Background The microbiome has emerged as an important player in the pathophysiology of a whole spectrum of diseases that affect the critically ill. We hypothesized that differences in microbiota composition across vendors can influence murine models of pulmonary lipopolysaccharide (LPS) inflammation and Gram-negative pneumonia. Methods A multi-vendor approach was used with genetically similar mice derived from three different vendors (Janvier, Envigo, Charles River). This model was employed to study the effect on the host response to a pulmonary LPS challenge (1 μg Klebsiella pneumoniae LPS, intranasal), as well as experimental K. pneumoniae infection (ATCC43816 , 1 × 10 4 CFU, intranasal). Results Gut microbiota analysis revealed profound intervendor differences in bacterial composition as shown by beta diversity and at various taxonomic levels. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 release in lung and bronchoalveolar lavage fluid (BALF) were determined 6 and 24 h after intranasal treatment with LPS. No differences were found between the groups, with the exception for Envigo, showing a higher level of TNFα in lung and BALF at 6 h compared to Janvier and Charles River. In another set of experiments, mice from different vendors were subjected to a clinically relevant model of Gram-negative pneumonia ( K. pneumoniae ). At 12 and 36 h post-infection, no intervendor differences were found in bacterial dissemination, or TNFα and IL-6 levels in the lungs. In line, markers for organ failure did not differ between groups. Conclusions Although there was a marked variation in the gut microbiota composition of mice from different vendors, the hypothesized impact on our models of pulmonary inflammation and severe pneumonia was limited. This is of significance for experimental settings, showing that differences in gut microbiota do not have to lead to differences in outcome.

中文翻译：

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供应商对小鼠肠道微生物群的影响及其对脂多糖诱导的肺部炎症和革兰氏阴性肺炎的影响

背景微生物组已成为影响危重病人的一系列疾病的病理生理学中的重要参与者。我们假设供应商之间微生物群组成的差异会影响肺脂多糖 (LPS) 炎症和革兰氏阴性肺炎的小鼠模型。方法 对来自三个不同供应商（Janvier、Envigo、Charles River）的基因相似小鼠使用多供应商方法。该模型用于研究宿主对肺部 LPS 攻击（1 μg 肺炎克雷伯菌 LPS，鼻内）以及实验性肺炎克雷伯菌感染（ATCC43816，1 × 10 4 CFU，鼻内）反应的影响。结果肠道微生物群分析揭示了细菌组成的巨大干预差异，如β多样性和不同分类水平所示。在用 LPS 鼻内治疗后 6 和 24 小时测定肺和支气管肺泡灌洗液 (BALF) 中的肿瘤坏死因子 (TNF)-α 和白细胞介素 (IL)-6 释放。除 Envigo 外，两组之间没有发现差异，与 Janvier 和 Charles River 相比，6 小时时肺和 BALF 中的 TNFα 水平更高。在另一组实验中，来自不同供应商的小鼠接受了革兰氏阴性肺炎（肺炎克雷伯氏菌）的临床相关模型。在感染后 12 和 36 小时，在细菌传播或肺部 TNFα 和 IL-6 水平方面没有发现干预者差异。与此一致，各组之间器官衰竭的标志物没有差异。结论 尽管来自不同供应商的小鼠肠道菌群组成存在显着差异，对我们肺部炎症和严重肺炎模型的假设影响是有限的。这对实验环境具有重要意义，表明肠道微生物群的差异不一定会导致结果的差异。