Elevation of serum pyruvate kinase M2 (PKM2) in IBD and its relationship to IBD indices

Objectives: 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. Design and methods: 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. Results: 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 (500 ng/mL) significantly increased PKM2 expression in vitro, which was significantly suppressed by an anti-inflammatory flaxseed bioactive agent. Conclusion: 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.