Advanced microbiome therapeutics for oral delivery of peptides and proteins: Advances, challenges, and opportunities

Peptide and protein medicines have changed the therapeutic landscape for many diseases, yet oral delivery remains a significant challenge due to enzymatic degradation, instability, and poor permeability in the gastrointestinal tract. Advanced Microbiome Therapeutics (AMTs) could overcome some of these barriers by producing and releasing therapeutic peptides directly in the gastrointestinal tract. AMTs can localize peptide production at the site of absorption, providing either sustained or controlled release while potentially reducing side effects associated with systemic administration. Here, this review assesses the status of AMTs for oral peptide delivery and discusses the potential integration of permeation enhancers, mucoadhesive systems, and receptor-mediated transport strategies to improve oral bioavailability further. Combining these approaches could pave the way for more widespread oral delivery strategies for peptide and protein medicines.