Turning Gut Bacteria into Living Antibiotic Factories That Make Antimicrobial Peptides

Narrative review surveying published research on engineered probiotic bacteria that produce antimicrobial peptides, including genetic engineering strategies, oral delivery methods, gut colonization enhancement, and therapeutic applications.

Antibiotic resistance is one of the most pressing public health crises, and drug-resistant gut infections are particularly dangerous. Antimicrobial peptides are promising alternatives, but delivering them orally is normally impossible because stomach acid and digestive enzymes destroy them. Engineering probiotic bacteria to produce AMPs in the gut bypasses this problem entirely — the bacteria survive digestion and continuously produce fresh peptides at the infection site.

This review sits at the convergence of three major trends in medicine: the antimicrobial resistance crisis, the microbiome revolution, and synthetic biology. Engineering probiotic bacteria as living drug delivery vehicles could transform how we treat gut infections and manage the microbiome. The approach could eventually extend beyond AMPs to deliver other therapeutic peptides and proteins directly in the gastrointestinal tract.

As a review, this paper synthesizes existing research without presenting new data. The abstract doesn't detail systematic search criteria or evidence grading. Most AMP-producing probiotic work remains preclinical, so the review primarily covers animal studies and in vitro proof-of-concept work rather than clinical applications.