Role of the Microbiome and Its Metabolites in Primary Sjögren's Syndrome

Primary Sjögren's syndrome (pSS) is a chronic, autoimmune rheumatic disease characterized by progressive lymphocytic infiltration of the exocrine glands, leading to inflammation and subsequent tissue damage. As a multifactorial disease, its etiology is complex, making it difficult to predict disease progression. Among the environmental factors implicated in pSS, the involvement of microorganisms has gained increasing attention. Since the launch of the Human Microbiome Project, growing evidence has highlighted the role of dysbiosis in the pathogenesis of various autoimmune diseases, including pSS. Shifts in the abundance of specific bacterial phyla can lead to corresponding changes in the levels of key microbial metabolites involved in tissue homeostasis and immune regulation-such as short-chain fatty acids (SCFAs), choline, taurine, serine, lactate, and tryptophan and their metabolites. Understanding the mechanisms by which these metabolites influence immune processes may provide deeper insights into the progression of the disease. Therefore, this review aims to explore the mechanisms through which microbiota-derived metabolites contribute to the pathophysiology of primary Sjögren's syndrome.