Abstract

Summary Reactive oxygen species (ROS)-induced gut microbiota dysbiosis is a pivotal driver of intestinal inflammation. Clinical data mining reveals that patients with inflammatory bowel disease (IBD) exhibit elevated oxidative stress and decreased SOD2 expression, both correlating strongly with inflammatory onset. Based on these findings, we engineered an oral probiotic strain, KI@lSodA, derived from Lactococcus lactis NZ9000, to constitutively express its superoxide dismutase (SodA) for the treatment of intestinal inflammation. In murine models of DSS-induced enteritis, oral administration of KI@lSodA significantly attenuated intestinal inflammation and repaired epithelial barrier damage under both acute and chronic conditions. Mechanistically, the engineered Lactococcus restored gut microbial homeostasis by increasing beneficial commensal bacteria and suppressing the infiltration of phagocytes, including neutrophils and macrophages. By modulating the innate and adaptive immune landscapes, this approach offers a potential strategy for treating IBD and preventing disease progression through the targeted restoration of redox balance and gut microbiota health.