Commercial rodent diets differentially regulate autoimmune glomerulonephritis, epigenetics and microbiota in MRL/lpr mice
Commercial rodent diets differentially regulate autoimmune glomerulonephritis, epigenetics and microbiota in MRL/lpr mice
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DOI：
10.1093/intimm/dxx033
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发表时间：
2017-06-01
影响因子：
4.4
通讯作者：
Ahmed, S. Ansar
中科院分区：
文献类型：
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作者：
Edwards, Michael R.;Dai, Rujuan;Ahmed, S. Ansar
自发性鼠狼疮模型中狼疮的病程和严重程度因实验室而异，这可能是由于饮食、住房和/或当地环境条件的变化。在这项研究中，我们调查了常见的啮齿动物饮食的影响，同时保持其他因素不变。将雌性狼疮易感MRL/lpr（MRL/MpJ-Fas（lpr）/J）小鼠置于相同的饲养条件下，并给予三种饲料之一：含富含孕酮的大豆和苜蓿的Teklad 7013、哈兰2018富含孕酮的大豆饲料或Research Diets Inc. D11112226（RD）含酪蛋白且不含植物雌激素的纯化成分饲料。虽然所有三个治疗组的总热量摄入量相似，但喂食2018饮食的小鼠出现了更高水平的蛋白尿，喂食7013或2018的小鼠出现了更高水平的肾小球免疫复合物沉积。值得注意的是，喂食RD饲料的小鼠蛋白尿明显减少，C3、总IgG、IgG 1和IgG 3免疫复合物沉积减少，沿着肾小球中CD 11 b（+）细胞浸润减少。饮食摄入的类型也影响细胞因子的产生，粪便微生物群（喂食2018的小鼠中毛螺菌科增加），改变的microRNA（miRNA;喂食7013和/或2018的小鼠中狼疮相关的miR-148 a和miR-183水平较高）和改变的DNA甲基化。这是第一项全面比较这些商业饮食对小鼠狼疮细胞、分子和表观遗传影响的研究。
The course and severity of lupus in spontaneous murine lupus models varies among laboratories, which may be due to variations in diet, housing and/or local environmental conditions. In this study, we investigated the influence of common rodent diets while keeping other factors constant. Female lupus-prone MRL/lpr (MRL/MpJ-Fas(lpr)/J) mice were subjected to the same housing conditions and given one of the three diets: Teklad 7013 containing isoflavone-rich soy and alfalfa, Harlan 2018 isoflavone-rich soy-based diet or Research Diets Inc. D11112226 (RD) purified-ingredients diet containing casein and no phytoestrogens. While the total caloric intake was similar among all three treatment groups, mice fed on the 2018 diet developed higher levels of proteinuria and mice fed on either 7013 or 2018 developed higher levels of glomerular immune complex deposition. Remarkably, mice fed the RD diet had markedly decreased proteinuria with diminished C3, total IgG, IgG1 and IgG3 immune complex deposition, along with reduced CD11b(+) cellular infiltration into the glomeruli. The type of diet intake also influenced cytokine production, fecal microbiota (increased Lachnospiraceae in mice fed on 2018), altered microRNAs (miRNAs; higher levels of lupus-associated miR-148a and miR-183 in mice fed on 7013 and/or 2018) and altered DNA methylation. This is the first study to comprehensively compare the cellular, molecular and epigenetic effects of these commercial diets in murine lupus.