Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients.
Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients.
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DOI：
10.1038/srep24072
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发表时间：
2016-04-05
影响因子：
4.6
通讯作者：
Suárez A
中科院分区：
文献类型：
--
作者：
López P;de Paz B;Rodríguez-Carrio J;Hevia A;Sánchez B;Margolles A;Suárez A
系统性红斑狼疮（SLE）患者中曾报告过以厚壁菌门/拟杆菌门比例降低为特征的肠道生态失调。在这项研究中，体外培养显示，从SLE患者粪便样本（SLE-M）中分离的微生物群比健康对照微生物群更大程度地促进淋巴细胞活化和幼稚CD 4+淋巴细胞的Th 17分化。用Treg诱导细菌富集SLE-M显示，两种梭菌菌株的混合物显著降低了Th 17/Th 1平衡，而两歧双歧杆菌补充剂防止了CD 4+淋巴细胞过度活化，从而支持含有Treg诱导菌株的益生菌的可能治疗益处，以恢复SLE中存在的Treg/Th 17/Th 1失衡。事实上，患者样品的离体分析显示出扩大的Th 17和Foxp 3 + IL-17+群体，表明可能的Treg-Th 17转分化。此外，粪便微生物群分析显示，健康对照组中IL-17+群体与厚壁菌门之间呈负相关，而在SLE中，该门与IFNγ的血清水平直接相关，IFN γ是一种Th 1细胞因子，在患者中略有降低。最后，协同菌的频率，与厚壁菌/拟杆菌的比例在健康对照组中呈正相关，往往会减少患者时，抗dsDNA滴度增加，并表现出强烈的负相关性与IL-6血清水平和保护性天然IgM抗体对磷酸胆碱呈正相关。
Intestinal dysbiosis, characterized by a reduced Firmicutes/Bacteroidetes ratio, has been reported in systemic lupus erythematosus (SLE) patients. In this study, in vitro cultures revealed that microbiota isolated from SLE patient stool samples (SLE-M) promoted lymphocyte activation and Th17 differentiation from naïve CD4+ lymphocytes to a greater extent than healthy control-microbiota. Enrichment of SLE-M with Treg-inducing bacteria showed that a mixture of two Clostridia strains significantly reduced the Th17/Th1 balance, whereas Bifidobacterium bifidum supplementation prevented CD4+ lymphocyte over-activation, thus supporting a possible therapeutic benefit of probiotics containing Treg-inducer strains in order to restore the Treg/Th17/Th1 imbalance present in SLE. In fact, ex vivo analyses of patient samples showed enlarged Th17 and Foxp3+ IL-17+ populations, suggesting a possible Treg-Th17 trans-differentiation. Moreover, analyses of fecal microbiota revealed a negative correlation between IL-17+ populations and Firmicutes in healthy controls, whereas in SLE this phylum correlated directly with serum levels of IFNγ, a Th1 cytokine slightly reduced in patients. Finally, the frequency of Synergistetes, positively correlated with the Firmicutes/Bacteroidetes ratio in healthy controls, tended to be reduced in patients when anti-dsDNA titers were increased and showed a strong negative correlation with IL-6 serum levels and correlated positively with protective natural IgM antibodies against phosphorylcholine.