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Phoebe Lin, Mary Bach, Aaron Lee, Lakshmi Akileswaran, Joel Taurog, James Rosenbaum, Russell Van Gelder; HLA-B27 affects the gut microbiome of transgenic rats. Invest. Ophthalmol. Vis. Sci. 2013;54(15):353. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The HLA-B27 gene is a major risk factor for acute anterior uveitis, but its mechanism of risk enhancement is not completely understood. The gut microbiome has been shown to be important in the development of HLA-B27-mediated arthritis in transgenic rats as demonstrated by abrogating clinical disease by rearing animals in a germ-free environment. However, the role of HLA-B27 in shaping the gut microbiome has not been elucidated. In this study, we characterize the differences in the gut microflora mediated by the presence of the HLA-B27 gene.
We identified differences between the cecal microbiome in 45 day-old co-transgenic HLA-B27/beta2-microglobulin Lewis rats (n=7) compared with wild-type Lewis rats (n=6 co-housed, n=3 non-co-housed) using biome representational in situ karyotyping (BRISK). Co-housed rats are housed in the same cages as their transgenic littermates, which is expected to minimize microbiome differences since rats are coprophagic. We confirmed differences by quantitative PCR (qPCR) with normalization based on amplification of 16S ribosomal DNA.
Of 909 species of bacteria identified by BRISK, 30 species showed statistically significant differences in HLA-B27/beta2microglobulin transgenic rats compared to wild-type controls as determined by iterative Monte Carlo analysis of the dataset. The three organisms showing the most difference were Faecalibacterium prausnitzii, Bacteroides vulgatus, and Akkermansia muciniphila. A difference in F. prausnitzii could not be confirmed by qPCR. However, there were higher levels of B. vulgatus and lower levels of Akkermansia in transgenic rats compared to non-co-housed control rats (Figure 1). Co-housed control rats did not demonstrate as large a difference in these two organisms compared to their transgenic cage mates. Both B.vulgatus and Akkermansia have been implicated in other immune-mediated diseases. Figure 1. Relative abundance of B. vulgatus and Akkermansia muciniphila from cecal flora of B27/beta2microglobulin rats compared to control rats. 16s rDNA served as amplification controls.
The presence of HLA-B27 alters the gut microflora by increasing B. vulgatus and decreasing Akkermansia. While a causal role cannot be proven, a protective effect of Akkermansia and a disease-producing effect of B. vulgatus are plausible.
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