The Role of Dipeptidyl Peptidase 4 as a Therapeutic Target and Serum Biomarker in Inflammatory Bowel Disease: A Systematic Review.

Background: The roles dipeptidyl peptidase 4 (DPP4), aminopeptidase N (APN), and their substrates in autoimmune diseases are being increasingly recognized. However, their significance in inflammatory bowel diseases (IBD) is not entirely understood. This systematic review aims to discuss the pathophysiological processes related to these ectopeptidases while comparing findings from preclinical and clinical settings.

Methods: This review was conducted according to the PRISMA guidelines. We performed a literature search in PubMed, SCOPUS, and Web of Science to identify all reports from inception until February 2020. The search included validated animal models of intestinal inflammation and studies in IBD patients. Quality assessment was performed using SYRCLE's risk of bias tool and CASP qualitative and cohort checklists.

Results: From the 45 included studies, 36 were performed in animal models and 12 in humans (3 reports included both). Overall, the methodological quality of preclinical studies was acceptable. In animal models, DPP4 and APN inhibition significantly improved intestinal inflammation.Glucagon-like peptide (GLP)-1 and GLP-2 analogs and GLP-2-relase-inducing drugs also showed significant benefits in recovery from inflammatory damage. A nonsignificant trend toward disease remission with the GLP-2 analog teduglutide was observed in the sole interventional human study. All human studies reported an inverse correlation between soluble DPP4/CD26 levels and disease severity, in accordance with the proposal of DPP4 as a biomarker for IBD.

Conclusions: The use of DPP4 inhibitors and analogs of its substrates has clear benefits in the treatment of experimentally induced intestinal inflammation. Further research is warranted to validate their potential diagnostic and therapeutic applications in IBD patients.