Putative role of helminths in mucosal regeneration for tissue engineering of gastrointestinal tract: A hypothesis

Helminths are increasingly recognized as important modifiers of gastrointestinal (GI) homeostasis, while anthelmintic resistance is a growing challenge in veterinary and human medicine.GI tissue engineering has advanced rapidly through organoid-based constructs, cell sheets, and biomaterial scaffolds designed to restore damaged intestinal tissue.Clinical translation, however, occurs in a lumen densely populated by microbiota and, in some hosts, helminths, creating a complex biotic environment that may influence graft integration, infection risk, mucosal healing, and stem cell behavior.While bacterial and viral effects on GI regeneration are well studied, the role of helminths remains largely overlooked.This review focuses on two central themes: How GI helminths may shape regenerative responses, and how anthelmintic resistance affects the safety and feasibility of tissue-engineering strategies.We discuss how helminths may alter immune tone, epithelial renewal, and microbial composition; how resistant helminths may complicate pre-operative infection control; and how these factors intersect with antimicrobial resistance and microbiota-dependent regulation of intestinal stem cells.We also consider whether helminth-derived molecules could serve as controlled pro-regenerative tools, while noting that most translational applications remain preliminary.Rather than presenting the helminth-microbiota-tissue regeneration triad as an established model, we frame it as a conceptual hypothesis for organizing current evidence and identifying key research gaps.