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In the intestine, bacterial urease converts host-derived urea to ammonia and carbon dioxide, contributing to hyperammonemia-associated neurotoxicity and encephalopathy in patients with liver disease.
Dr. Wu et al engineered gut microbiota to reduce urease activity.
Animals were depleted of their preexisting gut microbiota and then inoculated with Altered Schaedler Flora (ASF), a defined consortium of 8 bacteria with minimal urease gene content. This resulted in establishment of a persistent new community that promoted a long-term reduction in fecal urease activity and ammonia production.
In a murine model of hepatic injury, ASF transplantation was associated with decreased morbidity and mortality demonstrating that inoculation of a prepared host with a defined gut microbiota can lead to durable metabolic changes with therapeutic utility.