Antimicrobial peptides are endogenous peptides typically expressed on mucosal surfaces, such as the mouth, intestines, and respiratory tract. These mucosal surfaces are typically in close contact with the external environment and microbiota. Over the last decade, the role of antimicrobial peptides in colitis has become increasingly apparent, and some antimicrobial peptides show promise as future therapeutic approaches to treat colitis. Pharmaceutical companies and laboratories are developing clinically useful versions of antimicrobial peptides with high efficacy, robust chemical stability, and excellent safety profile.

Cathelicidin

Cathelicidin is a 37-amino acid antimicrobial peptide called LL-37 in humans and mCRAMP in mice. It may directly kill bacteria by pore formation on the cell membrane. Cathelicidin may bind to the bacterial sensor formyl peptide receptor-like 1 (FPRL1) and mediate its chemotactic activity in immune cells. Cathelicidin  play a role in inhibiting colitis-associated intestinal fibrosLs in Crohn’s Disease patients.

Lactoferrin

Lactoferrin is a glycoprotein originally found in milk. Deficiency of lactoferrin augments azoxymethane- and DSS-mediated colitis-associated colorectal dysplasia in mice. Oral feeding of lactoferrin specificity reduces DSS-mediated colitis in rats. Despite promising preclinical findings, lactoferrin has not been used to treat IBD patients in clinical trials.

Elafin

Elafin consists of 117 amino acids and possesses antimicrobial and anti-protease activities. Colonic Elafin mRNA expression is increased in UC patients, but not CD patients and healthy control subjects. Elafin is typically found in colonic epithelial cells of UC patients. In terms of therapeutic potential of elafin, elafin-expressing food grade lactic acid bacteria significantly inhibit DSS-mediated acute colitis and CD4CD45RBhimediated chronic colitis in mice. However, it is not known whether elafin is useful in clinical applications.

Conclusion

Antimicrobial peptides are novel and potentially useful approaches to treating various forms of colitis. One approach is to induce expression of cathelicidin by butyrate or vitamin D. Another approach may be the development antimicrobial peptide mimics. Some of the endogenous antimicrobial peptides may also serve as biomarkers for indicating disease activity of colitis.