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Engineering the Gut Microbiota to Treat Hyperammonemia



Introduction of microbial compositions with minimal activity of ammonia production can alter the microbial community in the gut and reduce overall ammonia production.




Increasing evidence indicates (i) that the gut microbiota can be altered to ameliorate or prevent disease states, and (ii) that engineering the gut microbiota to therapeutically modulate host metabolism is an emerging goal of microbiome research.


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.




Potential treatment of gut dysbiosis in liver diseases, congenital hyperammonemia or Crohn’s disease.




•       Therapy for metabolic diseases that lead to hyperammonemia.




•       Altered microbial composition in gut and reduced level of ammonia in vivo.

•       Unlike treatment with antibiotics, no development of antibiotic resistance


Stage of Development


Preclinical Discovery


Intellectual Property


1.       Issued Patent(s): 10,058,576

2.       Application Pending in the US, EU, AU, CA



Reference Media


Ni et al. Sci Transl Med, 2017, 9 – 416.

Shen et al. PLoS One, 2016, 11 – 5.

Shen et al. J Clin Invest, 2015, 125 – 2841.


Desired Partnerships


1.       License

2.       Co-development


Docket #: 14-6818



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Patent Information:
For Information, Contact:
Viviane Martin
Director, PSOM Licensing Group
University of Pennsylvania
Gary Wu
Frederic Bushman
James Lewis