HLA-B27 and Human β2-Microglobulin Affect the Gut Microbiota of Transgenic Rats

Abstract

The HLA-B27 gene is a major risk factor for clinical diseases including ankylosing spondylitis, acute anterior uveitis, reactive arthritis, and psoriatic arthritis, but its mechanism of risk enhancement is not completely understood. The gut microbiome has recently been shown to influence several HLA-linked diseases. However, the role of HLA-B27 in shaping the gut microbiome has not been previously investigated. In this study, we characterize the differences in the gut microbiota mediated by the presence of the HLA-B27 gene. We identified differences in the cecal microbiota of Lewis rats transgenic for HLA-B27 and human β2-microglobulin (hβ2m), compared with wild-type Lewis rats, using biome representational in situ karyotyping (BRISK) and 16S rRNA gene sequencing. 16S sequencing revealed significant differences between transgenic animals and wild type animals by principal coordinates analysis. Further analysis of the data set revealed an increase in Prevotella spp. and a decrease in Rikenellaceae relative abundance in the transgenic animals compared to the wild type animals. By BRISK analysis, species-specific differences included an increase in Bacteroides vulgatus abundance in HLA-B27/hβ2m and hβ2m compared to wild type rats. The finding that HLA-B27 is associated with altered cecal microbiota has not been shown before and can potentially provide a better understanding of the clinical diseases associated with this gene.

Is Behçet's disease a ‘class 1-opathy’? The role of HLA-B*51 in the pathogenesis of Behçet's disease

“…For example, in AS there is evidence of gut microbiome dysbiosis with an abundance of the genus Dialister correlated with disease activity [35]. Supporting this information, Lin et al [36] showed that the gut microbiota is different in HLA-B*27 transgenic mice compared with wild-type mice, showing a correlation between possession of HLA-B*27 and the shaping of the gut microbiome. In patients with skin psoriasis and PsA a recent study found that the diversity of the gut microbiome was lower compared to healthy controls, due to a lower abundance of several taxa [37].…”

New Possibilities of Pharmacotherapy for Immunoinflammatory Rheumatic Diseases: A Focus on Inhibitors of Interleukin-17

“…Другой важный аспект этой проблемы связан с ро-лью кишечного воспаления в патогенезе СпА [58][59][60]. По данным экспериментальных исследований, у «транс-генных» мышей, несущих гены HLA-B27 и β2-микрогло-булина, отмечается развитие воспаления кишечника, коррелирующее с увеличением экспрессии ИЛ12 и ИЛ17 в воспаленной ткани [61,62]. Установлено нарушение кишечной микробиоты у трансгенных HLA-B27 крыс по сравнению с диким типом [63].…”

Epigenetics and Axial Spondyloarthritis - DNA is not Destiny

“…Intestinal dysbiosis is now being understood as a major cause of dysregulated immunity in Ax SpA. Diversity in the intestinal microbiome may alter immunogenetic and epigenetic factors that confer risk for this disease [13,14].…”