Gut dysbiosis is prevailing in Sjögren’s syndrome and is related to dry eye severity

Abstract

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).

The Gut–Eye Axis: Lessons Learned from Murine Models

“…Sjögren's syndrome (SS) is an autoimmune condition characterized by lymphocytic infiltration in exocrine glands, particularly the lacrimal glands, causing dry eyes [82,83]. Moon et al recently published a study in which changes in the gut microbiota were found to be associated with SS in human subjects compared to healthy volunteers and subjects with environmental dry eye syndrome (DES) [82].…”

“…Sjögren's syndrome (SS) is an autoimmune condition characterized by lymphocytic infiltration in exocrine glands, particularly the lacrimal glands, causing dry eyes [82,83]. Moon et al recently published a study in which changes in the gut microbiota were found to be associated with SS in human subjects compared to healthy volunteers and subjects with environmental dry eye syndrome (DES) [82]. SS was associated with a decreased F/B ratio, decreased Actinobacteria, and decreased abundance of members of the Bifidobacterium, Blautia, Dorea, and Agathobacter genera, with increased abundance of members of the Prevotella, Odoribacter, and Alistipes genera [82].…”

“…Moon et al recently published a study in which changes in the gut microbiota were found to be associated with SS in human subjects compared to healthy volunteers and subjects with environmental dry eye syndrome (DES) [82]. SS was associated with a decreased F/B ratio, decreased Actinobacteria, and decreased abundance of members of the Bifidobacterium, Blautia, Dorea, and Agathobacter genera, with increased abundance of members of the Prevotella, Odoribacter, and Alistipes genera [82]. Furthermore, severe dysbiosis, as assessed by the Dysbiosis Index score (DIS), was prevalent in subjects with primary SS (pSS).…”

Association of a dysbiotic oral microbiota with the development of focal lymphocytic sialadenitis in IκB-ζ-deficient mice

“…Another limitation of the current study is the lack of information on the gut microbiota. Gut microbial dysbiosis has also been reported in SS patients particularly in association with dry eyes 12 , 36 . There is a possibility that the gut microbiota contributed to the development and mitigation of FLS in the noncohoused and cohoused Nfkbiz −/− mice, respectively, through regulation of the common mucosal immune system.…”

Current insights into the relationship between the gut microbiome and Sjögren’s syndrome

“…Several studies analyzed the gut microbiome in pSS patients [6][7][8][9][10], but for some reason Mendez et al limited the comparison of their data only to the study by de Paiva et al [7]. Mendez et al stated that a similar decrease in relative abundance of Faecalibacterium and Bacteroides was found in both studies [1,7].…”