Exosomes from Limosilactobacillus fermentum Ameliorate Benzalkonium Chloride-Induced Inflammation in Conjunctival Cells

Dry eye is characterized by persistent instability and decreased tear production, which are accompanied by epithelial lesions and inflammation on the surface of the eye. In our previous paper, we reported that supplementation with <i>Limosilactobacillus fermentum</i> HY7302 (HY7302) could inhibit corneal damage in a benzalkonium chloride (BAC)-induced mouse model of dry eye, through its effects in gut microbiome regulation. The aim of this study was to determine what functional extracellular substances can alter the inflammatory response of conjunctival cells. We isolated exosomes from HY7302 probiotic culture supernatant, analyzed their morphological characteristics, and found that their average size was 143.8 ± 1.1 nm, which was smaller than the exosomes from the <i>L. fermentum</i> KCTC 3112 strain. In addition, HY7302-derived exosomes significantly reduced the levels of genes encoding pro-inflammatory cytokines, including <i>interleukin (IL)-20</i>, <i>IL-8</i>, <i>IL-6</i>, and <i>IL-1B</i>, in BAC-treated human conjunctival cells. Moreover, HY7302-derived exosomes significantly increased the levels of genes encoding tight junction proteins, including <i>TJP1</i>, <i>TJP2</i>, and <i>occludin-1</i>, in Caco-2 cells. Lastly, the HY7302 exosomes reduced mRNA expression levels of <i>IL1B</i>, <i>IL20</i>, <i>IL6</i>, <i>IL8</i>, and <i>NFAT5</i> in a transwell coculture system. Our findings indicate that HY7302 exosomes have potential for use in the treatment of ocular inflammation-related dry eye disease, through gut-eye axis communication via exosomes.