SOD mimics delivered to the gut using lactic acid bacteria mitigate the colitis symptoms in a mouse model of inflammatory bowel diseases.
Gabrielle Schanne, Amandine Vincent, Florian Chain, Pauline Ruffié, Célia Carbonne, Elodie Quévrain, Emilie Mathieu, Alice Balfourier, Luis G Bermúdez-Humarán, Philippe Langella, Sophie Thenet, Véronique Carrière, Nassim Hammoudi, Magali Svrcek, Sylvie Demignot, Philippe Seksik, Clotilde Policar, Nicolas Delsuc
Author Information
Gabrielle Schanne: Laboratoire Chimie Pysique et Chimie du Vivant, CPCV UMR8228, Département de Chimie, Ecole Normale Supérieure, PSL University, Sorbonne Université, CNRS, Paris, France.
Amandine Vincent: Laboratoire Chimie Pysique et Chimie du Vivant, CPCV UMR8228, Département de Chimie, Ecole Normale Supérieure, PSL University, Sorbonne Université, CNRS, Paris, France.
Florian Chain: Micalis Institute, Université Paris-Saclay, INRAE, AgroParisTech, Jouy-en-Josas, France.
Pauline Ruffié: Micalis Institute, Université Paris-Saclay, INRAE, AgroParisTech, Jouy-en-Josas, France.
Célia Carbonne: Micalis Institute, Université Paris-Saclay, INRAE, AgroParisTech, Jouy-en-Josas, France.
Elodie Quévrain: Laboratoire Chimie Pysique et Chimie du Vivant, CPCV UMR8228, Département de Chimie, Ecole Normale Supérieure, PSL University, Sorbonne Université, CNRS, Paris, France.
Emilie Mathieu: Laboratoire Chimie Pysique et Chimie du Vivant, CPCV UMR8228, Département de Chimie, Ecole Normale Supérieure, PSL University, Sorbonne Université, CNRS, Paris, France.
Alice Balfourier: Laboratoire Chimie Pysique et Chimie du Vivant, CPCV UMR8228, Département de Chimie, Ecole Normale Supérieure, PSL University, Sorbonne Université, CNRS, Paris, France.
Luis G Bermúdez-Humarán: Micalis Institute, Université Paris-Saclay, INRAE, AgroParisTech, Jouy-en-Josas, France.
Philippe Langella: Micalis Institute, Université Paris-Saclay, INRAE, AgroParisTech, Jouy-en-Josas, France.
Sophie Thenet: Centre de Recherche Saint Antoine, INSERM, UMRS 938, Microbiota, Intestine and Inflammation Team, Paris, France.
Véronique Carrière: Centre de Recherche Saint Antoine, INSERM, UMRS 938, Microbiota, Intestine and Inflammation Team, Paris, France.
Nassim Hammoudi: Department of Gastroenterology, Hôpital Saint-Louis, AP-HP, INSERM U1160, Paris, France.
Magali Svrcek: Centre de Recherche Saint Antoine, INSERM, UMRS 938, Microbiota, Intestine and Inflammation Team, Paris, France.
Sylvie Demignot: Centre de Recherche Saint Antoine, INSERM, UMRS 938, Microbiota, Intestine and Inflammation Team, Paris, France.
Philippe Seksik: Centre de Recherche Saint Antoine, INSERM, UMRS 938, Microbiota, Intestine and Inflammation Team, Paris, France.
Clotilde Policar: Laboratoire Chimie Pysique et Chimie du Vivant, CPCV UMR8228, Département de Chimie, Ecole Normale Supérieure, PSL University, Sorbonne Université, CNRS, Paris, France.
Nicolas Delsuc: Laboratoire Chimie Pysique et Chimie du Vivant, CPCV UMR8228, Département de Chimie, Ecole Normale Supérieure, PSL University, Sorbonne Université, CNRS, Paris, France.
Inflammatory bowel diseases (IBD), which include Crohn's disease and ulcerative colitis, represent a global health issue as a prevalence of 1% is expected in the western world by the end of this decade. These diseases are associated with a high oxidative stress that induces inflammatory pathways and severely damages gut tissues. IBD patients suffer from antioxidant defenses weakening, through, for instance, an impaired activity of superoxide dismutases (SOD)-that catalyze the dismutation of superoxide-or other endogenous antioxidant enzymes including catalase and glutathione peroxidase. Manganese complexes mimicking SOD activity have shown beneficial effects on cells and murine models of IBD. However, efficient SOD mimics are often manganese complexes that can suffer from decoordination and thus inactivation in acidic stomachal pH. To improve their delivery in the gut after oral administration, two SOD mimics and were loaded into lactic acid bacteria that serve as delivery vectors. When orally administrated to mice suffering from a colitis, these chemically modified bacteria (CMB) showed protective effects on the global health status of mice. In addition, they have shown beneficial effects on lipocalin-2 content and intestinal permeability. Interestingly, mRNA SOD2 content in colon homogenates was significantly decreased upon mice feeding with CMB loaded with , suggesting that the beneficial effects observed may be due to the release of the SOD mimic in the gut that complement for this enzyme. These CMB represent new efficient chemically modified antioxidant probiotics for IBD treatment.
