Tyrosine supplement ameliorates murine aGVHD by modulation of gut microbiome and metabolome.
Tyrosine supplement ameliorates murine aGVHD by modulation of gut microbiome and metabolome.
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酪氨酸补充剂通过调节肠道微生物组和代谢组改善小鼠 aGVHD
DOI：
10.1016/j.ebiom.2020.103048
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发表时间：
2020-11
期刊：
影响因子：
11.1
通讯作者：
Huang H
中科院分区：
文献类型：
--
作者：
Li X;Lin Y;Li X;Xu X;Zhao Y;Xu L;Gao Y;Li Y;Tan Y;Qian P;Huang H
肠道微生物群落及其代谢成分对免疫稳态至关重要，并影响宿主对同种异体造血干细胞移植（alloo - hsct）后急性移植物抗宿主病（aGVHD）等多种免疫介导疾病的易感性。然而，由于胃肠道环境的复杂性，对aGVHD中微生物组和代谢组之间的功能联系知之甚少。首先，通过16S核糖体DNA基因测序和基于超高效液相色谱-质谱（UHPLC-MS）的代谢组学，研究了aGVHD小鼠模型的肠道微生物群和粪便代谢表型。aGVHD组未分类毛螺杆菌明显减少，但XI、XIVa和肠球菌的相对丰度增加。同时，aGVHD小鼠肠道中酪氨酸含量较低。相关性分析显示，酪氨酸相关代谢物与Clostridium XIVa呈负相关，Blautia和Enterococcus在aGVHD条件下也呈负相关。除了探索酪氨酸的重要性和功能外，在移植过程中给小鼠提供了不同的酪氨酸饮食。额外补充酪氨酸可以提高总生存率，改善aGVHD早期症状，改变肠道微生物群的结构和组成以及粪便代谢表型。此外，剥夺酪氨酸的aGVHD小鼠表现出比载体饮食组更差的表现。结果表明，肠道菌群、必需代谢物和酪氨酸在aGVHD进展中的作用和机制，可作为aGVHD诊断和治疗的潜在生物标志物。基金资助：国际合作与交流计划项目（81520108002）、国家重点研发计划项目（2018YFA0109300）、国家自然科学基金项目（81670169、81670148、81870080、91949115）、浙江省自然科学基金项目（LQ19H080006）。
Microbial communities and their metabolic components in the gut are of vital importance for immune homeostasis and have an influence on the susceptibility of the host to a number of immune-mediated diseases like acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the functional connections between microbiome and metabolome in aGVHD due to the complexity of the gastrointestinal environment. Initially, gut microbiota and fecal metabolic phenotype in aGVHD murine models were unleashed by performing 16S ribosomal DNA gene sequencing and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics. The group with aGVHD experienced a significant drop in Lachnospiraceae_unclassified but an increase in the relative abundance of Clostridium XI, Clostridium XIVa and Enterococcus. Meanwhile, a lower content of tyrosine was observed in the gut of aGVHD mice. The correlation analysis revealed that tyrosine-related metabolites were inversely correlated with Clostridium XIVa, besides, Blautia and Enterococcus also displayed the negative tendency in aGVHD condition. Apart from exploring the importance and function of tyrosine, different tyrosine diets were offered to mice during transplantation. Additional tyrosine supplements can improve overall survival, ameliorate symptoms at the early stage of aGVHD and change the structure and composition of gut microbiota and fecal metabolic phenotype. In addition, aGVHD mice deprived from tyrosine displayed worse manifestations than the vehicle diet group. The results demonstrated the roles and mechanisms of gut microbiota, indispensable metabolites and tyrosine in the progression of aGVHD, which can be an underlying biomarker for aGVHD diagnosis and treatment. This research was funded by the International Cooperation and Exchange Program (81520108002), the National Key R&D Program of China, Stem Cell and Translation Research (2018YFA0109300), National Natural Science Foundation of China (81670169, 81670148, 81870080 and 91949115) and Natural Science Foundation of Zhejiang Province (LQ19H080006).
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DOI：
10.1016/j.bbmt.2014.01.030
发表时间：
2014-05
期刊：
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
影响因子：
--
作者：
Holler E;Butzhammer P;Schmid K;Hundsrucker C;Koestler J;Peter K;Zhu W;Sporrer D;Hehlgans T;Kreutz M;Holler B;Wolff D;Edinger M;Andreesen R;Levine JE;Ferrara JL;Gessner A;Spang R;Oefner PJ
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Oefner PJ
影响因子：
30.5
作者：
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DOI：
10.1007/s00426-017-0957-4
发表时间：
2019-09
期刊：
Psychological research
影响因子：
--
作者：
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通讯作者：
Widaman KF
影响因子：
2.9
作者：
Lieberman, HR;Georgelis, JH;Yeghiayan, SK
通讯作者：
Yeghiayan, SK
DOI：
10.1084/jem.20112408
发表时间：
2012-05-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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通讯作者：
van den Brink MR