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

Table 2 Preclinical studies of antimicrobial peptide activity in gastrointestinal and related disease models

No.	Ref.	Peptide	Model / route	Dose	Key findings	Sig.
1	Moghaddam et al[49]	CM11; CM15 (cecropin-melittin hybrids)	In vitro: P. aeruginosa, S. aureus, V. cholerae, A. baumannii, E. coli (ATCC and clinical)	MIC 4 mg/L; MBC 16 mg/L	Complete kill at 30-40 minutes; CM11 MIC/MBC stable at 48 hours; CM15 MIC doubled at 48 hours	P < 0.05
2	Shang et al[22]	MccJ25 (lasso peptide, 21-aa)	DSS-induced UC; C57BL/6J/oral gavage	5 mg/kg and 10 mg/kg	↓ DAI, ↑ colon length; ↓ TNF-α, IFN-γ, IL-1β, IL-6; ↑ TJ proteins; ↑ Lactobacillus, ↓ Bacteroides and Akkermansia; co-housing confirmed microbiota as key mechanism	P < 0.05
3	Jiang et al[23]	CRAMP (cathelicidin-related; murine LL-37 homologue)	3% DSS-induced acute UC; C57BL/6J/IP	4 mg/kg/day	↑ body weight, ↑ colon length, ↓ DAI, ↓ MPO; ↑ TJ proteins; ↓ IL-6, TNF-α, MCP-1, CRP; ↑ GSH-PX, ↓ MDA; ↑ Verrucomicrobiota	P < 0.05-0.001
4	Liu et al[44]	Abaecin (proline-rich, bee-derived; non-lytic)	2.5% DSS-induced acute UC; C57BL/6J/rectal	5 mg/kg	↑ colon length and body weight, ↓ DAI; ↓ LPS, D-LA, DAO; ↓ IL-1β, IL-6, TNF-α, IFN-γ (IL-10 unchanged); ↑ ZO-1, occludin, claudin-1; ↓ NF-κB/MAPK; ↓ Bacteroides, Barnesiella, Escherichia, ↑ Lactobacillus	P < 0.05-0.01
5	Sun et al[45]	Chensinin-1b (from R. chensinensis)	RAW264.7 + LPS (in vitro) and 4% DSS-induced UC; BALB/c/IP	10-40 μmol/L; 1.5 and 3 mg/kg	↓ M1 markers (TNF-α, IL-6, NO, CD86), ↑ M2 markers (IL-10, TGF-β1, Arg-1, CD206); ↓ NF-κB/MAPK; ↑ body weight and colon length, ↓ DAI; high dose superior to cyclosporine A	P < 0.05-0.01
6	Zhao et al[43]	DP7 (12-aa; machine-learning designed)	4% DSS-induced UC (multi-arm: FMT, antibiotic, pseudo-germ-free); C57BL/6/IV	0.5 mg/kg q2d	↓ weight loss, ↓ DAI, ↑ colon length; ↑ ZO-1, claudin-1, occludin; ↓ IL-1β, IL-6, ↑ IL-10; ↑ Muribaculaceae; DP7-FMT > DSS-FMT, immune effects microbiota-dependent	P < 0.05-0.0001
7	Sun et al[46]	R7I (IRPI × 7; anti-proteolytic; trypsin/chymotrypsin/pepsin-resistant)	E. coli ATCC 25922 enteritis; C57BL/6/oral gavage	20 mg/kg, 30 mg/kg, 40 mg/kg	↓ intestinal and hepatic inflammation, restored barrier; modulated microbiota (↓ Clostridia, ↑ Odoribacteraceae); normalised gut metabolites	P < 0.05

Arg-1: Arginase-1; ATCC: American Type Culture Collection; CD206: Cluster of differentiation 206; CRAMP: Cathelicidin-related antimicrobial peptide; CRP: C-reactive protein; DAI: Disease activity index; DAO: Diamine oxidase; DP7: Designed peptide 7; DSS: Dextran sodium sulfate; FMT: Faecal microbiota transplantation; GSH-PX: Glutathione peroxidase; IFN-γ: Interferon gamma; IL: Interleukin; IP: Intraperitoneal; IRPI: Isoleucine-arginine-proline-isoleucine motif; IV: Intravenous; LPS: Lipopolysaccharide; MAPK: Mitogen-activated protein kinase; MBC: Minimum bactericidal concentration; MccJ25: Microcin J25; MCP-1: Monocyte chemoattractant protein-1; MDA: Malondialdehyde; MIC: Minimum inhibitory concentration; MPO: Myeloperoxidase; NF-κB: Nuclear factor kappa B; NO: Nitric oxide; q2d: Every 2 days; R7I: Arginine-isoleucine repeat peptide (IRPI × 7); RAW264.7: Murine macrophage cell line; TGF-β1: Transforming growth factor beta 1; TJ: Tight junction; UC: Ulcerative colitis; ZO-1: Zonula occludens-1.