Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Sci Transl Med. 2017 Nov 15;9(416). 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 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 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 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.
肠道菌群失调与炎症性肠病有关，涉及与宿主肠道炎症相关的肠道微生物群的改变。我们使用组合的鸟枪法宏基因组测序和代谢组学分析了来自患有克罗恩病的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。使用 N 在小鼠中进行的氮通量研究表明，细菌脲酶的活性通过宿主尿素的水解释放氨，导致来自小鼠宿主的氮转移到肠道微生物群中，在那里用于氨基酸合成。用工程化表达脲酶的共生体接种经抗生素和聚乙二醇预处理的常规小鼠宿主会导致肠道微生物群失调，导致变形菌门物种的优势。这与这些动物中免疫介导的结肠炎恶化有关。改变的脲酶表达和氮通量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。
