Engineering the gut microbiota to treat hyperammonemia

Posted by & filed under Part 08: AMINO ACIDS.

Gut microbiota can be altered to ameliorate or prevent disease states. 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.

In their JCI paper, Shen and colleagues engineered murine 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 protocol resulted in establishment of a persistent new community that promoted a long-term reduction in fecal urease activity and ammonia production. Moreover, in a murine model of hepatic injury, ASF transplantation was associated with decreased morbidity and mortality. These results provide proof of concept that inoculation of a prepared host with a defined gut microbiota can lead to durable metabolic changes with therapeutic utility. Besides liver diseases, urea cycle disorders are also targets for this therapeutic approach.

http://www.jci.org/articles/view/79214

Posted by Nicola Brunetti-Pierri

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