Constipation induced gut microbiota dysbiosis exacerbates experimental autoimmune encephalomyelitis in C57BL/6 mice.
Constipation induced gut microbiota dysbiosis exacerbates experimental autoimmune encephalomyelitis in C57BL/6 mice.
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DOI：
10.1186/s12967-021-02995-z
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发表时间：
2021-07-23
影响因子：
7.4
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Lin X;Liu Y;Ma L;Ma X;Shen L;Ma X;Chen Z;Chen H;Li D;Su Z;Chen X
Constipation is a common gastrointestinal dysfunction which has a potential impact on people's immune state and their quality of life. Here we investigated the effects of constipation on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Constipation was induced by loperamide in female C57BL/6 mice. The alternations of gut microbiota, permeability of intestinal barrier and blood–brain barrier, and histopathology of colon were assessed after constipation induction. EAE was induced in the constipation mice. Fecal microbiota transplantation (FMT) was performed from constipation mice into microbiota-depleted mice. Clinical scores, histopathology of inflammation and demyelination, Treg/Th17 and Treg17/Teff17 imbalance both in the peripheral lymphatic organs and central nervous system, cytokines include TGF-β, GM-CSF, IL-10, IL-17A, IL-17F, IL-21, IL-22, and IL-23 in serum were assessed in different groups. Compared with the vehicle group, the constipation mice showed gut microbiota dysbiosis, colon inflammation and injury, and increased permeability of intestinal barrier and blood–brain barrier. We found that the clinical and pathological scores of the constipation EAE mice were severer than that of the EAE mice. Compared with the EAE mice, the constipation EAE mice showed reduced percentage of Treg and Treg17 cells, increased percentage of Th17 and Teff17 cells, and decreased ratio of Treg/Th17 and Treg17/Teff17 in the spleen, inguinal lymph nodes, brain, and spinal cord. Moreover, the serum levels of TGF-β, IL-10, and IL-21 were decreased while the GM-CSF, IL-17A, IL-17F, IL-22, and IL-23 were increased in the constipation EAE mice. In addition, these pathological processes could be transferred via their gut microbiota. Our results verified that constipation induced gut microbiota dysbiosis exacerbated EAE via aggravating Treg/Th17 and Treg17/Teff17 imbalance and cytokines disturbance in C57BL/6 mice. The online version contains supplementary material available at 10.1186/s12967-021-02995-z.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
长期饮用不含咖啡因的高蔗糖可乐饮料会加重小鼠EAE的发病。
影响因子：
33.5
作者：
Cao G;Wang Q;Huang W;Tong J;Ye D;He Y;Liu Z;Tang X;Cheng H;Wen Q;Li D;Chau HT;Wen Y;Zhong H;Meng Z;Liu H;Wu Z;Zhao L;Flavell RA;Zhou H;Xu A;Yang H;Yin Z
通讯作者：
Yin Z
影响因子：
5.2
作者：
Hosseinzadeh, A.;Baneshi, M. R.;Haghdoost, A. A.
通讯作者：
Haghdoost, A. A.
影响因子：
5.4
作者：
Kaskow, Belinda J.;Baecher-Allan, Clare
通讯作者：
Baecher-Allan, Clare
影响因子：
5.4
作者：
Huss, David J.;Winger, Ryan C.;Cox, Gina Mavrikis;Guerau-De-Arellano, Mireia;Yang, Yuhong;Racke, Michael K.;Lovett-Racke, Amy E.
通讯作者：
Lovett-Racke, Amy E.