Protective effects of cathelicidin-encoding Lactococcus lactis in murine ulcerative colitis.

BACKGROUND AND AIM: Intrarectal administration of mouse cathelin-related antimicrobial peptide (mCRAMP) reduced intestinal inflammation in mice. In the current study, we examined whether mCRAMP-transformed Lactococcus lactis given orally attained similar protective effects. METHOD: mCRAMP was produced and secreted from the transformed L. lactis. Murine colitis was induced by ingestion of 3% dextran sulfate sodium (DSS) for 7 days. Eight or 10 log colony forming unit (cfu) L. lactis or the transformed strains with or without nisin induction were given orally as a parallel treatment with DSS. The body weight, fecal microbiota populations, clinical symptoms and histological examinations of colonic tissues were determined. Myeloperoxidase (MPO) activity and malondialdehyde (MDA) level were also evaluated to reflect the degree of inflammation. A prototype anti-inflammatory drug sulfasalazine was used as a reference drug to compare the efficacy and mechanisms of action for ulcerative colitis (UC). RESULT: Compared with the control group with colitis, cathelicidin-transformed L. lactis could improve the clinical symptoms, maintain crypt integrity and preserve mucus content (P < 0.01). The number of apoptotic cells, MPO activity and MDA level were also significantly reduced (P < 0.05). The increases of fecal microbiota in colitis animals were markedly prevented (P < 0.001). Unlike mCRAMP-encoding L. lactis, effective doses of sulfasalazine only alleviated the clinical symptoms (P < 0.01) but not the mucosal damage in the colon. CONCLUSION: mCRAMP-transformed L. lactis has been shown to produce mCRAMP, effectively preventing murine UC. Oral administration of this biological preparation is better than sulfasalazine for the treatment of UC.