BACKGROUND Dysbiosis of gut microbiota exists in the pathogenesis of many autoimmune diseases, including systemic lupus erythematosus (lupus). Lupus patients who experienced pregnancy usually had more severe disease flares post-delivery. However, the possible role of gut microbiota in the link between pregnancy and exacerbation of lupus remains to be explored. RESULTS In the classical lupus mouse model MRL/lpr, we compared the structures of gut microbiota in pregnant and lactating individuals vs. age-matched naïve mice. Consistent with studies on non-lupus mice, both pregnancy and lactation significantly changed the composition and diversity of gut microbiota. Strikingly, modulation of gut microbiota using the same strategy resulted in different disease outcomes in postpartum (abbreviated as "PP," meaning that the mice had undergone pregnancy and lactation) vs. control (naïve; i.e., without pregnancy or lactation) MRL/lpr females; while vancomycin treatment attenuated lupus in naïve mice, it did not do so, or even exacerbated lupus, in PP mice. Lactobacillus animalis flourished in the gut upon vancomycin treatment, and direct administration of L. animalis via oral gavage recapitulated the differential effects of vancomycin in PP vs. control mice. An enzyme called indoleamine 2,3-dioxygenase was significantly inhibited by L. animalis; however, this inhibition was only apparent in PP mice, which explained, at least partially, the lack of beneficial response to vancomycin in these mice. The differential production of immunosuppressive IL-10 and proinflammatory IFNγ in PP vs. control mice further explained why the disease phenotypes varied between the two types of mice bearing the same gut microbiota remodeling strategy. CONCLUSIONS These results suggest that pregnancy and lactation interfere with the response of autoimmunity to modulation of gut microbiota. Further studies are necessary to better understand the complex relationship between pregnancy and lupus.

中文翻译：

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怀孕和哺乳会干扰自身免疫对肠道菌群调节的反应。

背景技术肠道菌群失调存在于许多自身免疫性疾病的发病机理中，包括系统性红斑狼疮（狼疮）。经历过怀孕的狼疮患者通常在分娩后有更严重的疾病发作。然而，肠道菌群在妊娠与狼疮恶化之间的联系中可能发挥的作用尚待探索。结果在经典的狼疮小鼠模型MRL / lpr中，我们比较了妊娠和哺乳期个体与年龄相匹配的幼稚小鼠的肠道菌群结构。与对非狼疮小鼠的研究一致，妊娠和哺乳均显着改变了肠道菌群的组成和多样性。令人惊讶的是，使用相同的策略调节肠道菌群会导致产后不同的疾病结局（缩写为“ PP” 意思是小鼠已经过妊娠和哺乳）与对照组（未进行过实验，即没有妊娠或哺乳）MRL / lpr雌性；万古霉素治疗可使幼稚小鼠的狼疮减毒，但对PP小鼠却没有这样做，甚至加重了狼疮。万古霉素治疗后，动物乳酸杆菌在肠道中旺盛生长，通过口服管饲法直接施用动物乳杆菌可概括出万古霉素在PP与对照小鼠中的差异作用。动物乳杆菌明显抑制了一种名为吲哚胺2，3-二加氧酶的酶。但是，这种抑制作用仅在PP小鼠中明显，这至少部分地解释了这些小鼠对万古霉素缺乏有益反应。与PP相比，PP中免疫抑制性IL-10和促炎性IFNγ的差异产生。对照小鼠进一步解释了为什么在具有相同肠道微生物群重塑策略的两种类型的小鼠之间疾病表型不同。结论这些结果表明，妊娠和哺乳会干扰自身免疫对肠道菌群调节的反应。为了更好地了解妊娠与狼疮之间的复杂关系，有必要进行进一步的研究。