Oral delivery of a Lactococcus lactis strain secreting bovine lactoferricin-lactoferrampin alleviates the development of acute colitis in mice

摘要

Ulcerative colitis (UC) is a chronic relapsing disease. Treatment of UC would benefit from specific targeting of therapeutics to the intestine. Previous studies have demonstrated that bovine lactoferricin and lactoferrampin have bactericidal, anti-inflammatory, and immunomodulatory effects. Here, we investigated whether oral administration of a bovine lactoferricin-lactoferrampin (LFCA)-encoding Lactococcus lactis (LL-LFCA) strain could alleviate experimental colitis. LFCA derived from LL-LFCA inhibited the growth of Escherichia coli and Staphylococcus aureus in vitro. In mice, administration of LL-LFCA decreased the disease activity index and attenuated dextran sulfate sodium (DSS)-induced body weight loss and colon shortening. LL-LFCA treatment also ameliorated DSS-induced colon damage, inhibited inflammatory cell infiltration, significantly decreased myeloperoxidase activity, and ameliorated DSS-induced disruption of intestinal permeability and tight junctions. In addition, 16S rDNA sequencing showed that LL-LFCA reversed DSS-induced gut dysbiosis. The production of proinflammatory mediators in serum and the colon was also reduced by administration of LL-LFCA. In vitro, LFCA derived from LL-LFCA decreased the messenger RNA expression of proinflammatory factors. The underlying mechanisms may involve inhibition of the nuclear factor kappa B (NF-kappa B) pathway. The results demonstrate that LL-LFCA ameliorates DSS-induced intestinal injury in mice, suggesting that LL-LFCA might be an effective drug for the treatment of inflammatory bowel diseases.