Engineering the gut microbiota to treat hyperammonemia.
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 am...
| Publicado en: | Journal of Clinical Investigation Vol. 125; no. 7; pp. 2841 - 2851 |
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| Autores principales: | , , , , , , , , , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
American Society for Clinical Investigation
Jul2015
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=109592605&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 109592605 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00219738 0YX jtl: Journal of Clinical Investigation issn: 00219738 maglogo: N pubinfo: dt: Jul2015 vid: 125 iid: 7 pid: 11983 pub: American Society for Clinical Investigation place: Ann Arbor, Michigan artinfo: ui: 109592605 NLM26098218 2013088679 10.1172/JCI79214 NLM26098218 PMC4563680 109592605 ppf: 2841 ppct: 10 formats: tig: atl: Engineering the gut microbiota to treat hyperammonemia. aug: au: Shen, Ting-Chin David Albenberg, Lindsey Bittinger, Kyle Chehoud, Christel 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 Yudkoff, Marc Bushman, Frederic D Wu, Gary D sug: subj: Microbiota ab: 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. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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