Extracellular Vesicle-Enclosed Oxidative Stress- and Inflammation-Related microRNAs as Potential Biomarkers of Vitamin D Responsivity: A Pilot Study on Inflammatory Bowel Disease Patients with or without COVID-19
Giorgia Ammirata,
Maddalena Arigoni,
Danilo Licastro,
Gian Paolo Caviglia,
Michela Disabato,
Ghania Zubair,
Cristina Bezzio,
Simone Saibeni,
Amedeo De Nicolò,
Jessica Cusato,
Alice Palermiti,
Alessandra Manca,
Emanuela Tolosano,
Stefano Cozzini,
Marcello Mancini,
Fiorella Altruda,
Antonio D’Avolio,
Davide Giuseppe Ribaldone,
Ugo Ala,
Sharmila Fagoonee
Affiliations
Giorgia Ammirata
Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Centre “Guido Tarone”, University of Turin, 10126 Turin, Italy
Maddalena Arigoni
Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Centre “Guido Tarone”, University of Turin, 10126 Turin, Italy
Danilo Licastro
AREA Science Park, Padriciano, 34149 Trieste, Italy
Gian Paolo Caviglia
Gastroenterology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
Michela Disabato
Gastroenterology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
Ghania Zubair
Department of Mathematics “Giuseppe Peano”, University of Turin, 10126 Turin, Italy
Cristina Bezzio
IBD Centre, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
Simone Saibeni
Gastroenterology Unit, Rho Hospital, ASST Rhodense, 20017 Milan, Italy
Amedeo De Nicolò
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, 10149 Turin, Italy
Jessica Cusato
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, 10149 Turin, Italy
Alice Palermiti
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, 10149 Turin, Italy
Alessandra Manca
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, 10149 Turin, Italy
Emanuela Tolosano
Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Centre “Guido Tarone”, University of Turin, 10126 Turin, Italy
Stefano Cozzini
AREA Science Park, Padriciano, 34149 Trieste, Italy
Marcello Mancini
Institute for Biostructure and Bioimaging, CNR, Via T. De Amicis 95, 80145 Naples, Italy
Fiorella Altruda
Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Centre “Guido Tarone”, University of Turin, 10126 Turin, Italy
Antonio D’Avolio
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, 10149 Turin, Italy
Davide Giuseppe Ribaldone
Gastroenterology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
Ugo Ala
Department of Veterinary Sciences, University of Turin, Grugliasco, 10095 Turin, Italy
Sharmila Fagoonee
Institute for Biostructure and Bioimaging, CNR, Molecular Biotechnology Centre “Guido Tarone”, 10126 Turin, Italy
The relationship between serum 25-hydroxyvitamin D (25(OH)D) levels, genomic response to vitamin D (Vit.D), and positivity to SARS-CoV-2 remains understudied. In this pilot study, during the follow-up of patients with Inflammatory Bowel Disease (IBD) and COVID-19, we investigated this issue by analyzing the molecular contents of serum extracellular vesicles (EVs) from six groups of IBD patients (n = 32), classified according to anti-SARS-CoV-2 status, 25(OH)D level, and Vit.D supplementation, by small RNA-seq. This analysis revealed differentially expressed miRNAs, PIWI-RNA, transfer RNA, small nucleolar RNAs, and protein-coding RNAs in the EVs obtained from these cohorts of IBD patients. Experimental validation evidenced a statistically significant increase in miR30d-5p, miR150-5p, Let-7f-5p, and Let-7a-5p in the anti-SARS-CoV-2-positive and low 25(OH)D and Vit.D supplemented groups with respect to the non-Vit.D supplemented group, indicating their responsiveness to Vit.D treatment. Bioinformatics analysis highlighted the regulation of these validated miRNAs by oxidative stress and inflammation, hallmarks of IBD and COVID-19. Our study reports an unprecedented panel of circulating EV-enclosed inflammation- and oxidative stress-related miRNAs, the potentiality of which, as biomarkers for Vit.D responsivity in IBD patients, needs to be explored in future studies on larger cohorts in order to allow clinicians to optimize current treatment strategies upon viral infection.
