The autoimmune disease systemic lupus erythematosus (SLE) is characterized by the production of pathogenic autoantibodies. It has been postulated that gut microbial dysbiosis may be one of the mechanisms involved in SLE pathogenesis. Here, we demonstrate that the dysbiotic gut microbiota of triple congenic (TC) lupus-prone mice (B6.Sle1.Sle2.Sle3) stimulated the production of autoantibodies and activated immune cells when transferred into germfree congenic C57BL/6 (B6) mice. Fecal transfer to B6 mice induced autoimmune phenotypes only when the TC donor mice exhibited autoimmunity. Autoimmune pathogenesis was mitigated by horizontal transfer of the gut microbiota between co-housed lupus-prone TC mice and control congenic B6 mice. Metabolomic screening identified an altered distribution of tryptophan metabolites in the feces of TC mice including an increase in kynurenine, which was alleviated after antibiotic treatment. Low dietary tryptophan prevented autoimmune pathology in TC mice, whereas high dietary tryptophan exacerbated disease. Reducing dietary tryptophan altered gut microbial taxa in both lupus-prone TC mice and control B6 mice. Consequently, fecal transfer from TC mice fed a high tryptophan diet, but not a low tryptophan diet, induced autoimmune phenotypes in germfree B6 mice. The interplay of gut microbial dysbiosis, tryptophan metabolism and host genetic susceptibility in lupus-prone mice suggest that aberrant tryptophan metabolism may contribute to autoimmune activation in this disease.

自身免疫性疾病系统性红斑狼疮（SLE）的特征是产生致病性自身抗体。据推测，肠道微生物失调可能是 SLE 发病机制之一。在这里，我们证明，当三重同源 (TC) 狼疮易发小鼠 ( B6.Sle1.Sle2.Sle3 ) 转移到无菌同源 C57BL/6 (B6) 小鼠中时，其失调的肠道微生物群会刺激自身抗体的产生并激活免疫细胞。仅当 TC 供体小鼠表现出自身免疫时，粪便转移至 B6 小鼠才会诱导自身免疫表型。通过在共养的易患狼疮的 TC 小鼠和对照同源 B6 小鼠之间水平转移肠道微生物群，可以减轻自身免疫发病机制。代谢组学筛查发现 TC 小鼠粪便中色氨酸代谢物的分布发生改变，包括犬尿氨酸增加，但抗生素治疗后这种情况得到缓解。低饮食色氨酸可以预防 TC 小鼠的自身免疫病理，而高饮食色氨酸则加剧疾病。减少膳食色氨酸可以改变狼疮倾向 TC 小鼠和对照 B6 小鼠的肠道微生物分类群。因此，来自喂食高色氨酸饮食而非低色氨酸饮食的 TC 小鼠的粪便转移在无菌 B6 小鼠中诱导了自身免疫表型。易患狼疮的小鼠肠道微生物失调、色氨酸代谢和宿主遗传易感性之间的相互作用表明，异常的色氨酸代谢可能导致这种疾病的自身免疫激活。