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Gut microbial alterations associated with the exacerbation of experimental autoimmune uveitis in PGRN-deficient mice

Year: 2026

Type: article

Abstract: Purpose Progranulin (PGRN) has been shown to play a protective role in the development of a variety of immune-mediated diseases, and the gut microbiome has been implicated in the pathogenesis of autoimmune diseases. In this study, we investigate the changes in the gut microbiota and their association with the severity of experimental autoimmune uveitis (EAU) in PGRN-deficient mice. Methods WT and PGRN-deficient C57BL/6 mice were used to induce EAU using interphotoreceptor-binding protein peptide. Gastrointestinal (GI) contents collected from both groups of induced EAU were subjected to 16S rRNA gene sequencing analysis. Results PGRN-deficient mice developed exacerbated EAU compared to wild-type (WT) mice. The microbial richness of the GI contents in PGRN-deficient EAU mice was significantly lower than in WT mice. The PGRN-deficient EAU mice showed a significantly reduced microbial abundance in five phyla, namely, Cyanobacteria , Epsilonbacteraeota , Firmicutes , Nitrospirae , and Patescibacteria , and a significantly increased abundance in the other four phyla, namely, Deferribacteres , Proteobacteria , Spirochaetes , and Tenericutes . More importantly, a newly emerged phylum named Chlamydiae was detected in the gut microbial community of PGRN-deficient EAU mice. The histopathological scores were significantly negatively correlated with gut microbial abundance and significantly positively correlated with chlamydial abundance. Conclusion Our results showed that PGRN plays a protective role in EAU, and the significant changes in the gut microbiome may be associated with the exacerbation of inflammation in the PGRN-deficient EAU mice.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1641755

Authors: Wenjun Zhou, Song Zhang, Chaokui Wang

Institutions: The Affiliated Yongchuan Hospital of Chongqing Medical University, State Key Laboratory of Pollution Control and Resource Reuse, Nanjing University

Language: English

Topic: Ocular Diseases and Behçet’s Syndrome

Subfield: Ophthalmology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801