| Autor: |
D'Ambrosio A; Unit of Chemical-Physics Fundamentals in Chemical Engineering, Department of Science and Technology for Sustainable Development and One Health, University Campus Bio-Medico of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy., Altomare A; Department of Sciences and Technology of Sustainable Development and Human Health, Università Campus Biomedico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy.; Gastroenterology Research Unit, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy., Boscarino T; Unit of Chemical-Physics Fundamentals in Chemical Engineering, Department of Science and Technology for Sustainable Development and One Health, University Campus Bio-Medico of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy., Gori M; Gastroenterology Research Unit, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy.; Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), International Campus 'A. Buzzati-Traverso', Via E. Ramarini 32, Monterotondo Scalo, 00015 Rome, Italy., Balestrieri P; Gastroenterology Unit, Fondazione Policlinico Campus Bio-Medico di Roma, Via Alvaro del Portillo 200, 00128 Rome, Italy., Putignani L; Units of Microbiomics and Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio 4, 00165 Rome, Italy., Del Chierico F; Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio 4, 00165 Rome, Italy., Carotti S; Microscopic and Ultrastructural Anatomy Research Unit, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy., Cicala M; Gastroenterology Research Unit, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy.; Microscopic and Ultrastructural Anatomy Research Unit, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy., Guarino MPL; Gastroenterology Research Unit, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy.; Gastroenterology Unit, Fondazione Policlinico Campus Bio-Medico di Roma, Via Alvaro del Portillo 200, 00128 Rome, Italy., Piemonte V; Unit of Chemical-Physics Fundamentals in Chemical Engineering, Department of Science and Technology for Sustainable Development and One Health, University Campus Bio-Medico of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy. |
| Abstrakt: |
Growing evidence suggests that impaired gut permeability and gut microbiota alterations are involved in the pathogenesis of Inflammatory Bowel Diseases (IBDs), which include Ulcerative Colitis (UC) and Crohn's Disease (CD). Vedolizumab is an anti-α4β7 antibody approved for IBD treatment, used as the first treatment or second-line therapy when the first line results in inadequate effectiveness. The aim of this study is to develop a mathematical model capable of describing the pathophysiological mechanisms of Vedolizumab treatment in IBD patients. In particular, the relationship between drug concentration in the blood, colonic mucosal permeability and fecal microbiota composition was investigated and modeled to detect and predict trends in order to support and tailor Vedolizumab therapies. To pursue this aim, clinical data from a pilot study on a cluster of 11 IBD patients were analyzed. Enrolled patients underwent colonoscopy in three phases (before (t0), after 24 weeks of (t1) and after 52 weeks of (t2 ) Vedolizumab treatment) to collect mucosal biopsies for transepithelial electrical resistance (TEER) evaluation (permeability to ions), intestinal permeability measurement and histological analysis. Moreover, fecal samples were collected for the intestinal microbiota analysis at the three time points. The collected data were compared to those of 11 healthy subjects at t0, who underwent colonoscopy for screening surveillance, and used to implement a three-compartmental mathematical model (comprising central blood, peripheral blood and the intestine). The latter extends previous evidence from the literature, based on the regression of experimental data, to link drug concentration in the peripheral blood compartment with Roseburia abundance and intestinal permeability. The clinical data showed that Vedolizumab treatment leads to an increase in TEER and a reduction in intestinal permeability to a paracellular probe, improving tissue inflammation status. Microbiota analysis showed increasing values of Roseburia , albeit not statistically significant. This trend was adequately reproduced by the mathematical model, which offers a useful tool to describe the pathophysiological effects of Vedolizumab therapy on colonic mucosal permeability and fecal microbiota composition. The model's satisfactory predictive capabilities and simplicity shed light on the relationship between the drug, the microbiota and permeability and allow for its straightforward extension to diverse therapeutic conditions. |
