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

作者：Ni Josephine; Shen Ting Chin David; Chen Eric Z; Bittinger Kyle; Bailey Aubrey; Roggiani Manuela; Sirota Madi Alexandra; Friedman Elliot S; Lin Lillian Chau Andrew; Nissim Ilana; Scott Justin; Lauder Abigail; Hoffmann Christian; Rivas Gloriany; Albenberg Lindsey; Baldassano Robert N; Braun Jonathan; Xavier Ramnik J; Clish Clary B; Yudkoff Marc; Li Hongzhe; Goulian Mark; Bushman Frederic D; Lewis James D; Wu Gary D^*

来源：Science Translational Medicine, 2017, 9(416): eaah6888.

DOI：10.1126/scitranslmed.aah6888

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 N-15 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.

• 出版日期2017-11-15