Association of Gut Microbiome and Dipeptidyl Peptidase 4 in Immune-Mediated Inflammatory Bowel Disease: A Rapid Literature Review.

Immune-mediated inflammatory diseases (IMIDs) are characterized by dysregulated immune responses and chronic tissue inflammation. In the setting of inflammatory bowel disease (IBD), dipeptidyl peptidase 4 (DPP4) and gut microorganisms have been proved to interplay, potentially influenced by dietary factors. This rapid review aimed to study the DPP4-gut microbiome link in IBD. A search across five databases and two gray literature sources identified seven relevant studies reporting data on DPP4 and gut microbiome in patients with IBD-related IMIDs or in vitro or in vivo models: one cross-sectional, one in vitro, and five in vivo studies. The findings revealed a significant impact of DPP4 and its substrates, i.e., glucagon-like peptide-1/2 (GLP-1/2), on the composition of gut microbiome and on the development of dysbiosis. Increased DPP4 activity is associated with decreased GLP-1/2; increased pathogenic bacterial phyla such as Actinobacteria, Bacteroidetes, Deferribacteres, Firmicutes, Fusobacteriota, Proteobacteria, and Verrucomicrobia; and decreased alpha diversity of beneficial gut microbes, including , , and families and short-chain fatty acid-producing bacteria like and spp., with exacerbation of intestinal inflammation. This overview revealed that understanding the DPP4-gut microbiome association is critical for the development of DPP4-targeted therapeutic strategies to guarantee gut microbiome balance and modulation of immune response in IBD.