LL-37 · research summary

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

World journal of gastrointestinal pharmacology and therapeutics · 2026. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

Review article
“This review frames AMP biology around a central duality: The same peptides that defend the gut can, when dysregulated in concentration, location, or context, contribute to pathology”

Subjects

Antimicrobial peptides (AMPs) in gastrointestinal homeostasis and disease
“Antimicrobial peptides (AMPs) are small, cationic effectors of innate immunity that are central to gastrointestinal homeostasis and increasingly attractive as therapeutics for infection, inflammation, and malignancy.”

Reported findings

AMPs exhibit a functional duality where they defend the gut but can contribute to pathology when dysregulated.
“The same peptides that defend the gut can, when dysregulated in concentration, location, or context, contribute to pathology, from the α-defensin deficiency that initiates ileal Crohn’s disease to the concentration-dependent switch by which LL-37 turns from a wound-healing mediator into a tumour-promoting one.”
Microbiological success in preclinical or clinical settings does not guarantee clinical benefit.
“We examine the mechanistic basis of AMP action (membrane disruption, intracellular targeting, and receptor-mediated immunomodulation) and evaluate preclinical and clinical evidence across inflammatory bowel disease, enteric infection, and gastrointestinal cancers, drawing the recurring lesson that microbiological success rarely guarantees clinical benefit.”
Persistent barriers to AMP therapeutics include proteolytic instability, narrow therapeutic windows, and manufacturing costs.
“Persistent barriers of proteolytic instability, narrow therapeutic windows, and manufacturing cost are increasingly addressed through convergent advances in artificial intelligence–guided peptide design, sequence stabilisation, gut-targeted and stimulus-responsive delivery, and engineered live biotherapeutics that produce peptides in situ.”

Limitations stated by the authors

The clinical evidence base for AMPs in gastrointestinal disease remains essentially preclinical, with no AMP having reached controlled clinical trials for a primary gastrointestinal indication.
“Because no AMP has yet reached controlled clinical trials for a primary gastrointestinal indication, the translational lessons drawn here are necessarily extrapolated from AMP trials in other accessible mucosal and cutaneous compartments—nasal, dermatological, oropharyngeal, and anogenital—rather than from GI-specific clinical data.”

Source: PubMed 42707805 · DOI 10.4292/wjgpt.122448 · all study summaries

Reported findings

AMPs exhibit a functional duality where they defend the gut but can contribute to pathology when dysregulated.

“The same peptides that defend the gut can, when dysregulated in concentration, location, or context, contribute to pathology, from the α-defensin deficiency that initiates ileal Crohn’s disease to the concentration-dependent switch by which LL-37 turns from a wound-healing mediator into a tumour-promoting one.”

Microbiological success in preclinical or clinical settings does not guarantee clinical benefit.

“We examine the mechanistic basis of AMP action (membrane disruption, intracellular targeting, and receptor-mediated immunomodulation) and evaluate preclinical and clinical evidence across inflammatory bowel disease, enteric infection, and gastrointestinal cancers, drawing the recurring lesson that microbiological success rarely guarantees clinical benefit.”

Persistent barriers to AMP therapeutics include proteolytic instability, narrow therapeutic windows, and manufacturing costs.

“Persistent barriers of proteolytic instability, narrow therapeutic windows, and manufacturing cost are increasingly addressed through convergent advances in artificial intelligence–guided peptide design, sequence stabilisation, gut-targeted and stimulus-responsive delivery, and engineered live biotherapeutics that produce peptides in situ.”

Limitations stated by the authors

The clinical evidence base for AMPs in gastrointestinal disease remains essentially preclinical, with no AMP having reached controlled clinical trials for a primary gastrointestinal indication.

“Because no AMP has yet reached controlled clinical trials for a primary gastrointestinal indication, the translational lessons drawn here are necessarily extrapolated from AMP trials in other accessible mucosal and cutaneous compartments—nasal, dermatological, oropharyngeal, and anogenital—rather than from GI-specific clinical data.”