CD）患者血清PKM2与粪便拟杆菌水平呈正Pearson相关性（r=0.6121），而与粪便放线菌水平呈负相关性（r=-0.6128）。此外，脂多糖（500ng/mL）在体外显著增加PKM2表达，而一种抗炎亚麻籽生物活性剂可显著抑制该表达。
我们的数据表明PKM2是IBD和CD中微生物群失调的一种假定生物标志物。需要进行涉及更多临床患者的研究来验证其作为IBD血清生物标志物的用途。
