Cells. 2023 Jul 27;12(15):1953. doi: 10.3390/cells12151953.

Federica Di Vincenzo ^1 2, Ylenia Yadid ², Valentina Petito ¹, Valeria Emoli ², Letizia Masi ¹, Daniela Gerovska ³, Marcos Jesus Araúzo-Bravo ^3 4 5, Antonio Gasbarrini ^1 2, Birgitte Regenberg ⁶, Franco Scaldaferri ^1 2

Author information

¹IBD Unit, Centro di Malattie dell'Apparato Digerente (CeMAD), Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, 00168 Rome, Italy.

²Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.

³Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, Calle Doctor Begiristain s/n, 20014 San Sebastian, Spain.

⁴IKERBASQUE, Basque Foundation for Science, Calle María Díaz Harokoa 3, 48013 Bilbao, Spain.

⁵Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of Basque Country (UPV/EHU), 48940 Leioa, Spain.

⁶Section for Ecology and Evolution, Department of Biology, University of Copenhagen, Universitetsparken 13, Room 426, DK-2100 Copenhagen, Denmark.

Abstract

Inflammatory bowel diseases (IBD), including Crohn's Disease (CD) and Ulcerative Colitis (UC) are chronic multifactorial disorders which affect the gastrointestinal tract with variable extent. Despite extensive research, their etiology and exact pathogenesis are still unknown. Cell-free DNAs (cfDNAs) are defined as any DNA fragments which are free from the origin cell and able to circulate into the bloodstream with or without microvescicles. CfDNAs are now being increasingly studied in different human diseases, like cancer or inflammatory diseases. However, to date it is unclear how IBD etiology is linked to cfDNAs in plasma. Extrachromosomal circular DNA (eccDNA) are non-plasmidic, nuclear, circular and closed DNA molecules found in all eukaryotes tested. CfDNAs appear to play an important role in autoimmune diseases, inflammatory processes, and cancer; recently, interest has also grown in IBD, and their role in the pathogenesis of IBD has been suggested. We now suggest that eccDNAs also play a role in IBD. In this review, we have comprehensively collected available knowledge in literature regarding cfDNA, eccDNA, and structures involving them such as neutrophil extracellular traps and exosomes, and their role in IBD. Finally, we focused on old and novel potential molecular therapies and drug delivery systems, such as nanoparticles, for IBD treatment.