Advanced microbiome therapeutics as a novel modality for oral delivery of peptides to manage metabolic diseases.

The rising prevalence of metabolic diseases calls for innovative treatments. Peptide-based drugs have transformed the management of conditions such as obesity and type 2 diabetes. Yet, challenges persist in oral delivery of these peptides. This review explores the potential of 'advanced microbiome therapeutics' (AMTs), which involve engineered microbes for delivery of peptides in situ, thereby enhancing their bioavailability. Preclinical work on AMTs has shown promise in treating animal models of metabolic diseases, including obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease. Outstanding challenges toward realizing the potential of AMTs involve improving peptide expression, ensuring predictable colonization control, enhancing stability, and managing safety and biocontainment concerns. Still, AMTs have potential for revolutionizing the treatment of metabolic diseases, potentially offering dynamic and personalized novel therapeutic approaches.