HLA-A alleles including HLA-A29 affect the composition of the gut microbiome: a potential clue to the pathogenesis of birdshot retinochoroidopathy.
HLA-A alleles including HLA-A29 affect the composition of the gut microbiome: a potential clue to the pathogenesis of birdshot retinochoroidopathy.
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DOI：
10.1038/s41598-020-74751-0
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发表时间：
2020-10-19
影响因子：
4.6
通讯作者：
Rosenbaum JT
中科院分区：
文献类型：
--
作者：
Sternes PR;Martin TM;Paley M;Diamond S;Asquith MJ;Brown MA;Rosenbaum JT
鸟枪样视网膜脉络膜病变只发生在HLA-A29阳性的个体中。解释这种关联的机制尚不清楚。肠道微生物组与许多免疫介导的疾病有因果关系。我们假设HLA-A29会影响肠道微生物组的组成，导致生态失调和免疫介导的眼病。粪便和肠活检样品来自波特兰，俄勒冈州周围的107名健康个体，其中10人HLA-A 29阳性，接受常规结肠镜检查。细菌谱通过16 S rRNA元巴编码实现。还询问了来自人类微生物组计划（HMP）的公开可用的全元基因组测序数据，包括298名健康对照，大多数来自美国。PERMANOVA和稀疏偏最小二乘判别分析（sPLSDA）表明，在波特兰（p = 0.019）和HMP队列（p = 0.0002）中，与HLA-A29阴性受试者相比，HLA-A29阳性受试者的细菌种类组成（β多样性）不同。波特兰和HMP队列证明了与HLA-A29状态相关的细菌物种的不同子集，这可能是由于所采用的宏基因组技术的差异。HMP组群的功能组成在HLA-A29阳性和阴性受试者之间总体上没有差异（p = 0.14），尽管一些不同的途径如硫酸乙酰肝素生物合成显示出差异。正如我们和其他人已经证明的各种HLA等位基因，HLA同种异型影响微生物组的组成。我们假设HLA-A29可能通过改变肠道微生物组而易患脉络膜视网膜炎。
Birdshot retinochoroidopathy occurs exclusively in individuals who are HLA-A29 positive. The mechanism to account for this association is unknown. The gut microbiome has been causally implicated in many immune-mediated diseases. We hypothesized that HLA-A29 would affect the composition of the gut microbiome, leading to a dysbiosis and immune-mediated eye disease. Fecal and intestinal biopsy samples were obtained from 107 healthy individuals from Portland, Oregon environs, 10 of whom were HLA-A29 positive, undergoing routine colonoscopy. Bacterial profiling was achieved via 16S rRNA metabarcoding. Publicly available whole meta-genome sequencing data from the Human Microbiome Project (HMP), consisting of 298 healthy controls mostly of US origin, were also interrogated. PERMANOVA and sparse partial least squares discriminant analysis (sPLSDA) demonstrated that subjects who were HLA-A29 positive differed in bacterial species composition (beta diversity) compared to HLA-A29 negative subjects in both the Portland (p = 0.019) and HMP cohorts (p = 0.0002). The Portland and HMP cohorts evidenced different subsets of bacterial species associated with HLA-A29 status, likely due to differences in the metagenomic techniques employed. The functional composition of the HMP cohort did not differ overall (p = 0.14) between HLA-A29 positive and negative subjects, although some distinct pathways such as heparan sulfate biosynthesis showed differences. As we and others have shown for various HLA alleles, the HLA allotype impacts the composition of the microbiome. We hypothesize that HLA-A29 may predispose chorioretinitis via an altered gut microbiome.
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