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. 2014 Aug 20;9(8):e105684.
doi: 10.1371/journal.pone.0105684. eCollection 2014.

HLA-B27 and human β2-microglobulin affect the gut microbiota of transgenic rats

Phoebe Lin  1 , Mary Bach  2 , Mark Asquith  3 , Aaron Y Lee  4 , Lakshmi Akileswaran  5 , Patrick Stauffer  1 , Sean Davin  1 , Yuzhen Pan  1 , Eric D Cambronne  6 , Martha Dorris  7 , Justine W Debelius  8 , Christian L Lauber  8 , Gail Ackermann  8 , Yoshiki V Baeza  8 , Tejpal Gill  9 , Rob Knight  10 , Robert A Colbert  9 , Joel D Taurog  7 , Russell N Van Gelder  5 , James T Rosenbaum  11
Affiliations

HLA-B27 and human β2-microglobulin affect the gut microbiota of transgenic rats

Phoebe Lin et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. 16S rRNA gene sequencing principal coordinates analysis from non-co-housed rats shows significant differences in cecal microbiota between genotypes.
A. Cecal lumen samples from cohort 3; B, Cecal mucosa samples from cohort 3; C, Phylum-level analysis from cecum lumen samples; D, Phylum-level analysis from cecum mucosa samples. WT: wild type rats; B2M: hβ2 microglobulin; B27/B2M: HLA-B27/hβ2 microglobulin transgenic rats.
Figure 2
Figure 2. Genus level analysis differences from A, cecal lumen specimens, and B, cecal mucosal samples from cohort 3.
Figure 3
Figure 3. Principal coordinates analysis from combined cecal lumen and cecal mucosa samples from cohort 3.
Figure 4
Figure 4. BRISK analysis of whole cecum samples from cohort 1 shows microbial diversity differences on a species level between HLA-B27/hβ2m animals and co-housed wild type animals.
A. Each line on the heat map represents a different bacterial species and the color code represents the relative abundance of that organism, with yellow indicating the highest abundance. B, Specific species differences are highlighted, with a black dot indicating statistically significant differences.
Figure 5
Figure 5. Relative differences in Bacteroides vulgatus and Akkermansia muciniphila shown by A, quantitative PCR using the 16S rRNA gene as a reference, and B, by traditional PCR using whole cecum samples in cohort 1.
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