Gut Dysbiosis in Ocular Mucous Membrane Pemphigoid

Abstract

Mucous Membrane Pemphigoid is an orphan multi-system autoimmune scarring disease involving mucosal sites, including the ocular surface (OcMMP) and gut. Loss of tolerance to epithelial basement membrane proteins and generation of autoreactive T cell and/or autoantibodies are central to the disease process. The gut microbiome plays a critical role in the development of the immune system. Alteration in the gut microbiome (gut dysbiosis) affects the generation of autoreactive T cells and B cell autoantibody repertoire in several autoimmune conditions. This study examines the relationship between gut microbiome diversity and ocular inflammation in patients with OcMMP by comparing OcMMP gut microbiome profiles with healthy controls. DNA was extracted from faecal samples (49 OcMMP patients, 40 healthy controls), amplified for the V4 region of the 16S rRNA gene and sequenced using Illumina Miseq platform. Sequencing reads were processed using the bioinformatics pipeline available in the mothur v.1.44.1 software. After adjusting for participant factors in the multivariable model (age, gender, BMI, diet, proton pump inhibitor use), OcMMP cohort was found to be associated with lower number of operational taxonomic units (OTUs) and Shannon Diversity Index when compared to healthy controls. Within the OcMMP cohort, the number of OTUs were found to be significantly correlated with both the bulbar conjunctival inflammation score (p=0.03) and the current use of systemic immunotherapy (p=0.02). The linear discriminant analysis effect size scores indicated that Streptococcus and Lachnoclostridium were enriched in OcMMP patients whilst Oxalobacter, Clostridia uncultured genus-level group (UCG) 014, Christensenellaceae R-7 group and butyrate-producing bacteria such as Ruminococcus, Lachnospiraceae, Coprococcus, Roseburia, Oscillospiraceae UCG 003, 005, NK4A214 group were enriched in healthy controls (Log10 LDA score < 2, FDR-adjusted p <0.05). In conclusion, OcMMP patients have gut dysbiosis correlating with bulbar conjunctival inflammation and the use of systemic immunotherapies. This provides a framework for future longitudinal deep phenotyping studies on the role of the gut microbiome in the pathogenesis of OcMMP.

Diagnosis and functional prediction of microbial markers in tumor tissues of sporadic colorectal cancer patients associated with the MLH1 protein phenotype

“…Previous studies have reported that some butyrate-producing bacteria of Coprococcus spp. ( Firmicutes ) could stimulate aberrant hyperproliferation of colonic epithelial cells with MSH2 or MLH1 deficiency and enhance β-catenin activity by increasing butyrate levels ( 50 – 52 ). Dronamraju et al.…”

Identification of gut microbiota dysbiosis in bullous pemphigoid under different disease activity

“…In previous study, other autoimmune bullous diseases such as mucous membrane pemphigoid (MMP) have been investigated and GM dysbiosis was observed in MMP patients. 14 In BP patients, the skin microbiota composition has been proven to be substantially different from the healthy people and a novel indicator of disease. 15 The GM in BP patients has rarely been examined.…”

“…16 Immunosuppressive agents can change the composition of GM and reduce the diversity, leading to an imbalance of GM and further aggravating the disease in MMP patients. 14 Although these studies identified that changes in the GM were associated with treatment, little is known about the variations during BP treatment. Investigation into the different stages of BP may help us understand the mechanism of treatment better.…”

“…Studies have shown that GM is related to the pathogenesis of autoimmune diseases, 12 through interacting with the immune system leading to inflammation and loss of immune tolerance 13 or affecting the production of autoreactive T helper cells. In previous study, other autoimmune bullous diseases such as mucous membrane pemphigoid (MMP) have been investigated and GM dysbiosis was observed in MMP patients 14 . In BP patients, the skin microbiota composition has been proven to be substantially different from the healthy people and a novel indicator of disease 15 .…”

“…In systemic lupus erythematosus (SLE) patients, the diversity and structure of the microbial community were significantly changed after undergoing corticosteroids treatment, and the gut microbial community after treatment showed a similarity with the healthy controls (HC), which implicate that the shift in the GM could represent a return to homeostasis 16 . Immunosuppressive agents can change the composition of GM and reduce the diversity, leading to an imbalance of GM and further aggravating the disease in MMP patients 14 . Although these studies identified that changes in the GM were associated with treatment, little is known about the variations during BP treatment.…”