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. 2024 May 7;21(1):120.
doi: 10.1186/s12974-024-03109-4.

The gut microbiome and HLA-B27-associated anterior uveitis: a case-control study

Sophia C Morandi  1   2 , Elio L Herzog  3   4 , Marion Munk  3 , Marco Kreuzer  5   6 , Carlo R Largiadèr  7 , Sebastian Wolf  3   5 , Martin Zinkernagel  3   5 , Denise C Zysset-Burri  3   5
Affiliations

The gut microbiome and HLA-B27-associated anterior uveitis: a case-control study

Sophia C Morandi et al. J Neuroinflammation. .

Abstract

Background: The human gut microbiome (GM) is involved in inflammation and immune response regulation. Dysbiosis, an imbalance in this ecosystem, facilitates pathogenic invasion, disrupts immune equilibrium, and potentially triggers diseases including various human leucocyte antigen (HLA)-B27-associated autoinflammatory and autoimmune diseases such as inflammatory bowel disease (IBD) and spondyloarthropathy (SpA). This study assesses compositional and functional alterations of the GM in patients with HLA-B27-associated non-infectious anterior uveitis (AU) compared to healthy controls.

Methods: The gut metagenomes of 20 patients with HLA-B27-associated non-infectious AU, 21 age- and sex-matched HLA-B27-negative controls, and 6 HLA-B27-positive healthy controls without a history of AU were sequenced using the Illumina NovaSeq 6000 platform for whole metagenome shotgun sequencing. To identify taxonomic and functional features with significantly different relative abundances between groups and to identify associations with clinical metadata, the multivariate association by linear models (MaAsLin) R package was applied.

Results: Significantly higher levels of the Eubacterium ramulus species were found in HLA-B27-negative controls (p = 0.0085, Mann-Whitney U-test). No significant differences in microbial composition were observed at all other taxonomic levels. Functionally, the lipid IVA biosynthesis pathway was upregulated in patients (p < 0.0001, Mann-Whitney U-test). A subgroup analysis comparing patients with an active non-infectious AU to their age- and sex-matched HLA-B27-negative controls, showed an increase of the species Phocaeicola vulgatus in active AU (p = 0.0530, Mann-Whitney U-test). An additional analysis comparing AU patients to age- and sex-matched HLA-B27-positive controls, showed an increase of the species Bacteroides caccae in controls (p = 0.0022, Mann-Whitney U-test).

Conclusion: In our cohort, non-infectious AU development is associated with compositional and functional alterations of the GM. Further research is needed to assess the causality of these associations, offering potentially novel therapeutic strategies.

Keywords: Bacteroides caccae; Eubacterium ramulus; Phocaeicola vulgatus; Anterior uveitis; Gut microbiome; HLA-B27; Lipid IVA biosynthesis; Whole metagenome shotgun sequencing.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Taxonomic characterization of the GM composition of the study group. Relative abundances of all phyla in HLA-B27- associated non-infectious AU patients (n = 20) and HLA-B27-negative controls (n = 21) (a), averaged for study groups (b)
Fig. 2
Fig. 2
Differences in microbial composition between patients and controls at species level. Comparisons between patients with HLA-B27-associated non-infectious AU and HLA-B27-negative controls (a). Subgroup analysis comparing patients with an HLA-B27-associated active AU at the time of sampling to controls (b). Dot plots show the relative abundance, mean, and SD of the species that were different between patients and controls. In the group analysis, Eubacterium ramulus was significantly increased in controls, while in the subgroup analysis Phocaeicola vulgatus was increased in patients with active AU
Fig. 3
Fig. 3
Differences in pathway expression between patients and controls. Comparisons between patients with HLA-B27-associated non-infectious AU and HLA-B27-negative controls (a). Subgroup analysis comparing patients with an active AU at the time of sampling to HLA-B27-negative controls (b). Dot plots show the relative abundance, mean and SD of the pathways significantly different between patients and controls. Lipid IVA biosynthesis was upregulated in patients in both, group and subgroup analysis
Fig. 4
Fig. 4
Differences in microbial composition between patients and HLA-B27-positive controls at species level. Comparisons between patients with HLA-B27-associated non-infectious AU and HLA-B27-positive controls. Dot plots show the relative abundance, mean, and SD of the species that were different between patients and controls. Bacteroides caccae was significantly increased in controls
Fig. 5
Fig. 5
Enterotype categorization of the study groups at genera level. BCA showed four enterotype clusters in the study groups. Patients (n = 20) are marked by triangles (∆) and controls (n = 21) by squares (□) (a). Calinski-Harabasz (CH) index was used to calculate the optimal number of clusters (b). Dot plots show the relative abundance, mean, and SD of the three genera identified to characterize the four enterotypes (c). The colors for the four enterotypes are blue for 1, red for 2, green for 3, and orange for 4
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References

    1. Durrani OM, Tehrani NN, Marr JE, Moradi P, Stavrou P, Murray PI. Degree, duration, and causes of visual loss in uveitis. Br J Ophthalmol. 2004;88(9):1159–62. doi: 10.1136/bjo.2003.037226. - DOI - PMC - PubMed
    1. Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005;140(3):509–16. - PMC - PubMed
    1. Joltikov KA, Lobo-Chan AM. Epidemiology and risk factors in non-infectious Uveitis: a systematic review. Front Med (Lausanne) 2021;8:695904. doi: 10.3389/fmed.2021.695904. - DOI - PMC - PubMed
    1. Forrester JV, Kuffova L, Dick AD. Autoimmunity, autoinflammation, and infection in Uveitis. Am J Ophthalmol. 2018;189:77–85. doi: 10.1016/j.ajo.2018.02.019. - DOI - PubMed
    1. Willermain F, Rosenbaum JT, Bodaghi B, Rosenzweig HL, Childers S, Behrend T, et al. Interplay between innate and adaptive immunity in the development of non-infectious uveitis. Prog Retin Eye Res. 2012;31(2):182–94. doi: 10.1016/j.preteyeres.2011.11.004. - DOI - PMC - PubMed

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