Effect of probiotics on aging-dependent gut dysbiosis in autoimmune dry eye mouse model

Abstract

Purpose : To investigate the aging dependent changes of gut microbiome related to dry eye manifestations and to evaluate whether probiotics may reverse gut dysbiosis and dry eye in autoimmune dry eye mouse model

Methods : Fecal microbiome of NOD.B10.H2^b mice at 10-, 13-, 16- and 20-week old were analyzed with V3 to V4 region of 16S ribosomal RNA gene. Phenol red cotton thread test, corneal fluorescein staining (CFS) score were also investigated. Thereafter, 13-week old NOD.B10.H2^b mice divided into 2 groups and were gavaged with either PBS or probiotics (BN-77) for 3 weeks. Fecal microbiome, tear secretion, CFS score, inflammatory foci score in lacrimal gland, ocular surface cytokines by RT-PCR were analyzed.

Results : While tear secretion had decreased consistently, CFS score increased over time. Beta-diversity was significantly distinct among the different-aged groups, and abundance of Firmicutes continuingly decreased over time in phylum level. In genus levels, as abundance of Bifidobacterium maintained less than 1% through the whole aging, proportions of Prevotellaceae, Odoribacter, Bacteroides and Lachnoanaerobaculum were prevailing over time. Abundances of Lactobacillus and Eubacterium decreased after 13 weeks. After probiotics treatment, CFS score was significantly reduced whereas tear production and inflammatory foci score of lacrimal gland were not changed. TNF-α of ocular surface was significantly lower in probiotics-treated group. Although no changes were seen in abundance of Bifidobacterium, proportions of Odoribacter, Bacteroides, and Lachnoanaerobaculum were significantly reduced with increase of Lactobacillus abundance after probiotics treatment.

Conclusions : Administration of probiotics (BN-77) may have an effect mostly on aging-dependent dysbiosis that seems to be involved in ocular surface inflammation of autoimmune dry eye model.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.