Host defense peptides as a new drug lead to a strategy for inflammatory bowel disease

Drug Discov Today. 2025 Dec;30(12):104535. doi: 10.1016/j.drudis.2025.104535. Epub 2025 Nov 13.

Abstract

Inflammatory bowel diseases (IBDs) are chronic disorders affecting the gastrointestinal tract, causing severe inflammation and tissue damage. Current treatments often have adverse effects, underscoring the need for alternatives. This article is a short review of host defense peptides (HDPs), which have emerged as promising candidates for IBDs because of their antimicrobial and immunomodulatory properties. The HDPs cited include cathelicidins [e.g. LL-37-Tα1, lipid transfer protein (LTP), C-L, KR-12], defensins [e.g. human alpha defensin 5 (HD-5), human beta-defensin 2 (hBD2)], cecropins (e.g. CC34), microcins [e.g. microcin J25 (MccJ25)], brevinins (e.g. chensinin-1), proline-rich antimicrobial peptides (PrAMPs) (e.g. abaecin), type V peptides [e.g. vasopressin-neurophysin (VP-NP)], and alpha-melanocyte-stimulating hormone (α-MSH) (e.g. KPV). HDPs have immunoregulatory mechanisms, downregulating the nuclear factor kappa B (NF-κB) pathway, modulating cytokine release, and restoring homeostasis. The data suggest that HDPs have therapeutic potential for IBDs, offering a way to reduce side effects, and we focus on this issue here.

Keywords: Crohn’s disease; host defense peptides; ulcerative colitis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antimicrobial Peptides* / pharmacology
  • Antimicrobial Peptides* / therapeutic use
  • Humans
  • Inflammatory Bowel Diseases* / drug therapy
  • Inflammatory Bowel Diseases* / immunology

Substances

  • Antimicrobial Peptides