SOD mimics delivered to the gut using lactic acid bacteria mitigate the colitis symptoms in a mouse model of inflammatory bowel diseases
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 <b>Mn1</b> and <b>Mn1C</b> 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 <b>Mn1C</b>, 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.
Authors
- Émilie Mathieu (ORCID: https://orcid.org/0000-0002-9313-8679)
- Véronique Carrière (ORCID: https://orcid.org/0000-0002-6263-0847)
- Alice Balfourier (ORCID: https://orcid.org/0000-0002-4801-1388)
- Luis G. Bermúdez‐Humarán (ORCID: https://orcid.org/0000-0001-7525-3131)
- Sylvie Demignot (ORCID: https://orcid.org/0000-0001-7149-1992)
- Elodie Quévrain
- C. Carbonne
- Gabrielle Schanne (ORCID: https://orcid.org/0000-0002-8601-1485)
- Sophie Thenet (ORCID: https://orcid.org/0000-0002-0336-2942)
- Clotilde Policar (ORCID: https://orcid.org/0000-0003-0255-1650)
- Pauline Ruffié
- Amandine Vincent
- Philippe Langella (ORCID: https://orcid.org/0000-0001-5960-4341)
- Philippe Seksik (ORCID: https://orcid.org/0000-0003-3596-9893)
- Nassim Hammoudi (ORCID: https://orcid.org/0000-0001-9273-9133)
- Nicolas Delsuc (ORCID: https://orcid.org/0000-0001-5570-8311)
- Magali Svreck
Institutions
- École Nationale Supérieure de Chimie de Montpellier (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- École Pratique des Hautes Études (FR)
- Université Paris Cité (FR)
- AgroParisTech (FR)
- Université Paris Sciences et Lettres (FR)
- Université Paris-Saclay (FR)
- École Normale Supérieure - PSL (FR)
- Microbiologie de l’alimentation au service de la santé (FR)
- Sorbonne Université (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Hôpital Saint-Antoine (FR)
- Fédération Hospitalo-Universitaire, Paris Center for Microbiome Medicine (FR)
- Centre de Recherche Saint-Antoine (FR)
- Hôpital Saint-Louis (FR)
- Laboratoire des Biomolécules (FR)
Publication Details
- Journal
- Free Radical Research
- Published
- 2025-03-04
- DOI
- https://doi.org/10.1080/10715762.2025.2478121
- Citations
- 1
- Primary Topic
- Probiotics and Fermented Foods
- Type
- article
- Field-Weighted Citation Impact
- 1.16
Funders
- Centre National de la Recherche Scientifique
- AgroParisTech
- Sorbonne Université
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement