SEARCHNARRATIVE_REVIEWophthalmology, rheumatology

narrative_review·ophthalmology, rheumatology, immunology, microbiome, dry eye·PMC10270702

Sjögren’s Syndrome Treatments in the Microbiome Era

Advances in geriatric medicine and research · 3 authors, 2 centres

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TL;DR

This review explores the role of gut, oral, and ocular microbiome dysbiosis in Sjögren’s syndrome (SS) and discusses emerging microbiome-based therapies. Preclinical and early clinical studies suggest that probiotics, fecal microbiota transplantation, and engineered bacteria can modulate immune responses and alleviate symptoms like dry eye and oral candidiasis. The findings highlight the potential of microbiome-targeted interventions as novel treatments for SS, though further clinical validation is needed.

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**Background:** Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by inflammatory infiltration of salivary and lacrimal glands, leading to dryness of the eyes and mouth, and affecting up to 3.1 million people in the U.S., with a female-to-male ratio of 9:1. Current treatments are limited to artificial tears, saliva substitutes, and immunosuppressants with partial efficacy. The gut microbiome is increasingly recognized as a key modulator of immune function, and dysbiosis has been linked to SS pathogenesis. This narrative review summarizes evidence on microbiome alterations in SS and explores therapeutic strategies including probiotics, fecal microbiota transplantation (FMT), and synthetic biology-engineered bacteria.

**Methods:** The authors conducted a narrative review of the literature, citing studies on microbiome composition in SS patients, animal models, and clinical trials of microbiome-based interventions. Key studies include a clinical trial of FMT in 10 SS patients with dry eye, probiotic supplementation in 32 SS patients for oral candidiasis, and preclinical studies using engineered bacteria (e.g., R-2487) in murine SS models.

**Key Results:** - Gut dysbiosis in SS patients is characterized by increased Enterobacter and decreased Lachnospira, Roseburia, Bifidobacterium, Ruminococcus, and Blautia. Severe dysbiosis correlates with higher disease activity (ESSDAI and ClinESSDAI scores) and elevated fecal calprotectin. - In an open-label FMT trial, 5 of 10 SS patients reported improved dry eye symptoms, though no donor bacteria engraftment was observed. - Probiotic supplementation (Lactobacillus acidophilus, L. bulgaricus, Streptococcus thermophilus, Bifidobacterium bifidum) for 5 weeks in 32 SS patients significantly reduced oral candidal load (p < 0.05), but another study did not confirm this. - In a murine SS model, a 5-strain probiotic (L. casei, L. acidophilus, L. reuteri, B. bifidum, S. thermophilus) increased tear secretion after 3 weeks and reduced uveitis scores. - Engineered L. lactis expressing CFA/I fimbriae (R-2487) induced Tregs (Foxp3+, IL-10+, TGF-β+) and reduced inflammatory infiltration in salivary and lacrimal glands in murine SS models. - Probiotic supplementation in RA patients (a common comorbidity) improved clinical and metabolic status after 8 weeks.

**Clinical Implications:** The review underscores the potential of microbiome-based therapies as novel, safer alternatives to immunosuppressants for SS. Probiotics and FMT show promise for symptom relief (e.g., dry eye, oral candidiasis), while engineered bacteria like R-2487 offer precision immunomodulation by inducing regulatory T cells. However, most evidence is preclinical or from small trials; larger, randomized controlled trials are needed to confirm efficacy, safety, and mechanisms. The authors emphasize that synthetic biology approaches could overcome limitations of natural probiotics by selectively enhancing anti-inflammatory signals.

STUDY TYPE

narrative_review

SPECIALTY

ophthalmology

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AI pipeline

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ORIGINAL PAPER

PMC10270702

Sjögren’s Syndrome Treatments in the Microbiome Era

Advances in geriatric medicine and research

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ABSTRACT

Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by inflammatory cell infiltration of the salivary and lacrimal glands, resulting in acinar epithelial cell atrophy, cell death, and loss of exocrine function. At least half of SS patients develop extraglandular inflammatory disease and have a wide range of systemic clinical manifestations that can affect any organ system, including connective tissues. As many as 3.1 million people in the U.S. suffer from SS, a disease that causes severe impairment. Women are nine times more likely than men to be affected by this condition. Unfortunately, there is currently no effective treatment for SS, and the available options only provide partial relief. Treatment involves using replacement therapies such as artificial saliva and eye lubricants, or immunosuppressive agents that have limited efficacy. The medical community recognizes that there is a significant need for more effective treatments for SS. Increasing evidence demonstrates the links between the dysfunction of the human microbial community and the onset and development of many human diseases, signifying the potential use of microorganisms as an alternative strategy to conquer these issues. The role of the microbiome in controlling immune function of the human host in the context of autoimmune diseases like SS is now becoming better understood and may help to enable new drug development strategies. Natural probiotics and synthetic biology applications hold promise for novel treatment approaches to solve the encryption of many complex and multifactorial immune disorders, like SS.

CITATION EXPORT

Christian Furlan Freguia, David W. Pascual, Gary R. Fanger. Sjögren’s Syndrome Treatments in the Microbiome Era. Advances in geriatric medicine and research. (2023). https://doi.org/10.20900/agmr20230004

AUTHORS

3 · 2 CENTRES

Christian Furlan Freguia, David W. Pascual, Gary R. Fanger

1Rise Therapeutics, 1405 Research Blvd., Rockville, MD 20850, USA
2Department of Infectious Diseases & Immunology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611, USA