The microbiome in Sjögren's syndrome: A missing link for ocular microbiome in autoimmune dry eye

Sjögren's syndrome (SS) is a systemic autoimmune disorder frequently associated with aqueous-deficient dry eye, driven by lacrimal gland dysfunction and chronic ocular surface inflammation. While immune dysregulation remains central to disease pathogenesis, emerging evidence may suggest that microbial communities at the ocular surface and along the gut-eye-lacrimal axis may contribute to ocular immune homeostasis and inflammatory disease expression. This review summarizes the composition and immunological functions of the healthy ocular surface microbiota and critically discusses available data on microbial alterations in SS-associated dry eye. Current human studies describe changes in ocular surface microbial diversity and composition, including shifts in commensal and potentially inflammation-associated taxa; however, these findings remain largely associative and are influenced by the low-biomass nature of ocular samples and methodological variability. Experimental evidence supporting a causal role for microbiota in ocular immune regulation derives mainly from murine models of gut microbiota manipulation or transfer, rather than from direct demonstration of causality for the ocular microbiome in human SS. These models may sugges that gut microbial communities may influence ocular surface barrier integrity, cytokine responses, and T-cell polarization, including the Th17/Treg balance. We also discuss microbial-derived metabolites, including short-chain fatty acids and indole derivatives, and their potential relevance to mucosal immune regulation. Overall, the ocular and gut-associated microbiome may represent an important interface between mucosal immunity and autoimmune dry eye in SS, but further studies are required before a causal role for the ocular microbiome itself can be established.