Elshikha Ahmed S, Ge Yong, Brown Josephine, Kanda Nathalie, Zadeh Mojgan, Abboud Georges, Choi Seung-Chul, Silverman Gregg, Garrett Timothy J, Clapp William L, Mohamadzadeh Mansour, Morel Laurence
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.
The Laboratory of B Cell Immunobiology and the Division of Rheumatology, NYU School of Medicine, New York, NY 10016, USA.
iScience. 2023 Jun 14;26(7):107122. doi: 10.1016/j.isci.2023.107122. eCollection 2023 Jul 21.
Gut dysbiosis has been associated with lupus pathogenesis, and fecal microbiota transfers (FMT) from lupus-prone mice shown to induce autoimmune activation into healthy mice. The immune cells of lupus patients exhibit an increased glucose metabolism and treatments with 2-deoxy-D-glucose (2DG), a glycolysis inhibitor, are therapeutic in lupus-prone mice. Here, we showed in two models of lupus with different etiologies that 2DG altered the composition of the fecal microbiome and associated metabolites. In both models, FMT from 2DG-treated mice protected lupus-prone mice of the same strain from the development of glomerulonephritis, reduced autoantibody production as well as the activation of CD4 T cells and myeloid cells as compared to FMT from control mice. Thus, we demonstrated that the protective effect of glucose inhibition in lupus is transferable through the gut microbiota, directly linking alterations in immunometabolism to gut dysbiosis in the hosts.
肠道微生物群失调与狼疮发病机制有关，将易患狼疮小鼠的粪便微生物群移植（FMT）到健康小鼠体内可诱导自身免疫激活。狼疮患者的免疫细胞表现出葡萄糖代谢增加，使用糖酵解抑制剂2-脱氧-D-葡萄糖（2DG）进行治疗对易患狼疮的小鼠具有治疗作用。在此，我们在两种不同病因的狼疮模型中表明，2DG改变了粪便微生物群的组成和相关代谢物。在这两种模型中，与来自对照小鼠的FMT相比，来自2DG处理小鼠的FMT可保护同品系的易患狼疮小鼠免受肾小球肾炎的发展，减少自身抗体的产生以及CD4 T细胞和髓样细胞的激活。因此，我们证明了狼疮中葡萄糖抑制的保护作用可通过肠道微生物群传递，将免疫代谢的改变与宿主肠道微生物群失调直接联系起来。
