Title |
A role for bacterial urease in gut dysbiosis and Crohn’s disease
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Published in |
Science Translational Medicine, November 2017
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DOI | 10.1126/scitranslmed.aah6888 |
Pubmed ID | |
Authors |
Josephine Ni, Ting-Chin David Shen, Eric Z Chen, Kyle Bittinger, Aubrey Bailey, Manuela Roggiani, Alexandra Sirota-Madi, Elliot S Friedman, Lillian Chau, Andrew Lin, Ilana Nissim, Justin Scott, Abigail Lauder, Christopher Hoffmann, Gloriany Rivas, Lindsey Albenberg, Robert N Baldassano, Jonathan Braun, Ramnik J Xavier, Clary B Clish, Marc Yudkoff, Hongzhe Li, Mark Goulian, Frederic D Bushman, James D Lewis, Gary D Wu |
Abstract |
Gut dysbiosis during inflammatory bowel disease involves alterations in the gut microbiota associated with inflammation of the host gut. We used a combination of shotgun metagenomic sequencing and metabolomics to analyze fecal samples from pediatric patients with Crohn's disease and found an association between disease severity, gut dysbiosis, and bacterial production of free amino acids. Nitrogen flux studies using (15)N in mice showed that activity of bacterial urease, an enzyme that releases ammonia by hydrolysis of host urea, led to the transfer of murine host-derived nitrogen to the gut microbiota where it was used for amino acid synthesis. Inoculation of a conventional murine host (pretreated with antibiotics and polyethylene glycol) with commensal Escherichia coli engineered to express urease led to dysbiosis of the gut microbiota, resulting in a predominance of Proteobacteria species. This was associated with a worsening of immune-mediated colitis in these animals. A potential role for altered urease expression and nitrogen flux in the development of gut dysbiosis suggests that bacterial urease may be a potential therapeutic target for inflammatory bowel diseases. |
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Demographic breakdown
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Scientists | 21 | 33% |
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Science communicators (journalists, bloggers, editors) | 2 | 3% |
Mendeley readers
Geographical breakdown
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Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 41 | 14% |
Student > Master | 31 | 11% |
Student > Bachelor | 21 | 7% |
Other | 18 | 6% |
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Unknown | 74 | 26% |
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Chemistry | 10 | 3% |
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Unknown | 88 | 30% |