Ellekilde M, Krych L, Hansen C H F, Hufeldt M R, Dahl K, Hansen L H, Sørensen S J, Vogensen F K, Nielsen D S, Hansen A K
Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Grønnegårdsvej 18, DK-1870 Frederiksberg C, Denmark.
Department of Food Science, Faculty of Science, University of Copenhagen, Rolighedsvej 30, DK-1958 Frederiksberg, Denmark.
Res Vet Sci. 2014 Apr;96(2):241-50. doi: 10.1016/j.rvsc.2014.01.007. Epub 2014 Feb 3.
Gut microbiota have been implicated as a relevant factor in the development of type 2 diabetes mellitus (T2DM), and its diversity might be a cause of variation in animal models of T2DM. In this study, we aimed to characterise the gut microbiota of a T2DM mouse model with a long term vision of being able to target the gut microbiota to reduce the number of animals used in experiments. Male B6.V-Lep(ob)/J mice were characterized according to a number of characteristics related to T2DM, inflammation and gut microbiota. All findings were thereafter correlated to one another in a linear regression model. The total gut microbiota profile correlated to glycated haemoglobin, and high proportions of Prevotellaceae and Lachnospiraceae correlated to impaired or improved glucose intolerance, respectively. In addition, Akkermansia muciniphila disappeared with age as glucose intolerance worsened. A high proportion of regulatory T cells correlated to the gut microbiota and improved glucose tolerance. Furthermore, high levels of IL-10, IL-12 and TNF-α correlated to impaired glucose tolerance, blood glucose or glycated haemoglobin. The findings indicate that gut microbiota may contribute to variation in various disease read-outs in the B6.V-Lep(ob)/J model and considering them in both quality assurance and data evaluation for the B6.V-Lep(ob)/J model may have a reducing impact on the inter-individual variation.
肠道微生物群被认为是2型糖尿病（T2DM）发病的一个相关因素，其多样性可能是T2DM动物模型变异的一个原因。在本研究中，我们旨在对一个T2DM小鼠模型的肠道微生物群进行特征描述，以期能够针对肠道微生物群，减少实验中使用的动物数量。雄性B6.V-Lep(ob)/J小鼠根据与T2DM、炎症和肠道微生物群相关的一些特征进行表征。此后，所有结果在一个线性回归模型中相互关联。总的肠道微生物群谱与糖化血红蛋白相关，普雷沃氏菌科和毛螺菌科的高比例分别与葡萄糖耐量受损或改善相关。此外，随着葡萄糖耐量恶化，嗜黏蛋白阿克曼氏菌随年龄增长而消失。高比例的调节性T细胞与肠道微生物群相关，并改善了葡萄糖耐量。此外，高水平的白细胞介素-10、白细胞介素-12和肿瘤坏死因子-α与葡萄糖耐量受损、血糖或糖化血红蛋白相关。这些发现表明，肠道微生物群可能导致B6.V-Lep(ob)/J模型中各种疾病读数的变异，在B6.V-Lep(ob)/J模型的质量保证和数据评估中考虑它们可能会减少个体间的变异。
