Association between aging-dependent gut microbiome dysbiosis and dry eye severity in C57BL/6 male mouse model: a pilot study

Chang Ho Yoon,Jayoon Moon,Mee Kum Kim,Jin Suk Ryu

doi:10.1186/s12866-021-02173-7

Chang Ho Yoon, Jayoon Moon + Show 2 more

Open Access

https://doi.org/10.1186/s12866-021-02173-7

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Abstract

BackgroundWhile aging is a potent risk factor of dry eye disease, age-related gut dysbiosis is associated with inflammation and chronic geriatric diseases. Emerging evidence have demonstrated that gut dysbiosis contributes to the pathophysiology or exacerbation of ocular diseases including dry eye disease. However, the relationship between aging-related changes in gut microbiota and dry eye disease has not been elucidated. In this pilot study, we investigated the association between aging-dependent microbiome changes and dry eye severity in C57BL/6 male mice.ResultsEight-week-old (8 W, n = 15), one-year-old (1Y, n = 10), and two-year-old (2Y, n = 8) C57BL/6 male mice were used. Dry eye severity was assessed by corneal staining scores and tear secretion. Bacterial genomic 16 s rRNA from feces was analyzed. Main outcomes were microbiome compositional differences among the groups and their correlation to dry eye severity. In aged mice (1Y and 2Y), corneal staining increased and tear secretion decreased with statistical significance. Gut microbiome α-diversity was not different among the groups. However, β-diversity was significantly different among the groups. In univariate analysis, phylum Firmicutes, Proteobacteria, and Cyanobacteria, Firmicutes/Bacteroidetes ratio, and genus Alistipes, Bacteroides, Prevotella, Paraprevotella, and Helicobacter were significantly related to dry eye severity. After adjustment of age, multivariate analysis revealed phylum Proteobacteria, Firmicutes/Bacteroidetes ratio, and genus Lactobacillus, Alistipes, Prevotella, Paraprevotella, and Helicobacter to be significantly associated with dry eye severity.ConclusionsOur pilot study suggests that aging-dependent changes in microbiome composition are related to severity of dry eye signs in C57BL/6 male mice.

Highlights

While aging is a potent risk factor of dry eye disease, age-related gut dysbiosis is associated with inflammation and chronic geriatric diseases
The amount of tear secretion was not different among the groups; whereas, the correction value according to body weight (BW), which is clinically relevant, was significantly lower in both One-year old (1Y) and 2Y groups than in the 8 W group (Fig. 1c; p = 0.003 and p = 0.044, respectively; Kruskal–Wallis test followed by Dunn’s post hoc test)
This study demonstrates that (1) aging-dependent gut dysbiosis is present in B6 male mouse model and (2) dry eye severity is correlated with the gut dysbiosis

Summary

Introduction

While aging is a potent risk factor of dry eye disease, age-related gut dysbiosis is associated with inflammation and chronic geriatric diseases. The relationship between agingrelated changes in gut microbiota and dry eye disease has not been elucidated. In this pilot study, we investigated the association between aging-dependent microbiome changes and dry eye severity in C57BL/6 male mice. Tear film instability and ocular surface inflammation may contribute to the disease [1, 2]. Tear film instability induces hyperosmolar stress in ocular surface epithelium, which subsequently acts as an initial precipitating factor for dry eye disease. Hyperosmolar stress promotes the expression of inflammatory cytokines in the damaged ocular surface epithelium [1]. Regulatory T cell (Treg) dysfunction is involved in the progression to chronic dry eye disease [7]

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