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

Abstract

Objective To investigate the clinical effects of IRT5 probiotics in the environmental dry eye model. Methods Eight week old male C57BL/6 mice were randomly divided into two groups; control group (n = 16) received oral gavage of 300 μL phosphate-buffered saline (PBS) alone once daily, IRT5 group (n = 9) received oral gavage of 1 x 109 CFU IRT5 probiotics powder in 300 μL PBS once daily, both groups for 11 to 12 days. Simultaneously, all mice underwent dry eye induction. Tear secretion, corneal staining and conjunctival goblet cell density were evaluated. Quantative real-time polymerase chain reaction (RT-PCR) for inflammation-related markers was performed. 16S ribosomal RNA of fecal microbiome was analyzed and compositional difference, alpha and beta diversities were assessed. Results There was no difference in NEI score but significant increase in tear secretion was observed in IRT5 group (p < 0.001). There was no significant difference in goblet cell density between groups. Quantative RT-PCR of cornea and conjunctiva revealed increased TNF-α expression in IRT5 group (p < 0.001) whereas other markers did not significantly differ from control. IRT5 group had significantly increased species diversity by Shannon index (p = 0.041). Beta diversity of genus by UniFrac principle coordinates analysis showed significant distance between groups (p = 0.001). Compositional differences between groups were observed and some were significantly associated with tear secretion. Multivariate linear regression analysis revealed Christensenellaceae (p = 0.009), Lactobacillus Helveticus group (p = 0.002) and PAC001797_s (p = 0.011) to strongly influence tear secretion. Conclusion In experimental dry eye model, IRT5 probiotics treatment partially improves experimental dry eye by increasing tear secretion which was associated with and influenced by the change in intestinal microbiome. Also, intestinal microbiome may affect the lacrimal gland through a different mechanism other than regulating inflammation.

Gut microbiota and eye diseases: a bibliometric study and visualization analysis

“…The majority of the articles from cluster #4 are about the regulation of ocular surface health and ocular surface diseases such as Sjogren’s syndrome and dry eye syndrome ( de Paiva et al., 2016 ; Kugadas et al., 2017 ; Schaefer et al., 2022b ). And over half of these representative citing articles in this section ( Table 8 ) were completed by Moon J and colleagues, including two original articles and one review ( Moon et al., 2020a ; Moon et al., 2020b ; Moon et al., 2020c ). Of note, IRT5, a mixed probiotic consisting of Lactobacillus casei , Lactobacillus acidophilus , Lactobacillus reuteri , Bifidobacterium bifidum , and Streptococcus thermophilus , was mentioned to potentially decrease the severity of experimental dry eye model, which indicated that probiotics might be an effective means to treat disease by intervening with the gut microbiota ( Kim et al., 2017 ; Moon et al., 2020b ).…”

“…And over half of these representative citing articles in this section ( Table 8 ) were completed by Moon J and colleagues, including two original articles and one review ( Moon et al., 2020a ; Moon et al., 2020b ; Moon et al., 2020c ). Of note, IRT5, a mixed probiotic consisting of Lactobacillus casei , Lactobacillus acidophilus , Lactobacillus reuteri , Bifidobacterium bifidum , and Streptococcus thermophilus , was mentioned to potentially decrease the severity of experimental dry eye model, which indicated that probiotics might be an effective means to treat disease by intervening with the gut microbiota ( Kim et al., 2017 ; Moon et al., 2020b ). In contrast, there is less attention to cluster #6 (graves’ orbitopathy), which is isolated from other clusters in the cluster map ( Figure 6A ).…”

Sjögren’s Syndrome Treatments in the Microbiome Era

“…In a similar preclinical model, administration of Lactobacillus plantarum and Bifidobacterium bifidum modulated the expression of proinflammatory cytokines such as TNF-α and anti-inflammatory cytokines such as IL-10 and gut microbiota composition to improve the disease severity [ 97 ]. In yet another preclinical study, administration of the same 5 commensal strains ( Lactobacillus casei , Lactobacillus acidophilus , Lactobacillus reuteri , Bifidobacterium bifidum , and Streptococcus thermophilus ) in a SS mouse model significantly increased tear secretion after 3 weeks treatment by modulating the host immune response [ 98 ].…”

Age-Dependent Distinct Distributions of Dendritic Cells in Autoimmune Dry Eye Murine Model

“…Corneal staining was observed using a microscope (Olympus SZ61; Olympus Corporation, Tokyo, Japan). The B6 and NOD.B10.H2b mice were observed using cobalt blue and white light (LED) illumination, respectively [26,33]. For the tear secretion test, phenol red-impregnated cotton threads (FCI Ophthalmics, Pembroke, MA, USA) were placed into the lateral canthus of mice for 60 s. The average values of corneal staining scores and tear secretion results from both eyes of each mouse were used for the statistical analyses based on a protocol described in a previous study [34].…”