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Liying Low, Kusy Suleiman, Mariam Murad, Kaki Tsang, Matthew Davidson, Kerolos Bassilious, Mohith Shamdas, Natraj Poonit, Amanda Rossiter, Philip Ian Murray, Graham R Wallace, Saaeha Rauz; Gut dysbiosis in Ocular Mucous Membrane Pemphigoid. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1220.
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© ARVO (1962-2015); The Authors (2016-present)
Mucous Membrane Pemphigoid is a multi-system autoimmune scarring disease involving mucosal sites, including the ocular surface (OcMMP) and gastrointestinal tract. Loss of tolerance to epithelial basement membrane proteins (BMP), and generation of autoreactive T cell and/or autoantibodies to BMP are central to the disease process. Mechanisms on how and where the T cells first become autoreactive is unknown.The gut microbiome plays a critical role in the development of the immune system and has been shown to activate ocular autoimmune T cells. The aims of this study were to 1) compare the gut microbiome profiles of OcMMP patients with age- and gender-matched controls, and to 2) examine the relationship between the gut microbiome diversity and ocular inflammation in OcMMP.
Faecal samples were collected from 50 OcMMP patients attending a tertiary referral centre and 40 healthy controls and DNA extracted, amplified for the V4 region of the 16S rRNA gene and sequenced using Illumina Miseq platform. Sequencing reads were processed using bioinformatics pipeline available in the mothur v.1.44.1 software.
OcMMP patients had lower alpha diversity compared to healthy controls (HC) [Median observed OTUs in OcMMP: 214 (IQR: 173 – 276) vs HC: 317 (277 – 549), p <0.0001; Median Shannon Index in OcMMP: 3.05 (2.54 – 3.45) vs HC: 3.60 (3.18 – 4.01), p <0.0001]. Reduced number of observed OTUs were correlated with conjunctival inflammation (R2: 0.1, p= 0.03). Alpha-diversity was not significantly associated with duration of disease, treatment, clinical scoring of scarring and morbidity, or immunofluorescence results. The linear discriminant analysis effect size scores indicated that Streptococcus, Lachnoclostridium, and Eggerthella were enriched in OcMMP patients whilst Oxalobacter, Clostridia, uncultured genus-level group (UCG) 014, Christensenellaceae R-7 group, UCG 002, 003, 005, NK4A214 group and butyrate-producing bacteria such as Ruminococcus, Lachnospiraceae, Oscillospiraceae, Coprococcus, Roseburia were enriched in healthy controls (Log10 LDA score < 2, FDR-adjusted p <0.05).
OcMMP patients have gut dysbiosis correlating with ocular inflammation, providing the framework for future causative studies on the role of the gut microbiome in OcMMP.
This is a 2021 ARVO Annual Meeting abstract.
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