Gut microbiota dysbiosis and altered tryptophan catabolism contribute to autoimmunity in lupus-susceptible mice.
Gut microbiota dysbiosis and altered tryptophan catabolism contribute to autoimmunity in lupus-susceptible mice.
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肠道微生物群失调和色氨酸分解代谢改变导致狼疮易感小鼠的自身免疫。
DOI：
10.1126/scitranslmed.aax2220
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发表时间：
2020-07-08
影响因子：
17.1
通讯作者：
Morel L
中科院分区：
文献类型：
--
作者：
Choi SC;Brown J;Gong M;Ge Y;Zadeh M;Li W;Croker BP;Michailidis G;Garrett TJ;Mohamadzadeh M;Morel L
自身免疫性疾病系统性红斑狼疮（SLE）的致病机制仍然是难以捉摸的。然而，肠道微生物群的生态失调可能参与疾病的发病机制。我们证明，当转移到非自身免疫无菌野生型小鼠中时，狼疮易感小鼠的肠道微生物群失调会诱导自身免疫。在狼疮易感小鼠中观察到色氨酸代谢产物犬尿氨酸的增加，抗生素治疗后犬尿氨酸减少。低饮食色氨酸预防自身免疫病理，而高饮食色氨酸加重疾病。此外，饮食中色氨酸的减少导致狼疮易感小鼠和同类正常对照小鼠肠道微生物类群的变化。肠道微生物生态失调、色氨酸代谢和宿主遗传易感性的相互作用表明，狼疮易感小鼠中色氨酸代谢异常可能是导致该疾病中自身免疫激活的机制之一。肠道微生物群失调通过改变色氨酸代谢诱导小鼠狼疮样自身免疫基因、微生物群和色氨酸控制自身免疫的相互作用肠道微生物群的改变可能通过细菌介导的免疫失调促进自身免疫。色氨酸是一种必需氨基酸，在犬尿氨酸生物合成中起关键作用。在狼疮患者和狼疮易感小鼠中观察到高犬尿氨酸。Choi等人在狼疮易感小鼠中发现的肠道细菌生态失调如何失调色氨酸代谢，这反过来又加剧了疾病的进展。他们还证明，自身免疫可以通过减少饮食中的色氨酸来减轻。因此，他们提出了一种模型，其中遗传易感性诱导自身免疫，导致肠道细菌生态失调和色氨酸代谢增加，从而增强宿主的狼疮发病机制。
Pathogenic mechanisms involved in the autoimmune disorder systemic lupus erythematosus (SLE) remain elusive. However, dysbiosis of the gut microbiota may be involved in disease pathogenesis. We demonstrate that the dysbiotic gut microbiota of lupus-prone mice induced autoimmunity when transferred into non-autoimmune germfree wildtype mice. An increase in kynurenine, a metabolite of tryptophan metabolism, was observed in lupus-prone mice, which decreased after antibiotic treatment. Low dietary tryptophan prevented autoimmune pathology, whereas high dietary tryptophan exacerbated disease. Further, a reduction in dietary tryptophan resulted in changes in gut microbial taxa in lupus-prone mice and the congenic normal control mice. The interplay of gut microbial dysbiosis, tryptophan metabolism and host genetic susceptibility suggested that aberrant tryptophan metabolism in lupus-susceptible mice could be one of the mechanisms contributing to autoimmune activation in this disease. Gut microbiota dysbiosis induces lupus-like autoimmunity in mice through altered tryptophan metabolism Interplay of genes, microbiome, and tryptophan controls autoimmunity Alterations in gut microbiota may contribute to autoimmunity through bacterial-mediated immune dysregulations. Tryptophan, an essential amino acid, is critically involved in kynurenine biosynthesis. High kynurenine is observed in patients with lupus and lupus-prone mice. Choi et al. how that gut bacterial dysbiosis found in lupus-prone mice dysregulates tryptophan metabolism, which, in turn, exacerbates the disease progression. They also demonstrate that autoimmunity can be mitigated by reducing dietary tryptophan. Thus, they propose a model in which genetic susceptibility induces autoimmunity, which leads to gut bacterial dysbiosis and an increased tryptophan metabolism that enhances lupus pathogenesis in the host.
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DOI：
10.1038/nrrheum.2012.58
发表时间：
2012-05-01
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
通讯作者：
--
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：
5
作者：
Cuda, C. M.;Zeumer, L.;Sobel, E. S.;Croker, B. P.;Morel, L.
通讯作者：
Morel, L.
影响因子：
15.9
作者：
Colliou, Natacha;Ge, Yong;Mohamadzadeh, Mansour
通讯作者：
Mohamadzadeh, Mansour
影响因子：
32.4
作者：
Gutiérrez-Vázquez C;Quintana FJ
通讯作者：
Quintana FJ