Controlled colonization of the human gut with a genetically engineered microbial therapeutic

by replacing native essential gene regulation with a porphyran-inducible promoter to allow reversible engraftment. Engineering a five-gene oxalate degradation pathway into the reversibly engrafting strain resulted in a therapeutic candidate that reduced hyperoxaluria, a cause of kidney stones, in preclinical models. Our phase 1/2a clinical trial demonstrated porphyran dose-dependent abundance and reversible engraftment in humans, reduction of oxalate in the urine, and characterized genetic stability challenges to achievinglong-term treatment.