Wolff Nora S, Jacobs Max C, Haak Bastiaan W, Roelofs Joris J T H, de Vos Alex F, Hugenholtz Floor, Wiersinga W Joost
Center for Experimental and Molecular Medicine, Amsterdam Infection & Immunity Institute, Amsterdam UMC, location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands.
Department of Pathology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands.
Intensive Care Med Exp. 2020 Aug 25;8(1):47. doi: 10.1186/s40635-020-00336-w.
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.
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 CFU, intranasal).
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.
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.
微生物群已成为影响危重症患者的一系列疾病病理生理学中的重要因素。我们推测，不同供应商提供的小鼠微生物群组成差异可能会影响肺部脂多糖（LPS）炎症和革兰氏阴性菌肺炎的小鼠模型。
采用多供应商方法，使用来自三个不同供应商（扬维耶、Envigo、查尔斯河）的基因相似小鼠。该模型用于研究对宿主对肺部LPS刺激（1μg肺炎克雷伯菌LPS，鼻内给药）以及实验性肺炎克雷伯菌感染（ATCC43816，1×10CFU，鼻内给药）的反应的影响。
肠道微生物群分析显示，细菌组成在不同供应商之间存在显著差异，这在β多样性和不同分类水平上均有体现。在用LPS鼻内治疗6小时和24小时后，测定肺和支气管肺泡灌洗液（BALF）中肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6的释放。除Envigo外，各实验组之间未发现差异，Envigo组在6小时时肺和BALF中的TNFα水平高于扬维耶和查尔斯河组。在另一组实验中，对来自不同供应商的小鼠进行了革兰氏阴性菌肺炎（肺炎克雷伯菌）的临床相关模型实验。在感染后12小时和36小时，未发现不同供应商之间在细菌播散、肺中TNFα和IL-6水平方面存在差异。同样，各实验组之间器官衰竭标志物也无差异。
尽管不同供应商提供的小鼠肠道微生物群组成存在显著差异，但对我们的肺部炎症和重症肺炎模型的假设影响有限。这对实验设置具有重要意义，表明肠道微生物群的差异不一定会导致结果的差异。
