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. SOD mimics or mimetics (SODm) can be loaded in <i>Lactiplantibacillus plantarum</i> strains to create chemically modified bacteria (CMB) able to deliver SODm in digestive tract.Loaded bacteria (CMB) possess an increased anti-superoxide activity.Orally administrated CMB significantly decrease colitis symptoms in mice.CMB complement for the SOD2 in inflammed colonic homogenates.CMB are potential antioxidant probiotics for inflammatory bowel diseases (IBD). SOD mimics or mimetics (SODm) can be loaded in <i>Lactiplantibacillus plantarum</i> strains to create chemically modified bacteria (CMB) able to deliver SODm in digestive tract. Loaded bacteria (CMB) possess an increased anti-superoxide activity. Orally administrated CMB significantly decrease colitis symptoms in mice. CMB complement for the SOD2 in inflammed colonic homogenates. CMB are potential antioxidant probiotics for inflammatory bowel diseases (IBD).