Bifidobacterium longum as an Orally Administered Carrier of Human-Beta-Defensin-2 to Treat Colonic Crohn’s Disease

Abstract

Crohn's disease (CD) is a chronic, long-term condition that causes chronic inflammation in the digestive tract, and shows an increasing incidence and prevalence worldwide. Defensins deficiency causes the defect of endogenous antibiotics to reduce the bactericidal activity of the organism, and leads to the occurrence of CD. Human beta-defensin-2 (HBD-2) is antimicrobial peptide discovered in lesional skin, which is is inadequate in colonic CD. In the present study, we engineered bifidobacterium longum (B. longum) as an expression system of bioactive HBD-2, and used its oral delivery to treat colonic CD mice induced through TNBS. The data showed that engineered B. longum successfully secreted HBD-2 with antibacterial property, and it also has effective antiendotoxin and antioxidant activities in LPS-induced Caco-2 cells. In the CD murine model experiment, results based on the the levels of immunity correlating cytokines IL-4, IL-10, TNF-?, TGF-?, and IFN-?, and transcription factor T-bet, GATA-3, and Foxp3, as well as the histological injury of colon tissue, revealed B. longum-HBD-2 was efficient in attenuating TNBS-induced CD. The results demonstrate that is a feasible pharmaceutical for fighting colonic Crohn’s disease.