Pharmacologic inhibition of glycolysis prevents the development of lupus by altering the gut microbiome in mice.
Pharmacologic inhibition of glycolysis prevents the development of lupus by altering the gut microbiome in mice.
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DOI：
10.1016/j.isci.2023.107122
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发表时间：
2023-07-21
期刊：
影响因子：
5.8
通讯作者：
Morel, Laurence
中科院分区：
文献类型：
--
作者：
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
肠道生态失调与狼疮发病机制相关，并且来自狼疮易感小鼠的粪便微生物群转移（FMT）显示出诱导健康小鼠的自身免疫激活。狼疮患者的免疫细胞表现出增加的葡萄糖代谢，并且用糖酵解抑制剂2-脱氧-D-葡萄糖（2DG）治疗在狼疮易感小鼠中是治疗性的。在这里，我们在两种不同病因的狼疮模型中发现，2DG改变了粪便微生物组和相关代谢物的组成。在这两种模型中，与对照小鼠的FMT相比，2DG处理小鼠的FMT保护相同品系的狼疮易感小鼠免于肾小球肾炎的发展，减少自身抗体产生以及CD 4 + T细胞和骨髓细胞的活化。因此，我们证明了狼疮中葡萄糖抑制的保护作用可以通过肠道微生物群转移，直接将免疫代谢的改变与宿主的肠道生态失调联系起来。狼疮小鼠的肠道微生物群将自身免疫激活转移到正常小鼠中用2DG抑制糖酵解逆转狼疮小鼠中的自身免疫激活2DG改变了狼疮小鼠微生物组的组成和代谢组2DG治疗小鼠的粪便微生物转移阻止了狼疮的发展制药科学;免疫系统疾病;微生物组
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. Gut microbiota from lupus mice transferred autoimmune activation into normal mice Inhibition of glycolysis with 2DG reversed autoimmune activation in lupus mice 2DG altered the composition and the metabolome of the microbiome of lupus mice Fecal microbial transfers from 2DG treated mice prevented lupus development Pharmaceutical science; Immune system disorder; Microbiome
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影响因子：
16.6
作者：
Choi SC;Titov AA;Abboud G;Seay HR;Brusko TM;Roopenian DC;Salek-Ardakani S;Morel L
通讯作者：
Morel L
影响因子：
64.5
作者：
Kawano, Yoshinaga;Edwards, Madeline;Huang, Yiming;Bilate, Angelina M.;Araujo, Leandro P.;Tanoue, Takeshi;Atarashi, Koji;Ladinsky, Mark S.;Reiner, Steven L.;Wang, Harris H.;Mucida, Daniel;Honda, Kenya;Ivanov, Ivaylo I.
通讯作者：
Ivanov, Ivaylo I.
影响因子：
--
作者：
Lai, Zhi-Wei;Hanczko, Robert;Bonilla, Eduardo;Caza, Tiffany N.;Clair, Brandon;Bartos, Adam;Miklossy, Gabriella;Jimah, John;Doherty, Edward;Tily, Hajra;Francis, Lisa;Garcia, Ricardo;Dawood, Maha;Yu, Jianghong;Ramos, Irene;Coman, Ioana;Faraone, Stephen V.;Phillips, Paul E.;Perl, Andras
通讯作者：
Perl, Andras
影响因子：
7.3
作者：
Bagavant H;Araszkiewicz AM;Ingram JK;Cizio K;Merrill JT;Arriens C;Guthridge JM;James JA;Deshmukh US
通讯作者：
Deshmukh US
影响因子：
4.6
作者：
Kverka, M.;Zakostelska, Z.;Tlaskalova-Hogenova, H.
通讯作者：
Tlaskalova-Hogenova, H.