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Engineering the gut microbiota to treat hyperammonemia.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2015 Jul 01; Vol. 125 (7), pp. 2841-50. Date of Electronic Publication: 2015 Jun 22. - Publication 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.
- Subjects :
- Ammonia metabolism
Animals
Bacteria enzymology
Bacteria genetics
Bacterial Proteins genetics
Bacterial Proteins metabolism
Bioengineering
Chemical and Drug Induced Liver Injury therapy
Digestive System metabolism
Disease Models, Animal
Feces microbiology
Female
Genes, Bacterial
Hyperammonemia metabolism
Male
Mice
Mice, Inbred C57BL
Mice, SCID
Time Factors
Urease genetics
Urease metabolism
Biological Therapy methods
Digestive System microbiology
Hyperammonemia microbiology
Hyperammonemia therapy
Microbiota physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1558-8238
- Volume :
- 125
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 26098218
- Full Text :
- https://doi.org/10.1172/JCI79214