IRT5 Probiotics Changes Immune Modulatory Protein Expression in the Extraorbital Lacrimal Glands of an Autoimmune Dry Eye Mouse Model

Abstract

Purpose While the association between the gut microbiome and the immune system has been studied in autoimmune disorders, little is known about ocular disease. Previously we reported that IRT5, a mixture of five probiotic strains, could suppress autoimmune dry eye. In this study, we investigated the mechanism by which IRT5 performs its immunomodulatory function in a mouse model of autoimmune dry eye. Methods NOD.B10.H2b mice were used as an autoimmune dry eye model. Either IRT5 or PBS was gavaged orally for 3 weeks, with or without 5 days of antibiotic pretreatment. The effects on clinical features, extraorbital lacrimal gland and spleen proteins, and fecal microbiota were analyzed. Results The ocular staining score was lower, and tear secretion was higher, in the IRT5-treated groups than in the PBS-treated groups. After IRT5 treatment, the downregulated lacrimal gland proteins were enriched in the biological processes of defense response and immune system process. The relative abundances of 33 operational taxonomic units were higher, and 53 were lower, in the feces of the IRT5-treated groups than in those of the PBS-treated groups. IRT5 administration without antibiotic pretreatment also showed immunomodulatory functions with increases in the Lactobacillus helveticus group and Lactobacillus hamsteri . Additional proteomic assays revealed a decrease of proteins related to antigen-presenting processes in the CD11b + and CD11c + cells of spleen in the IRT5-treated groups. Conclusions Changes in the gut microbiome after IRT5 treatment improved clinical manifestations in the autoimmune dry eye model via the downregulation of antigen-presenting processes in immune networks.

Can Gut Microbiota Affect Dry Eye Syndrome?

“…Lymphocytic infiltration in LG of germ-free mouse diminished after fecal transplantation [ 84 ]. Likewise, we observed that probiotics enhanced the expression of lacrimal immunomodulatory proteins in a Sjögren-like mice model [ 86 ].…”

“…Two studies have observed that a probiotic composed of L. casei , L . acidophilus , L. reuteri , B. bifidum , and S. thermophiles for 3 weeks in NOD mice restored corneal barrier disruption and increased tear secretion [ 86 , 126 ]. We noticed a decrease in inflammatory cell infiltration in LG and CD8 + IFN-γ Hi cells in the lymph nodes, while T reg cells increased [ 126 ].…”

“…We noticed a decrease in inflammatory cell infiltration in LG and CD8 + IFN-γ Hi cells in the lymph nodes, while T reg cells increased [ 126 ]. While using the same probiotic in the same SS model, Choi et al observed that proteins related with antigen presentation decreased in the LGs [ 86 ].…”

“…Finally, given that neuropeptides, such as neuropeptide Y, substance P, vasoactive intestinal polypeptide, and calcitonin gene-related peptide, have been observed in the gut–brain axis [ 53 , 137 ] and the critical roles of several neuropeptides, including the above mentioned, taken place in stimulating LG tear secretion [ 87 ], the disturbances of gut-derived neuropeptides can control LG secretion. Therefore, this is considered as the last hidden mechanism for increased tear secretion seen in animal and human studies with pre- and probiotics administration [ 86 , 125 , 126 , 127 , 128 , 129 ] (neuropeptide circulation theory).…”

Effect of IRT5 probiotics on dry eye in the experimental dry eye mouse model

“…We have also demonstrated IRT5 probiotics’ beneficial effects of alleviating clinical manifestations in autoimmune uveitis and autoimmune dry eye models [ 24 ]. More recently, we observed that IRT5 probiotics acts via downregulation of antigen-presenting processes in the immune network [ 25 ].…”