Lactobacillus plantarum and Bifidobacterium bifidum alleviate dry eye in mice with exorbital lacrimal gland excision by modulating gut inflammation and microbiota

In order to understand the efficacy of probiotics against dry eye syndrome, we selected anti-inflammatory probiotics Lactobacillus plantarum NK151 and Bifidobacterium bifidum NK175, which increased the ratio of IL-10 to TNF-α expression, from the human gut bacteria collection and examined their effects on tear secretion and cornea/conjunctiva inflammation in mice with excision of the unilateral exorbital lacrimal gland and 1% atropine and 0.1% benzalkonium chloride solution (ELA)-induced dry eye. Exposure to ELA significantly reduced tear secretion in mice, assessed by the phenol red thread tear test. However, oral gavage of NK151 and/or NK175 significantly increased ELA-suppressed tear secretion, IL-10 expression, and goblet cell population and decreased the ELA-induced corneal fluorescein-staining score, IL-1β and TNF-α expression in the conjunctiva. They also suppressed ELA-induced myeloperoxidase, IL-1β, and TNF-α expression. In particular, they increased the ratio of IL-10 to TNF-α expression in the colon. Their treatments increased ELA-induced α-diversity reduction to that of the control group and partially restored ELA-shifted β-diversity to that of the control group. Oral gavage of NK151 and/or NK175 reduced ELA-induced Verrucomicrobia and Actinobacteria populations at the phylum level. Furthermore, they reduced ELA-induced Bacteroidaceae, Akkemansiaceae, and AC160630_f populations and increased ELA-suppressed Lactobacillaceae and Muribaculaceae populations at the family level. These gut bacteria populations exhibited significant correlation with the tear secretion volume. In conclusion, NK151 and/or NK175 alleviated dry eye by modulating the expression ratio of pro-inflammatory cytokines such as TNF-α and anti-inflammatory cytokines such as IL-10 and gut microbiota composition.