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原发性干燥综合征初治患者肠道微生物群的组成和功能异常。

Compositional and functional aberrance of the gut microbiota in treatment naïve patients with primary Sjögren's syndrome.

作者信息

Jia Xin-Miao, Wu Bing-Xuan, Chen Bei-di, Li Ke-Tian, Liu Yu-Dong, Xu Yue, Wang Jun, Zhang Xuan

机构信息

Medical Research Center, Peking Union Medical College Hospital; Department of Rheumatology, Beijing Hospital, National Center of Gerontology; Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.

State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China; Department of Rheumatology and Immunology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.

出版信息

J Autoimmun. 2022 Nov 28;134:102958. doi: 10.1016/j.jaut.2022.102958.

DOI:10.1016/j.jaut.2022.102958
PMID:36455385
Abstract

OBJECTIVES

To investigate the compositional and functional characteristics of the gut microbiota in primary Sjögren's syndrome (pSS) and compare them with those in systemic lupus erythematosus (SLE).

METHODS

Stool samples from 78 treatment naïve pSS patients and 78 matched healthy controls were detected by shotgun metagenomic sequencing and compared with those from 49 treatment naïve SLE patients. The virulence loads and mimotopes of the gut microbiota were also assessed by sequence alignment.

RESULTS

The gut microbiota of treatment naïve pSS patients had lower richness and evenness and showed a different community distribution than that of healthy controls. The microbial species enriched in the pSS-associated gut microbiota included Lactobacillus salivarius, Bacteroides fragilis, Ruminococcus gnavus, Clostridium bartlettii, Clostridium bolteae, Veillonella parvula, and Streptococcus parasanguinis. Lactobacillus salivarius was the most discriminating species in the pSS patients, especially in those with interstitial lung disease (ILD). Among the differentiating microbial pathways, the superpathway of l-phenylalanine biosynthesis was also further enriched in pSS complicated with ILD. There were more virulence genes carried by the gut microbiota in pSS patients, most of which encoded peritrichous flagella, fimbriae, or curli fimbriae, three types of bacterial surface organelles involved in bacterial colonization and invasion. Five microbial peptides with the potential to mimic pSS-related autoepitopes were also enriched in the pSS gut. SLE and pSS shared significant gut microbial traits, including the community distribution, altered microbial taxonomy and pathways, and enriched virulence genes. However, Ruminococcus torques was depleted in pSS patients but enriched in SLE patients compared to that in healthy controls.

CONCLUSIONS

The gut microbiota in treatment naïve pSS patients was disturbed and shared significant similarity with that in SLE patients.

摘要

目的

研究原发性干燥综合征(pSS)患者肠道微生物群的组成和功能特征,并与系统性红斑狼疮(SLE)患者的进行比较。

方法

采用鸟枪法宏基因组测序检测78例未经治疗的pSS患者和78例匹配的健康对照的粪便样本,并与49例未经治疗的SLE患者的样本进行比较。还通过序列比对评估肠道微生物群的毒力负荷和模拟表位。

结果

未经治疗的pSS患者的肠道微生物群丰富度和均匀度较低,且群落分布与健康对照不同。pSS相关肠道微生物群中富集的微生物种类包括唾液乳杆菌、脆弱拟杆菌、纤细瘤胃球菌、巴氏梭菌、博氏梭菌、小韦荣球菌和副血链球菌。唾液乳杆菌是pSS患者中最具鉴别性的物种,尤其是在合并间质性肺病(ILD)的患者中。在差异微生物途径中,L-苯丙氨酸生物合成的超级途径在合并ILD的pSS中也进一步富集。pSS患者肠道微生物群携带的毒力基因更多,其中大多数编码周生鞭毛、菌毛或卷曲菌毛,这三种细菌表面细胞器参与细菌定植和侵袭。pSS肠道中还富集了五种具有模拟pSS相关自身表位潜力的微生物肽。SLE和pSS具有显著的肠道微生物特征,包括群落分布、微生物分类和途径改变以及毒力基因富集。然而,与健康对照相比,扭链瘤胃球菌在pSS患者中减少,而在SLE患者中富集。

结论

未经治疗的pSS患者的肠道微生物群受到干扰,与SLE患者的肠道微生物群有显著相似性。

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