Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, The Ministry of Education Key Laboratory, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuai-Fu-Yuan, Dong-Cheng District, Beijing, 100730, China.
National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID); State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH), 41 Damucang Hutong, Xicheng District, Beijing, 100730, China.
Curr Rheumatol Rep. 2021 Apr 16;23(4):27. doi: 10.1007/s11926-021-00986-z.
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that typically displays chronic inflammatory tissue damage and miscellaneous circulatory autoantibodies, as well as distinctive type 1 interferon signatures. The etiology of SLE is unclear and currently is attributed to genetic predisposition and environmental triggers. Gut microbiota has recently been considered a critical environmental pathogenic factor in immune-related disorders, and studies are ongoing to uncover the key pathogens and the imputative mechanisms. Fundamental advancements on the role of the microbiota in SLE pathology have been achieved in recent years and are summarized in this review.
Recent findings suggested that gut commensals could propagate autoimmunity via molecular mimicry in which ortholog-carrying microbes cross-activate autoreactive T/B cells and trigger the response against host autoantigens, or via bystander activation by stimulating antigen-presenting cells that present autoantigens and enhancing the expression of co-stimulatory molecules and cytokines, thus leading to the loss of self-tolerance and the production of autoantibodies. Additionally, the break of gut barrier and the translocation of gut commensals to inner organs can trigger immune dysregulation and inappropriate systemic inflammation. All these microbiota-mediated mechanisms could contribute to lupus immunopathogenesis and promote disease development in susceptible individuals. Evidence of the causative role of disturbed gut microbiome in SLE is still limited, and the related molecular mechanisms and pathways are largely elusive. However, the modification of gut microbiota, such as pathobiont vaccine, special diet, restricted consortium transplantation, as well as regulatory metabolites supplementation, might be promising strategies for lupus prophylaxis and treatment.
系统性红斑狼疮（SLE）是一种典型的自身免疫性疾病，通常表现为慢性炎症性组织损伤和各种循环自身抗体，以及独特的 1 型干扰素特征。SLE 的病因尚不清楚，目前归因于遗传易感性和环境触发因素。肠道微生物群最近被认为是与免疫相关疾病相关的关键环境致病因素，目前正在进行研究以揭示关键病原体和归因机制。近年来，在微生物群在 SLE 发病机制中的作用方面取得了重大进展，本综述对此进行了总结。
最近的研究结果表明，肠道共生菌可能通过分子模拟在其中携带同源物的微生物交叉激活自身反应性 T/B 细胞并引发针对宿主自身抗原的反应，或通过刺激呈递自身抗原并增强共刺激分子和细胞因子表达的抗原呈递细胞的旁路激活来引发自身免疫，从而导致自身耐受的丧失和自身抗体的产生。此外，肠道屏障的破坏和肠道共生菌向内脏器官的易位可引发免疫失调和不适当的全身炎症。所有这些由微生物群介导的机制都可能导致狼疮免疫发病机制，并促进易感个体的疾病发展。肠道微生物群紊乱在 SLE 中的因果作用证据仍然有限，相关的分子机制和途径在很大程度上还不清楚。然而，肠道微生物群的修饰，如病原菌疫苗、特殊饮食、受限 consortium 移植以及调节代谢物的补充，可能是狼疮预防和治疗的有前途的策略。
