Abstract
ObjectiveTo investigate gut dysbiosis in patients with Sjögren’s syndrome (SS) or dry eye syndrome (DES) compared to normal subjects and to evaluate the association of dysbiosis with dry eye severity.Methods10 subjects with SS, 14 subjects with DES and 12 controls were enrolled. Corneal staining, tear break up time (TBUT) and tear secretion were evaluated. Bacterial genomic 16s rRNA from stool samples were analyzed. Main outcomes were microbiome compositional differences among groups and their correlation to dry eye signs.ResultsGut microbiome analysis revealed significant compositional differences in SS compared to controls and DES. In phylum, Bacteriodetes increased, while Firmicutes/Bacteroidetes ratio and Actinobacteria decreased (p<0.05). In genus, Bifidobacterium was reduced (vs controls; p = 0.025, vs DES; p = 0.026). Beta diversity of SS also showed significant distances from controls and DES (p = 0.007 and 0.019, respectively). SS showed decreased genus of Blautia (p = 0.041), Dorea (p = 0.025) and Agathobacter (p = 0.035) compared to controls and increased genus of Prevotella (p = 0.026), Odoribacter (p = 0.028) and Alistipes (p = 0.46) compared to DES. On the other hand, DES only had increased genus Veillonella (p = 0.045) and reduced Subdoligranulum (p = 0.035) compared to controls. Bacteroidetes, Actinobacteria and Bifidobacterium were significantly related with dry eye signs (p<0.05). After adjustment of age, gender and group classification, multivariate linear regression analysis revealed tear secretion was strongly affected by Prevotella (p = 0.025). With additional adjustment of hydroxychloroquine use, TBUT was markedly affected by Prevotella (p = 0.037) and Actinobacteria (p = 0.001).ConclusionsSjögren’s syndrome showed significant gut dysbiosis compared to controls and environmental dry eye syndrome, while dry eye patients showed compositional changes of gut microbiome somewhere in between Sjögren’s syndrome and controls. Dysbiosis of the gut microbiota was partly correlated to dry eye severity.
Highlights
Sjogren’s syndrome (SS) is one of the most common chronic autoimmune diseases and is associated with lymphocytic infiltration in exocrine glands and various other organs
Dysbiosis of the gut microbiota was partly correlated to dry eye severity
Intestinal epithelial cells are reported to play an essential role in balancing gut microbiota and their metabolic changes can result in dysbiosis in certain autoimmune diseases[10, 17]
Summary
Sjogren’s syndrome (SS) is one of the most common chronic autoimmune diseases and is associated with lymphocytic infiltration in exocrine glands and various other organs. Its symptoms include dry mouth, musculoskeletal pain and dry eyes[1, 2]. Among these symptoms, dry eye is one of the most discomforting symptoms that SS patients complain about and SS-related dry eye treatment is challenging compared to environmental dry eye syndrome (DES)[3, 4]. Intestinal epithelial cells are reported to play an essential role in balancing gut microbiota and their metabolic changes can result in dysbiosis in certain autoimmune diseases[10, 17]. The gut microbiota has been reported to be interactive in maintaining balance in immune responses between regulatory T cells (Tregs) and T helper 17 (Th17) cells at mucosal surface and to act as a trigger of inducing autoimmunity, such as SLE, rheumatic diseases or SS[9, 18]
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