Abstract
There is mounting evidence that the microbiome has potent immunoregulatory functions. We assessed the effects of intestinal dysbiosis in a model of Sjögren syndrome (SS) by subjecting mice to desiccating stress (DS) and antibiotics (ABX). We characterized the conjunctival, tongue and fecal microbiome profiles of patients with SS. Severity of ocular surface and systemic disease was graded. 16S ribosomal RNA gene sequencing characterized the microbiota. ABX + DS mice had a significantly worse dry eye phenotype compared to controls, a decrease in Clostridium and an increase in Enterobacter, Escherichia/Shigella, and Pseudomonas in stool after ABX + DS for 10 days. Goblet cell density was significantly lower in ABX treated groups compared to controls. Stool from SS subjects had greater relative abundances of Pseudobutyrivibrio, Escherichia/Shigella, Blautia, and Streptococcus, while relative abundance of Bacteroides, Parabacteroides, Faecalibacterium, and Prevotella was reduced compared to controls. The severity of SS ocular and systemic disease was inversely correlated with microbial diversity. These findings suggest that SS is marked by a dysbiotic intestinal microbiome driven by low relative abundance of commensal bacteria and high relative abundance of potentially pathogenic genera that is associated with worse ocular mucosal disease in a mouse model of SS and in SS patients.
Highlights
Sjögren syndrome (SS) is one of the most common mucosal autoimmune diseases with a reported prevalence of 0.09–2.7% depending on the diagnostic criteria used[1]
We evaluated the effects of antibiotic (ABX) treatment on severity of ocular disease in a validated mouse dry eye model with features of SS
Members of the Bacteroidetes and Firmicutes phyla dominate the intestinal microbiome, and the microbiome of an individual is more similar to self over time than to others[48]
Summary
Sjögren syndrome (SS) is one of the most common mucosal autoimmune diseases with a reported prevalence of 0.09–2.7% depending on the diagnostic criteria used[1]. SS primarily affects the secretory glands and mucosal tissues of the eye and mouth Both the lacrimal and salivary glands become infiltrated with activated CD4+ T cells and B cells[2,3]. Ocular surface and oral mucosal disease develops from reduced lubrication, as well as from cytokines produced by activated epithelial cells and infiltrating inflammatory cells[4,5,6]. IL-17 promotes lymphangiogenesis and stimulates production of matrix metalloproteinases (MMPs) that accelerate desquamation of apical epithelial cells leading to corneal barrier disruption[15,16] The factors inciting this immune based mucosal inflammation are not fully understood[17]. Not all individuals with these genetic risk factors develop disease, and the prevalence of this condition in siblings of patients with SS is no higher than the population in general[21]. Frequent antibiotic use during the first year of life was found to increase the risk of developing Crohn’s disease[26], and increased adherent-invasive Escherichia coli or decreased Faecalibacterium prausnitzii, a major intestinal butyrate produce, have been associated with disease activity[27]
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