Fecal microbiota transfer from autoimmune dry eye disease model mice to conventional mice induces ocular surface inflammation and stereotypic B cell receptor repertoire development in lacrimal gland

In this study, we transferred gut microbiota of SS-like autoimmune dry eye disease model mice to conventional B6 mice (NOD-FMT). After the transfer, NOD-FMT mice experienced a dramatic change in the gut microbiomes and showed clinicopathological features of SS, including increased corneal fluorescein staining score, decreased tear production, elevated levels of IL-6 mRNA, decreased levels of MUC5AC mRNA encoding mucin. Additionally, we observed that NOD-FMT mice shared stereotypic B cell receptor (BCR) clonotypes with a much higher frequency compared to control group. B cell clones encoding these stereotypic BCR clonotypes developed and expanded locally in the lacrimal gland, and achieved systemic presence in certain clonotypes. Overall design: Feces were collected from 30 NOD.B10.H2b mice older than 20 weeks with autoimmune dry eye disease, and their microbiomes were transferred to ten mice (NOD-FMT group). In parallel, ten mice were orally gavaged with PBS (PBS-T group), and five mice from the same cohort received no treatment (NC group).