Cathelicidin-encoding Lactococcus lactis promotes mucosal repair in murine experimental colitis

Area of Science:

• Gastroenterology
• Microbiology
• Molecular Biology

Background:

• Previous studies demonstrated the preventive effects of mouse cathelicidin (mCRAMP) and mCRAMP-encoding Lactococcus lactis (N4I) in experimental colitis.
• It remains crucial to ascertain N4I's capacity to facilitate mucosal healing in established colitis models.

Purpose of the Study:

• To evaluate the therapeutic potential of N4I in promoting mucosal repair in mice with existing dextran sulfate sodium-induced ulcerative colitis (UC).
• To investigate the direct mechanisms by which mCRAMP influences colonic wound healing in vitro.

Main Methods:

• Mice with UC were orally administered L. lactis (N4I) or its modified strains, with sulfasalazine as a reference drug.
• Clinical, histological, and colonic tissue parameters were assessed.
• In vitro studies utilized young adult mouse colon cells to explore mCRAMP's wound repair mechanisms via the GPCR/MAPK pathway.

Main Results:

• N4I treatment improved clinical symptoms, maintained crypt integrity, and preserved the mucus-secreting layer in colitis-affected animals.
• N4I demonstrated cell protective and proliferative effects.
• In vitro, mCRAMP accelerated cell migration, indicating direct wound repair promotion, independent of proliferation, via the GPCR/MAPK pathway.
• Sulfasalazine alleviated clinical symptoms but did not significantly improve mucosal damage or repair.

Conclusions:

• mCRAMP-encoding L. lactis (N4I) exhibits significant potential for promoting mucosal repair in ulcerative colitis.
• N4I may represent a superior therapeutic strategy compared to traditional anti-inflammatory agents for UC treatment.