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A role for bacterial urease in gut dysbiosis and Crohn's disease.
Science Translational Medicine ( IF 15.8 ) Pub Date : 2017-11-15 , DOI: 10.1126/scitranslmed.aah6888
Josephine Ni 1 , Ting-Chin David Shen 1 , Eric Z Chen 2 , Kyle Bittinger 3 , Aubrey Bailey 4 , Manuela Roggiani 5 , Alexandra Sirota-Madi 6 , Elliot S Friedman 1 , Lillian Chau 1 , Andrew Lin 1 , Ilana Nissim 7 , Justin Scott 6 , Abigail Lauder 4 , Christopher Hoffmann 4 , Gloriany Rivas 8 , Lindsey Albenberg 9 , Robert N Baldassano 9 , Jonathan Braun 10 , Ramnik J Xavier 6, 10, 11 , Clary B Clish 6 , Marc Yudkoff 7 , Hongzhe Li 2 , Mark Goulian 5 , Frederic D Bushman 4 , James D Lewis 1, 2 , Gary D Wu 1
Affiliation  

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 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 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.

中文翻译:

细菌脲酶在肠道菌群失调和克罗恩病中的作用。

炎症性肠病期间的肠道菌群失调涉及与宿主肠道炎症相关的肠道微生物群的改变。我们结合鸟枪法宏基因组测序和代谢组学来分析克罗恩病儿科患者的粪便样本,发现疾病严重程度、肠道菌群失调和细菌产生游离氨基酸之间存在关联。在小鼠中使用 15N 进行的氮通量研究表明,细菌脲酶(一种通过水解宿主尿素释放氨的酶)的活性导致小鼠宿主来源的氮转移到肠道微生物群,用于氨基酸合成。将经抗生素和聚乙二醇预处理的传统鼠类宿主与表达尿素酶的共生大肠杆菌接种,会导致肠道微生物群失调,从而导致变形菌占主导地位。这与这些动物中免疫介导的结肠炎的恶化有关。脲酶表达和氮通量改变在肠道菌群失调发展中的潜在作用表明,细菌脲酶可能是炎症性肠病的潜在治疗靶点。
更新日期:2017-11-16
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