Dysbiotic gut microbiota from Sjögren’s syndrome patients or autoimmune dry eye mice transfer ocular surface inflammation into normal mice

Abstract

Purpose : To investigate the effect of fecal microbiota transplantation (FMT) from either Sjögren-like animal model or Sjögren’s syndrome patients on the ocular surface inflammation in C57BL/6 (B6) mouse model.

Methods : After fecal homogenization and antibiotics pretreatment, B6 mice were orally gavaged with feces from either NOD.B10.H2b mice (NOD) or Sjögren’s syndrome patients (SS), and as controls, either PBS or fecal fluid from healthy volunteers were given to B6 mice for 3 weeks (n=40). Corneal fluorescein staining (CFS) score, tear production, inflammatory cytokine level and activated conventional dendritic cell populations (cDCs) on ocular surface, compositional changes of the gut microbiome, and B cell receptor (BCR) repertoire analysis in lacrimal gland and spleen were analyzed.

Results : CFS score significantly increased in NOD- and SS-FMT group. Decreased tear production with higher IL-6 and lower Muc5AC on the ocular surface was found and increase in CD103⁺MHCII^hicDC2 and IFN-γ⁺T cells on the ocular surface were observed in NOD- and SS-FMT group. In genus level, the abundance of Parasutterella increased in both NOD- and SS-FMT group. The abundance of Alloprevotella, Blautia, Escherichia-Shigella, and Rhodospirillales increased in NOD-FMT group, whereas Muribaculaceae, Clostridia, Phascolarctobacterium, Monoglobus, and Paraprevotella increased in SS-FMT group. Highly shared specific clonotypes with high frequency of BCR were observed in lacrimal gland and spleen of NOD-FMT group, while shared BCR clonotypes was not prominent in SS-FMT group.

Conclusions : It shows cause-and-effect relationship indicating that dysbiosis of gut microbiome in Sjögren's syndrome or autoimmune dry eye mice can induce ocular surface inflammation by modulating either cDCs or BCR repertoires.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.