Exposome, Oxidative Stress and Inflammation in persons with multiple sclerosis: The EXPOSITION study protocol

Maria Cristina Monti¹Rachele De Giuseppe^2*Gloria Bertoli³Mulubirhan Assefa Alemayohu¹Ghanya Al-Naqeb²Elena Ballante⁴Roberto Bergamaschi⁴Tania Camboni⁵Camilla Ceccarani⁵Chiara Ceriani⁶Elena Colombo⁴Clarissa Consolandi⁵Francesca Costabile⁷Stefano Decesari⁸Francesca Gallivanone⁶Bruno Giovanni Galuzzi⁶Matteo Gastaldi⁴Clarissa Gervasoni⁶Simona Gugiatti⁹Teresa Itri⁴Aliki Kalmpourtzidou⁹Tony Christian LANDI⁸Aurora Lanzotti⁶Alessia Lo Dico⁶Federica Loperfido⁹Beatrice Maccarini⁹Antonio Mazza¹⁰Cristina Montomoli¹Enrico Oddone^11,12Noemi Paulin¹¹Chiara Pellizzer⁶Roberta Pernetti¹¹Anna Scarabotto⁴Francesca Sellaro¹¹Marco Severgnini⁵Donato Summa¹⁰Gemine Vivone¹⁰Danilo Porro⁶Hellas Cena^13,9Eleonora Tavazzi⁴

• ¹Unit of Biostatistics and Clinical Epidemiology, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy., Pavia, Italy
• ²Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy
• ³Istituto di Bioimmagini e Sistemi Biologici Complessi (IBSBC) - National Research Council (CNR), Segrate, 20054 Milano, Italy., Milano, Italy
• ⁴IRCCS Mondino Foundation, Pavia, Italy, Pavia, Italy
• ⁵Institute for Biomedical Technologies, National Research Council (ITB-CNR), Via F.lli Cervi 93, 20054, Segrate, Italy, Milano, Italy
• ⁶Istituto di Bioimmagini e Sistemi Biologici Complessi (IBSBC) - National Research Council (CNR), Segrate, 20054 Milan, Italy., Milano, Italy
• ⁷Institute of Atmospheric Sciences and Climate - Italian National Research Council (ISAC - CNR), Via Fosso del Cavaliere, 00133, Rome, Italy, Roma, Italy
• ⁸Institute for Atmospheric Sciences and Climate, National Research Council of Italy, via Gobetti 101, 40129 Bologna, Italy, Bologna, Italy
• ⁹Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy., Pavia, Italy
• ¹⁰Institute of Methodologies for Environmental Analysis, CNR-IMAA, Tito Scalo, 85050, Italy, Potenza, Italy
• ¹¹Unit of Occupational Medicine, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy, Pavia, Italy
• ¹²Hospital Operative Occupational Medicine Unit, ICS Maugeri IRCCS, Pavia, Italy., Pavia, Italy
• ¹³Unit of Clinical Nutrition, ICS Maugeri IRCCS, Pavia, Italy, Pavia, Italy

The exposome represents the totality of external and internal exposures an individual encounters throughout life and plays a critical role in developing many chronic diseases, including multiple sclerosis (MS). MS is a multifactorial disease influenced by both genetic and environmental factors. The EXPOSITION study (registered on www.clinicaltrials.gov, NCT06325358) aims to investigate the association between environmental exposures (external exposome) and biological markers of oxidative stress and inflammation (internal exposome) in people with MS. This cross-sectional study will involve 200 individuals with MS, assessed for lifestyle and occupational variables and biological markers, including circulating microRNAs, neurofilament light chains, pro-and anti-inflammatory cytokines, and gut/nasal microbiota composition. The study will use advanced statistical models, such as generalised linear models and multivariate analyses, to assess associations between external exposures and biological outcomes. By integrating both environmental and biological factors, this research aims to deepen our understanding of MS mechanisms, providing insights that could lead to targeted interventions, personalised therapies, and public health strategies to mitigate MS progression.