Helminth-Based Product and the Microbiome of Mice with Lupus
Helminth-Based Product and the Microbiome of Mice with Lupus
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DOI：
10.1128/msystems.00160-18
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发表时间：
2019-01-01
期刊：
影响因子：
6.4
通讯作者：
Koren, Omry
中科院分区：
文献类型：
--
作者：
Neuman, Hadar;Mor, Hadar;Koren, Omry
卫生假说声称，发达国家缺乏微生物接触与自身免疫性疾病发病率的上升有关。研究还发现，蠕虫能够调节宿主的免疫反应以存活。因此，已经报道了使用蠕虫作为自身免疫性患者的治疗的几个成功的试验。蠕虫的衍生物，磷酸胆碱（PC），被发现作为一种免疫调节分子。我们最近在小鼠模型中显示，当在肾小球肾炎发作前给予称为TPC的tuftsin和PC的缀合物时，其减弱系统性红斑狼疮（SLE）的发展。目前的研究旨在检查TPC对狼疮小鼠模型中肠道微生物组的影响。TPC治疗改变了活动性狼疮小鼠的肠道组成，与肾小球肾炎显著减少相关，随后抗炎性白细胞介素10（IL-10）水平升高，促炎介质水平降低，调节性T细胞群扩增。重要的是，我们发现TPC治疗改变了小鼠肠道微生物组的组成，与蛋白质分泌的显著减少和疾病参数的改善相关。TPC处理对肠道微生物组的主要影响包括阿克曼氏菌丰度降低和几个属丰度增加，包括Turicibacter、双歧杆菌、未分类的Mogibacteriaceae、未分类的Clostridiaceae、Adlercreutzia、Allobaculum和Anaeroplasma。总的来说，我们的研究结果与微生物的变化与免疫调节的肾小球肾炎小鼠lupus.IMPORTANCE最近，几篇论文提到了不同的细菌与狼疮在小鼠和人类的协会。这是第一份证明蠕虫衍生化合物对狼疮小鼠诱导缓解的作用及其与细菌变化的关系的报告。我们发现，几个属，包括阿克曼氏，与临床和血清学参数的狼疮，而其他属，包括丁酸产生菌，与改善疾病后tuftsin和磷酸胆碱治疗。
The hygiene hypothesis claims that the lack of exposure to microorganisms in developed countries correlates with a rise in the incidence of autoimmune diseases. It was also found that helminths are able to modulate the immune response in hosts in order to survive. Consequently, several successful trials using helminths as a treatment for autoimmune patients have been reported. The helminth derivative, phosphorylcholine (PC), was discovered as an immunomodulatory molecule. We have recently shown in a murine model that when a conjugate of tuftsin and PC, termed TPC, is prophylactically administered before the onset of glomerulonephritis, it attenuates the development of systemic lupus erythematosus (SLE). The current study aimed to examine the TPC effect on the gut microbiome in a mouse model of lupus. TPC treatment altered the gut composition in the mice with active lupus, in correlation with a significant decrease in glomerulonephritis, followed by an increased level of anti-inflammatory interleukin 10 (IL-10), decreased levels of proinflammatory mediators, and expansion of the T regulatory cell population. Importantly, we found that TPC treatment altered the mouse gut microbiome composition, in correlation with a significant decrease in protein secretion and improved disease parameters. The major effects of TPC treatment on the gut microbiome included decreased abundances of Akkermansia and increased abundance of several genera, including Turicibacter, Bifidobacterium, unclassified Mogibacteriaceae, unclassified Clostridiaceae, Adlercreutzia, Allobaculum, and Anaeroplasma. Overall, our results associate microbial changes with the immunomodulation of glomerulonephritis in mice with lupus.IMPORTANCE Recently, several papers referred to the association of different bacteria with lupus in mice and humans. This is the first report to demonstrate the effect of a compound derived from helminths on the induction of remission in mice with lupus and its association with a bacterial change. We show that several genera, including Akkermansia, are associated with clinical and serological parameters of lupus, while other genera, including butyrate-producing bacteria, are associated with amelioration of disease following tuftsin and phosphorylcholine treatment.