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Karunadasa H, Vasudevan A. Therapeutic peptides in inflammatory bowel disease: From mechanistic rationale to clinical translation. World J Transl Med 2026; 12(4): 124866 [DOI: 10.5528/wjtm.124866]
World J Transl Med. Nov 28, 2026; 12(4): 124866 Published online Nov 28, 2026. doi: 10.5528/wjtm.124866
Therapeutic peptides in inflammatory bowel disease: From mechanistic rationale to clinical translation
Hirannya Karunadasa, Abhinav Vasudevan
Hirannya Karunadasa, Abhinav Vasudevan, Department of Gastroenterology, Eastern Health, Box Hill 3128, Victoria, Australia
Abhinav Vasudevan, Eastern Clinical School, Monash University, Box Hill 3128, Victoria, Australia
Author contributions: Karunadasa H writing-original draft, review & editing; Vasudevan A conceptualisation, writing-review & editing, supervision.
AI contribution statement: AI tools were not used in the preparation of this manuscript.
Conflict-of-interest statement: Vasudevan A has received speaker consultation fees from Abbvie, Ferring and Pfizer. Karunadasa H has no declarations.
Corresponding author: Abhinav Vasudevan, PhD, Adjunct Associate Professor, FRACP, Department of Gastroenterology, Eastern Health, No. 8 Arnold Street, Box Hill 3128, Victoria, Australia. abhinav.vasudevan@monash.edu
Received: June 25, 2026 Revised: August 11, 2026 Accepted: October 8, 2026 Published online: November 28, 2026 Processing time: 132 Days and 5.8 Hours
Abstract
Although therapeutic advancements have transformed treatment of inflammatory bowel disease (IBD), many patients fail to achieve a durable corticosteroid-free remission, highlighting an apparent therapeutic ceiling. This has prompted interest in novel treatment strategies that target pathways not yet fully addressed by existing therapies. Therapeutic peptides represent an emerging and mechanistically diverse class of agents with potential applications in IBD. Occupying an intermediate space between small molecules and biologics, peptides offer theoretical advantages including high target specificity, structural adaptability, capacity to modulate protein-protein interactions and relatively predictable metabolism. This narrative review summarises the rationale for the development of therapeutic peptides in IBD and evaluates key candidates across major mechanistic classes including anti-inflammatory, antimicrobial and barrier supportive peptides. Although preclinical findings and early clinical data are encouraging, substantial barriers to translation remain, including limited stability and bioavailability, delivery challenges, manufacturing complexity, incomplete long-term safety and efficacy data and regulatory considerations. Well-designed clinical trials are therefore required to establish efficacy, safety and optimal positioning of peptide-based therapies within existing treatment paradigms. Therapeutic peptides are unlikely to replace established therapies in the near term but may ultimately complement current IBD management by targeting additional disease pathways and expanding the therapeutic armamentarium.
Core Tip: Therapeutic peptides represent a promising but still largely unproven class of agents in inflammatory bowel disease (IBD). Therapeutic peptides offer potential advantages over small molecules and biologic therapies and may provide clinicians with novel therapeutic options for IBD. This review highlights the rationale for peptide-based therapies in IBD, summarises key candidates across major classes of peptides and potential barriers to widespread use in IBD.
