Abstract
The aims of this study were to explore intestinal microbial composition and functionality in primary Sjögren’s syndrome (pSS) and to relate these findings to inflammation, permeability and the transcription factor Forkhead box protein P3 (FOXP3) gene expression in peripheral blood. The study included 19 pSS patients and 19 healthy controls matched for age, sex, and body mass index. Fecal bacterial DNA was extracted and analyzed by 16S rRNA sequencing using an Ion S5 platform followed by a bioinformatics analysis using Quantitative Insights into Microbial Ecology (QIIME II) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Our data suggest that the gut microbiota of pSS patients differs at both the taxonomic and functional levels with respect to healthy controls. The gut microbiota profile of our pSS patients was characterized by a lower diversity and richness and with Bacteroidetes dominating at the phylum level. The pSS patients had less beneficial or commensal butyrate-producing bacteria and a higher proportion of opportunistic pathogens with proinflammatory activity, which may impair intestinal barrier function and therefore contribute to inflammatory processes associated with pSS by increasing the production of proinflammatory cytokines and decreasing the release of the anti-inflammatory cytokine IL-10 and the peripheral FOXP3 mRNA expression, implicated in the development and function of regulatory T cells (Treg) cells. Further studies are needed to better understand the real impact of dysbiosis on the course of pSS and to conceive preventive or therapeutic strategies to counteract microbiome-driven inflammation.
Highlights
Primary Sjögren’s syndrome is a systemic inflammatory autoimmune disease characterized by chronic inflammation of the exocrine glands, in particular the salivary and lacrimal glands, resulting in oral and ocular dryness complaints [1]
We found a significant rise in Bacteroidetes (40.24% Primary Sjögren’s syndrome (pSS) vs. 33.05% HC, p < 0.001, q-value < 0.001) and Proteobacteria (11.22% pSS vs. 6.98% HC, p = 0.0020, q-value = 0.017) in pSS patients compared to healthy controls
This study has demonstrated that the pSS patients had gut dysbiosis associated with increased serum levels of proinflammatory cytokines including IL-6, IL-12, IL-17 and tumor necrosis factor (TNF)-alpha and zonulin that resulted in increased systemic microbial exposure
Summary
Primary Sjögren’s syndrome (pSS) is a systemic inflammatory autoimmune disease characterized by chronic inflammation of the exocrine glands, in particular the salivary and lacrimal glands, resulting in oral and ocular dryness (sicca) complaints [1]. Several recent studies have described differences in the gut and oral microbiota of pSS patients compared with healthy and symptom controls. High levels of Lactobacillus spp. were found in supragingival plaque samples [7]. Concerning gut microbiota, these authors observed depletion of Faecalibacterium, Bacteroides, Parabacteroides and Prevotella and enhancement of Escherichia, Shigella, and Streptococcus genera [7]. Mandl et al found that severe intestinal dysbiosis was more prevalent in pSS patients in comparison to healthy controls and this dysbiosis was associated with clinical and laboratory markers of systemic disease activity and with gastrointestinal inflammation [8]
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