A role for bacterial urease in gut dysbiosis and Crohn's disease

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, Christian Hoffmann, Gloriany Rivas, Lindsey Albenberg, Robert N. Baldassano, Jonathan Braun, Ramnik J. Xavier, Clary B. ClishMarc Yudkoff, Hongzhe Li, Mark Goulian, Frederic D. Bushman, James D. Lewis, Gary D. Wu

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

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 andmetabolomics 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 15N 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 gutmicrobiota where it was used for amino acid synthesis. Inoculation of a conventionalmurine 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.

Original languageEnglish (US)
Article numbereaah6888
JournalScience translational medicine
Volume9
Issue number416
DOIs
StatePublished - Nov 15 2017
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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