Anti-inflammatory properties of Bifidobacterium longum expressing human manganese superoxide dismutase using the TNBS-induced rats model of colitis.

The chronic enteritis disease ulcerative colitis (UC) is a formidable opponent, and its etiology remains unclear. Current studies have shown that oxidative stress is closely related to the pathogenesis of inflammatory bowel disease. Antioxidant enzymes, such as manganese superoxide dismutase (MnSOD)，have been deemed to exert an anti-inflammatory function. Normally, oral administration of MnSOD directly leads to an incapacitation because of poor penetration and stability. To address this problem, the probiotic Bifidobacterium longum (B. longum), which naturally occurs in the intestinal flora, was engineered to secrete a biologically active human MnSOD. Then this engineered bacterium was utilized against a rat model harboring UC induced through trinitrobenzene sulfonic acid. The data showed the engineered B. longum successfully secreted a penetratin-hMn-SOD fusion protein. The bioactivity assay demonstrated that this fusion protein was delivered into Caco-2 cells and significantly decreased TNF-α (P<0.01) and IL-6 (P<0.01) expression, as well as, ROS level (P<0.001) in LPS-induced Caco-2 cells. The rat UC model experiment indicated that the B. longum harboring rhMn-SOD (penetratin-hMn-SOD) successfully inhibited the release of cytokines like TNF-a, IL-6, IL-1β and IL-8, and reduce MPO activity and MDA levels. The histological analysis of the colon tissue section revealed that the engineered B. longum was efficient in attenuating UC damage. These results suggested that preventing UC by the use of B. longum harboring rhMn-SOD could be an alternative choice.