Emerging antimicrobial peptides in gastrointestinal disorders: Dual role in immunity and therapy

Table 1 Key antimicrobial peptides: Structural classes, mechanisms, molecular targets, and gastrointestinal relevance

AMP	Structural class	Primary mechanism(s)	Molecular target(s)	GI relevance	Ref.
HD-5, HD-6	α-Defensin	Membrane disruption; microbiome shaping via crypt gradients	Lipid II (HD-5); self-assembly nets (HD-6)	Paneth cell-derived; reduced in ileal Crohn’s disease	[4,14]
hBD-2	β-Defensin (inducible)	Membrane disruption; CCR6-mediated chemotaxis	Lipid II; CCR6	NF-κB-induced in IBD epithelium; inducible barrier	[4,5]
LL-37	Cathelicidin (α-helix)	Membrane disruption; DNA binding; receptor-mediated signalling	FPR2/ALX (approximately 200 nM), EGFR, TLR9 via DNA	Wound healing; context-dependent pro-/anti-tumour in CRC	[17,21]
Buforin II	α-Helix (proline hinge)	Non-lytic entry; DNA/RNA binding	dsDNA minor groove; rRNA	Model for resistance-refractory intracellular targeting	[5,9]
Nisin	Lantibiotic (cyclic)	Lipid II sequestration and pore formation	Lipid II pyrophosphate (approximately 1 nM)	Narrow-spectrum; resistance-resistant dual-mechanism paradigm	[2,20]
Microcin J25	Lasso peptide	RNA polymerase inhibition; membrane-independent	RNA polymerase β-subunit	Efficacious in DSS-induced colitis; selective microbiome modulator	[22]
CRAMP	Cathelicidin (α-helix)	Membrane disruption; FPR2/ALX immunomodulation	Microbial membranes; FPR2/ALX	Anti-inflammatory in murine colitis; restores diversity	[23]

AMP: Antimicrobial peptide; CCR6: C-C chemokine receptor type 6; CRAMP: Cathelicidin-related antimicrobial peptide; CRC: Colorectal cancer; DSS: Dextran sodium sulfate; dsDNA: Double-stranded DNA; EGFR: Epidermal growth factor receptor; FPR2/ALX: Formyl peptide receptor 2/Lipoxin A4 receptor; GI: Gastrointestinal; IBD: Inflammatory bowel disease; NF-κB: Nuclear factor kappa B; RNA: Ribonucleic acid; rRNA: Ribosomal RNA; TLR9: Toll-like receptor 9.