Altered Mucosal Microbiome Diversity and Disease Severity in Sjögren Syndrome

TLDR

The microbiome is increasingly recognized for its potent immunoregulatory roles. The study aimed to evaluate how intestinal dysbiosis influences Sjögren syndrome by exposing mice to desiccating stress and antibiotics. Researchers profiled conjunctival, tongue, and fecal microbiomes of SS patients and mice using 16S rRNA sequencing and graded ocular and systemic disease severity. ABX‑treated mice displayed a worsened dry‑eye phenotype, reduced goblet cells, and shifts toward pathogenic bacteria, while SS patients showed decreased commensal and increased potentially harmful genera, with disease severity inversely related to microbial diversity, indicating that dysbiosis drives ocular mucosal disease.

Abstract

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.