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系统性红斑狼疮中具有强大干扰素生成特性的肠道病毒组紊乱

Disturbed gut virome with potent interferonogenic property in systemic lupus erythematosus.

作者信息

Chen Beidi, Cao Jiabao, Liu Wei, Zhang Yuqing, Liu Yudong, Wang Min, Xiao Fei, Ma Jie, Wang Jun, Zhang Xuan

机构信息

Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China; Division of Rheumatology and Immunology, Peking University Third Hospital, Beijing 100191, China.

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100101, China.

出版信息

Sci Bull (Beijing). 2023 Feb 15;68(3):295-304. doi: 10.1016/j.scib.2023.01.021. Epub 2023 Jan 18.

Abstract

Accumulating evidence suggests an essential role of disturbed gut microbiota in the etiopathogenesis of systemic lupus erythematosus (SLE), but it remains unclear as to gut virome. In this study, fecal virus-like particles (VLPs) isolated from 76 non-treated SLE patients and 75 healthy controls were subjected to gut virome profiling. The proportion of bacteriophages was significantly elevated in the SLE gut, and the altered viral taxa were correlated with clinical parameters. Gut virome and bacteriome were closely associated with each other in SLE patients. The combination of gut viral and bacterial markers displayed better performance in distinguishing SLE patients from healthy controls. Further, VLPs from non-treated SLE patients promoted interferon-α production in an epithelial cell line and human immune cells. Intriguingly, the interferon-stimulatory capacity diminished in VLPs from post-treated SLE patients. Our findings may shed novel insights into SLE pathogenesis. Further in-depth understanding of gut virome might help develop future biomarkers and therapeutics for SLE patients.

摘要

越来越多的证据表明,肠道微生物群紊乱在系统性红斑狼疮(SLE)的发病机制中起着至关重要的作用,但肠道病毒组的情况仍不清楚。在本研究中,从76例未治疗的SLE患者和75例健康对照中分离出的粪便病毒样颗粒(VLP)进行了肠道病毒组分析。SLE患者肠道中噬菌体的比例显著升高,病毒分类群的改变与临床参数相关。在SLE患者中,肠道病毒组和细菌组彼此密切相关。肠道病毒和细菌标志物的组合在区分SLE患者和健康对照方面表现更好。此外,未治疗的SLE患者的VLP在上皮细胞系和人类免疫细胞中促进了干扰素-α的产生。有趣的是,治疗后的SLE患者的VLP的干扰素刺激能力减弱。我们的发现可能为SLE的发病机制提供新的见解。对肠道病毒组的进一步深入了解可能有助于为SLE患者开发未来的生物标志物和治疗方法。

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