NDLI: Engineering the gut microbiota to treat hyperammonemia.

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Engineering the gut microbiota to treat hyperammonemia.

Content Provider	Semantic Scholar
Author	Shen, Ting-Chin David Albenberg, Lindsey Bittinger, Kyle Chehoud, Christel Sjoland Chen, Ying-yu Judge, Colleen A. Chau, Lillian Ni, Josephine Sheng, Michael Lin, Andrew Wilkins, Benjamin J. Buza, Elizabeth L. Lewis, James D. Daikhin, Yevgeny Nissim, Ilana B. Yudkoff, Mark Bushman, Frederic D. Wu, Gary D.
Copyright Year	2015
Abstract	Increasing evidence indicates that the gut microbiota can be altered to ameliorate or prevent disease states, and 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. Here, we 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.
Starting Page	790
Ending Page	793
Page Count	4
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.jci.org/articles/view/79214/version/2/pdf/render
Alternate Webpage(s)	https://www.jci.org/articles/view/79214/version/1/pdf/render
PubMed reference number	26098218v1
Alternate Webpage(s)	https://doi.org/10.1172/JCI79214
DOI	10.1172/JCI79214
Journal	The Journal of clinical investigation
Volume Number	125
Issue Number	7
Language	English
Access Restriction	Open
Subject Keyword	Ammonia measurement Brain Diseases Carbon Dioxide Chemical and Drug Induced Liver Injury Contribution Fecal occult blood test Gastrointestinal Microbiome Hyperammonemia Intestinal Microbiome Intestinal Wall Tissue Intestines Liver diseases Microbiota (plant) Morbidity - disease rate Neurotoxicity Syndromes Patients Urea Urease negative regulation of gut granule assembly
Content Type	Text
Resource Type	Article

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