Department of Rheumatology, Clinical Immunology Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science, and Peking Union Medical College, Beijing, China.
Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Beijing, China.
Arthritis Rheumatol. 2021 Feb;73(2):232-243. doi: 10.1002/art.41511. Epub 2020 Dec 29.
Changes in gut microbiota have been linked to systemic lupus erythematosus (SLE), but knowledge is limited. Our study aimed to provide an in-depth understanding of the contribution of gut microbiota to the immunopathogenesis of SLE.
Fecal metagenomes from 117 patients with untreated SLE and 52 SLE patients posttreatment were aligned with 115 matched healthy controls and analyzed by whole-genome profiling. For comparison, we assessed the fecal metagenome of MRL/lpr mice. The oral microbiota origin of the gut species that existed in SLE patients was documented by single-nucleotide polymorphism-based strain-level analyses. Functional validation assays were performed to demonstrate the molecular mimicry of newly found microbial peptides.
Gut microbiota from individuals with SLE displayed significant differences in microbial composition and function compared to healthy controls. Certain species, including the Clostridium species ATCC BAA-442 as well as Atopobium rimae, Shuttleworthia satelles, Actinomyces massiliensis, Bacteroides fragilis, and Clostridium leptum, were enriched in SLE gut microbiota and reduced after treatment. Enhanced lipopolysaccharide biosynthesis aligned with reduced branched chain amino acid biosynthesis was observed in the gut of SLE patients. The findings in mice were consistent with our findings in human subjects. Interestingly, some species with an oral microbiota origin were enriched in the gut of SLE patients. Functional validation assays demonstrated the proinflammatory capacities of some microbial peptides derived from SLE-enriched species.
This study provides detailed information on the microbiota of untreated patients with SLE, including their functional signatures, similarities with murine counterparts, oral origin, and the definition of autoantigen-mimicking peptides. Our data demonstrate that microbiome-altering approaches may offer valuable adjuvant therapies in SLE.
肠道微生物群的变化与系统性红斑狼疮（SLE）有关，但相关知识有限。本研究旨在深入了解肠道微生物群对 SLE 免疫发病机制的贡献。
对 117 例未经治疗的 SLE 患者和 52 例治疗后 SLE 患者的粪便宏基因组进行了全基因组分析，并与 115 例匹配的健康对照进行了分析。为了进行比较，我们评估了 MRL/lpr 小鼠的粪便宏基因组。通过基于单核苷酸多态性的菌株水平分析，记录了存在于 SLE 患者中的肠道物种的口腔微生物群起源。进行功能验证实验以证明新发现的微生物肽的分子模拟。
与健康对照组相比，SLE 患者的肠道微生物群在微生物组成和功能上存在显著差异。某些物种，包括 Clostridium 物种 ATCC BAA-442 以及 Atopobium rimae、Shuttleworthia satelles、Actinomyces massiliensis、Bacteroides fragilis 和 Clostridium leptum，在 SLE 肠道微生物群中富集，并在治疗后减少。在 SLE 患者的肠道中观察到增强的内毒素生物合成与减少的支链氨基酸生物合成一致。在小鼠中的发现与我们在人类受试者中的发现一致。有趣的是，一些具有口腔微生物群起源的物种在 SLE 患者的肠道中富集。功能验证实验证明了一些源自 SLE 富集物种的微生物肽具有促炎能力。
本研究提供了未经治疗的 SLE 患者的详细微生物组信息，包括其功能特征、与小鼠对应物的相似性、口腔起源和自身抗原模拟肽的定义。我们的数据表明，微生物组改变方法可能为 SLE 提供有价值的辅助治疗方法。
