Objective To investigate gut dysbiosis in patients with Sjö gren's syndrome (SS) or dry eye syndrome (DES) compared to normal subjects and to evaluate the association of dysbiosis with dry eye severity. Methods 10 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. Results Gut 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).