Induction and Amelioration of Methotrexate-Induced Gastrointestinal Toxicity are Related to Immune Response and Gut Microbiota.
Induction and Amelioration of Methotrexate-Induced Gastrointestinal Toxicity are Related to Immune Response and Gut Microbiota.
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甲氨蝶呤引起的胃肠道毒性的诱导和改善与免疫反应和肠道菌群有关
DOI：
10.1016/j.ebiom.2018.06.029
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发表时间：
2018-07
期刊：
影响因子：
11.1
通讯作者：
Yang L
中科院分区：
文献类型：
--
作者：
Zhou B;Xia X;Wang P;Chen S;Yu C;Huang R;Zhang R;Wang Y;Lu L;Yuan F;Tian Y;Fan Y;Zhang X;Shu Y;Zhang S;Bai D;Wu L;Xu H;Yang L
甲氨蝶呤（MTX）作为一种广泛应用的抗肿瘤和免疫抑制剂，可引起胃肠道毒性等多种药物不良反应，其机制尚不清楚。肠道菌群已被广泛报道与多种疾病的发作以及不同药物的治疗结果相关。在该研究中，在MTX处理的小鼠中观察到粘膜损伤，导致巨噬细胞的显著变化（即，M1/M2比值，P < 0.05），但在树突状细胞中没有。MTX处理后，小鼠肠道菌群的数量、多样性和主成分均发生显著变化，且呈时间依赖性，其中类杆菌的变化最为显著（P < 0.05）。脆弱类杆菌在MTX治疗后明显减少（P < 0.01），并随巨噬细胞密度的增加而减少。用B管饲小鼠。fragilis减轻MTX诱导的炎症反应并调节巨噬细胞极化。总之，我们的研究结果描述了肠道微生物群对MTX诱导的肠粘膜炎的强烈影响，并为预防此类ADR提供了潜在的方法。
As a widely used anticancer and immunosuppressive agent, methotrexate (MTX) can induce multiple adverse drug reactions (ADRs), such as gastrointestinal toxicity, the mechanisms are poorly understood. Gut microbiota has been widely reported to be associated with the onset of multiple diseases as well as treatment outcomes of different drugs. In this study, mucosal injury was observed in MTX-treated mice, leading to significant changes in macrophages (i.e., M1/M2 ratio, P < 0.05) but not in dendritic cells. Moreover, the population, diversity and principal components of the gut microbiota in mice were dramatically altered after MTX treatment in a time-dependent manner, and Bacteroidales exhibited the most distinct variation among all the taxa (P < 0.05). Bacteroides fragilis was significantly decreased with MTX treatment (P < 0.01) and tended to decrease proportionately with increasing macrophage density. Gavage of mice with B. fragilis ameliorated MTX-induced inflammatory reactions and modulate macrophage polarization. In conclusion, our results delineate a strong impact of the gut microbiota on MTX-induced intestinal mucositis and provide a potential method for the prevention of such ADRs.
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影响因子：
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作者：
Morsy MA;Ibrahim SA;Amin EF;Kamel MY;Rifaai RA;Hassan MK
通讯作者：
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氨磷汀对大剂量甲氨蝶呤所致小鼠小肠粘膜炎的保护作用
影响因子：
3.1
作者：
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作者：
Gautam R;Singh M;Gautam S;Rawat JK;Saraf SA;Kaithwas G
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Kaithwas G
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30.3
作者：
Littman DR;Pamer EG
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Pamer EG
影响因子：
64.5
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Levy M;Thaiss CA;Zeevi D;Dohnalová L;Zilberman-Schapira G;Mahdi JA;David E;Savidor A;Korem T;Herzig Y;Pevsner-Fischer M;Shapiro H;Christ A;Harmelin A;Halpern Z;Latz E;Flavell RA;Amit I;Segal E;Elinav E
通讯作者：
Elinav E