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. 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).