Stenosing Crohn’s disease patients display gut autophagy/oxidative stress imbalance
Abstract In this pilot study, we assessed the role of autophagy in Crohn’s Disease (CD), particularly in patients with a stenosing phenotype. Through the analysis of biopsied specimens from 36 patients, including 11 controls and 25 CD patients, categorized into inflammatory and stenosing groups, we...
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Nature Portfolio
2024-11-01
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| Online Access: | https://doi.org/10.1038/s41598-024-79308-z |
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| author | Leonardo Schirone Maria Carla Di Paolo Daniele Vecchio Cristina Nocella Alessandra D’Amico Riccardo Urgesi Lorella Pallotta Gianfranco Fanello Giuseppe Villotti Maria Giovanna Graziani Mariangela Peruzzi Elena De Falco Roberto Carnevale Sebastiano Sciarretta Giacomo Frati Cristiano Pagnini |
| author_facet | Leonardo Schirone Maria Carla Di Paolo Daniele Vecchio Cristina Nocella Alessandra D’Amico Riccardo Urgesi Lorella Pallotta Gianfranco Fanello Giuseppe Villotti Maria Giovanna Graziani Mariangela Peruzzi Elena De Falco Roberto Carnevale Sebastiano Sciarretta Giacomo Frati Cristiano Pagnini |
| author_sort | Leonardo Schirone |
| collection | DOAJ |
| description | Abstract In this pilot study, we assessed the role of autophagy in Crohn’s Disease (CD), particularly in patients with a stenosing phenotype. Through the analysis of biopsied specimens from 36 patients, including 11 controls and 25 CD patients, categorized into inflammatory and stenosing groups, we identified a significant reduction in the autophagosomal marker Lc3b-II in patients with active inflammation and stenosis. This was paralleled by an increase in oxidative stress markers, including sNOX2-dp and H2O2, and a decrease in the antioxidant capacity measured by HBA, suggesting an imbalance in autophagy and oxidative stress mechanisms. Additionally, our findings show a correlation between autophagy markers and oxidative stress levels, indicating that autophagy dysfunction may play a pivotal role in CD and in the progression of a stenosing disease phenotype, by failing to eliminate detrimental molecules and pathogenic bacteria, thereby promoting fibrosis. This study is the first to demonstrate in vivo autophagy inhibition in stenosing CD patients and suggests that stimulating autophagic processes could offer a new avenue for the prevention and treatment of intestinal fibrosis in CD. Our results highlight the importance of exploring the interactions between autophagy, the fibrotic process, and the inflammatory cascade, opening avenues for potential therapeutic interventions in CD management. |
| format | Article |
| id | doaj-art-3aeed55b3fd74bc9b75a7bbd123b9beb |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-3aeed55b3fd74bc9b75a7bbd123b9beb2024-11-10T12:24:00ZengNature PortfolioScientific Reports2045-23222024-11-011411710.1038/s41598-024-79308-zStenosing Crohn’s disease patients display gut autophagy/oxidative stress imbalanceLeonardo Schirone0Maria Carla Di Paolo1Daniele Vecchio2Cristina Nocella3Alessandra D’Amico4Riccardo Urgesi5Lorella Pallotta6Gianfranco Fanello7Giuseppe Villotti8Maria Giovanna Graziani9Mariangela Peruzzi10Elena De Falco11Roberto Carnevale12Sebastiano Sciarretta13Giacomo Frati14Cristiano Pagnini15IRCCS NeuromedS. Giovanni Addolorata HospitalDepartment of Medical and Surgical Sciences and Biotechnologies, Sapienza University of RomeDepartment of Clinical Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of RomeDepartment of Medical and Surgical Sciences and Biotechnologies, Sapienza University of RomeS. Giovanni Addolorata HospitalS. Giovanni Addolorata HospitalS. Giovanni Addolorata HospitalS. Giovanni Addolorata HospitalS. Giovanni Addolorata HospitalDepartment of Clinical Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of RomeDepartment of Medical and Surgical Sciences and Biotechnologies, Sapienza University of RomeIRCCS NeuromedIRCCS NeuromedIRCCS NeuromedS. Giovanni Addolorata HospitalAbstract In this pilot study, we assessed the role of autophagy in Crohn’s Disease (CD), particularly in patients with a stenosing phenotype. Through the analysis of biopsied specimens from 36 patients, including 11 controls and 25 CD patients, categorized into inflammatory and stenosing groups, we identified a significant reduction in the autophagosomal marker Lc3b-II in patients with active inflammation and stenosis. This was paralleled by an increase in oxidative stress markers, including sNOX2-dp and H2O2, and a decrease in the antioxidant capacity measured by HBA, suggesting an imbalance in autophagy and oxidative stress mechanisms. Additionally, our findings show a correlation between autophagy markers and oxidative stress levels, indicating that autophagy dysfunction may play a pivotal role in CD and in the progression of a stenosing disease phenotype, by failing to eliminate detrimental molecules and pathogenic bacteria, thereby promoting fibrosis. This study is the first to demonstrate in vivo autophagy inhibition in stenosing CD patients and suggests that stimulating autophagic processes could offer a new avenue for the prevention and treatment of intestinal fibrosis in CD. Our results highlight the importance of exploring the interactions between autophagy, the fibrotic process, and the inflammatory cascade, opening avenues for potential therapeutic interventions in CD management.https://doi.org/10.1038/s41598-024-79308-zInflammatory Bowel Disease (IBD)Autophagic DysregulationReactive Oxygen Species (ROS)Fibrostenotic ComplicationsRedox Homeostasis |
| spellingShingle | Leonardo Schirone Maria Carla Di Paolo Daniele Vecchio Cristina Nocella Alessandra D’Amico Riccardo Urgesi Lorella Pallotta Gianfranco Fanello Giuseppe Villotti Maria Giovanna Graziani Mariangela Peruzzi Elena De Falco Roberto Carnevale Sebastiano Sciarretta Giacomo Frati Cristiano Pagnini Stenosing Crohn’s disease patients display gut autophagy/oxidative stress imbalance Scientific Reports Inflammatory Bowel Disease (IBD) Autophagic Dysregulation Reactive Oxygen Species (ROS) Fibrostenotic Complications Redox Homeostasis |
| title | Stenosing Crohn’s disease patients display gut autophagy/oxidative stress imbalance |
| title_full | Stenosing Crohn’s disease patients display gut autophagy/oxidative stress imbalance |
| title_fullStr | Stenosing Crohn’s disease patients display gut autophagy/oxidative stress imbalance |
| title_full_unstemmed | Stenosing Crohn’s disease patients display gut autophagy/oxidative stress imbalance |
| title_short | Stenosing Crohn’s disease patients display gut autophagy/oxidative stress imbalance |
| title_sort | stenosing crohn s disease patients display gut autophagy oxidative stress imbalance |
| topic | Inflammatory Bowel Disease (IBD) Autophagic Dysregulation Reactive Oxygen Species (ROS) Fibrostenotic Complications Redox Homeostasis |
| url | https://doi.org/10.1038/s41598-024-79308-z |
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