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

Abstract

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.

Systematic Review of the Effects of Exercise and Physical Activity on the Gut Microbiome of Older Adults

“…Regarding the taxa shown to be positively associated with an increased level of PA/exercise, the Actinobacteria phylum (which contains the genus Bifidobacterium ) has been reported to have positive effects on gut health such as inhibition of pathogens through the modulation of intestinal and immune responses [ 74 ], vitamin production [ 75 ], LPS reduction [ 77 ] and anti-inflammatory properties [ 76 ]. Members of the genus Prevotella are well-known SCFAs producers [ 97 ] and previous studies have found that higher amounts of exercise correlated positively with this genus [ 119 ]. However, there are contrasting results in the literature and some studies have shown that this genus might be associated with inflammation [ 96 ], consequently more research is needed in order to clarify the effects of Prevotella on the gut environment.…”

Aging effects on the diurnal patterns of gut microbial composition in male and female mice

“…The increased F/B ratio may have resulted from increased Firmicutes abundance, which was also reflected by the increased abundance of Lachnospiraceae NK4A136 group , which belongs to the phylum Firmicutes, at nighttime. Previous studies showed that the increase of F/B ratio was linked to increases of lipopolysaccharide levels in the plasma and feces of aged male mice [ 25 ], and increased abundance of Cyanobacteria in mice with high F/B ratio can be related to the severity of aging-associated dry eye [ 29 ]. We also observed the increases in F/B ratio and the relative abundance of Cyanobacteria in aged male mice at nighttime.…”

Time-Dependent Serial Changes of Antigen-Presenting Cell Subsets in the Ocular Surface Are Distinct between Corneal Sterile Inflammation and Allosensitization in a Murine Model

“…Balb/c female mice ( n = 54), which were 7 weeks old, were purchased from Orient Bio Inc. (Seongnam, Gyeonggi-do, Korea). The mice cages were in a specific pathogen-free facility at Seoul National University Hospital Biomedical Research Institute, maintained at 22–24 °C with 55% ± 5% relative humidity, and given food and water ad libitum [ 17 ]. The Balb/c mice were assigned to four groups: (1) control (Ct, n = 3 mice), (2) partial trephination group (PT, n = 5 mice), (3) syngeneic (Syn, n = 5 mice), and (4) allogeneic (Allo, n = 5 mice) corneal transplantation group, with one set for each time point ( n = 18 mice/week).…”