Gut microbial signatures and their functions in Behcet's uveitis and Vogt-Koyanagi-Harada disease

作者全名："Wang, Qingfeng; Wu, Shuang; Ye, Xingsheng; Tan, Shiyao; Huang, Fanfan; Su, Guannan; Kijlstra, Aize; Yang, Peizeng"

作者地址："[Wang, Qingfeng; Ye, Xingsheng; Tan, Shiyao; Huang, Fanfan; Su, Guannan; Yang, Peizeng] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Ophthalmol, Chongqing Eye Inst,Chongqing Branch,Municipal Div, Chongqing, Peoples R China; [Wu, Shuang] Guangxi Minzu Univ, Sch Marine Sci & Biotechnol, Guangxi Key Lab Polysaccharide Mat & Modificat, Nanning, Peoples R China; [Kijlstra, Aize] Univ Eye Clin Maastricht, Maastricht, Netherlands; [Yang, Peizeng] Chongqing Med Univ, Affiliated Hosp 1, Youyi Rd 1, Chongqing 400016, Peoples R China"

通信作者："Yang, PZ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Youyi Rd 1, Chongqing 400016, Peoples R China."

来源：JOURNAL OF AUTOIMMUNITY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001024836500001

JCR分区：Q1

影响因子：7.9

年份：2023

卷号：137

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Gut microbiome; Behcet 's uveitis (BU); Vogt-Koyanagi-Harada disease (VKH); Metagenomic sequencing; Immune-mediated disease

摘要："Background: A number of public metagenomic studies reveal an association between the gut microbiome and various immune-mediated diseases including Behcet's uveitis (BU) and Vogt-Koyanagi-Harada disease (VKH). Integrated-analysis and subsequent validation of these results could be a potentially powerful way to understand the microbial signatures and their functions in these two uveitis entities. Methods: We integrated the sequencing data of our previous metagenomic studies on two major uveitis entities, BU and VKH as well as four other publicly available immune-mediated diseases datasets, including Ankylosing Spondylitis (AS), Rheumatoid Arthritis (RA), Crohn's disease (CD) and Ulcerative Colitis (UC). Alpha-diversity and beta-diversity analysis were used to compare the gut microbiome signatures between both uveitis entities and other immune-mediated diseases and healthy controls. Amino acid homology between microbial proteins and a uveitogenic peptide of the interphotoreceptor retinoid-binding protein (IRBP)161-180 was investigated using a similarity search in the NCBI protein BLAST program (BLASTP). Enzyme-linked Immunosorbent Assay (ELISA) was performed to evaluate the cross-reactive responses of experimental autoimmune uveitis (EAU)-derived lymphocytes and BU patients-derived peripheral blood mononuclear cells (PBMCs) against homologous peptides. The area under the curve (AUC) analysis was used to test the sensitivity and specificity of gut microbial biomarkers. Results: Depleted Dorea, Blautia, Coprococcus, Erysipelotrichaceae and Lachnospiraceae as well as enriched Bilophila and Stenotrophomonas were identified in BU patients. An enriched Alistipes along with a lower level of Dorea were observed in VKH patients. A peptide antigen (SteTDR) encoded by BU specifically enriched Stenotrophomonas was identified to share homology with IRBP161-180. In vitro experiments showed that lymphocytes from EAU or PBMCs from BU patients reacted to this peptide antigen as shown by the production of IFN-& gamma; and IL17. Addition of the SteTDR peptide to the classical IRBP immunization protocol exacerbated EAU severity. Gut microbial marker profiles consisted of 24 species and 32 species respectively differentiated BU and VKH from each other as well as from the other four immune-mediated diseases and healthy controls. Protein annotation identified 148 and 119 specific microbial proteins associated with BU and VKH, respectively. For metabolic function analysis, 108 and 178 metabolic pathways were shown to be associated with BU and VKH, respectively. Conclusions: Our study revealed specific gut microbial signatures and their potentially functional roles in BU and VKH pathogenesis that differ significantly from other immune-mediated diseases as well as healthy controls."

基金机构：National Natural Science Foundation Key Program [81930023]; National Natural Science Foundation [CSTC2021jscx-gksb-N0010]; Natural Science Key Project of Chongqing Science and Technology Bureau [cstc2021jcyj-bsh0055]; Foundation of Chongqing [2008CA5003]; Chongqing Outstanding Scientists Project (2019); Chongqing Chief Medical Scientist Project (2018); Chongqing Key Laboratory of Ophthalmology (CSTC) [cstc2014pt-sy10002]; Chongqing Science amp; Technology Platform [82230032]; [82101106]

基金资助正文："This study was supported by the National Natural Science Foundation Key Program (81930023) , National Natural Science Foundation Key Program (82230032) , National Natural Science Foundation (82101106) , Natural Science Key Project of Chongqing Science and Technology Bureau (CSTC2021jscx-gksb-N0010) , Foundation of Chongqing (cstc2021jcyj-bsh0055) , Chongqing Outstanding Scientists Project (2019) , Chongqing Chief Medical Scientist Project (2018) , Chongqing Key Laboratory of Ophthalmology (CSTC, 2008CA5003) and Chongqing Science & amp; Technology Platform and Base Construction Pro- gram (cstc2014pt-sy10002) ."