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Association between aging-dependent gut microbiome dysbiosis and dry eye severity in C57BL/6 male mouse model: a
Chang Ho Yoon1,2,3, Jin Suk Ryu3, Jayoon Moon1,2,3
1Department of Ophthalmology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
Background:
While 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.
Results:
Eight-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.
Conclusions:
Our pilot study suggests that aging-dependent changes in microbiome composition are related to severity of dry eye signs in C57BL/6 male mice.
Insights
Aging alters gut microbiota, which is linked to dry eye disease severity in mice. These microbiome changes may contribute to age-related dry eye symptoms.
Area of Science:
- Microbiology
- Ophthalmology
- Gerontology
Background:
- Aging is a significant risk factor for dry eye disease.
- Age-related gut dysbiosis is linked to inflammation and geriatric diseases.
- Gut dysbiosis may exacerbate ocular conditions, including dry eye disease.
Purpose of the Study:
- To investigate the association between aging-dependent gut microbiome alterations and dry eye severity.
- To explore the role of gut microbiota changes in the pathophysiology of age-related dry eye disease.
Main Methods:
- A pilot study using C57BL/6 male mice of three age groups: 8-week-old, 1-year-old, and 2-year-old.
- Assessment of dry eye severity through corneal staining and tear secretion measurements.
- Analysis of fecal bacterial 16S rRNA for microbiome composition and diversity (α- and β-diversity).
Main Results:
- Aged mice exhibited significantly increased corneal staining and decreased tear secretion.
- While α-diversity remained unchanged, β-diversity of the gut microbiome differed significantly across age groups.
- Specific bacterial phyla (Firmicutes, Proteobacteria, Cyanobacteria), the Firmicutes/Bacteroidetes ratio, and genera (Alistipes, Bacteroides, Prevotella, Paraprevotella, Helicobacter, Lactobacillus) were significantly associated with dry eye severity after age adjustment.
Conclusions:
- Aging-dependent changes in gut microbiome composition are associated with the severity of dry eye signs in mice.
- This pilot study highlights a potential link between gut dysbiosis and age-related dry eye disease.

