Aging Is Associated With Decreased Lactobacillus and Increased Cervicovaginal Inflammation in Canadian Women

Abstract

Problem

Aging is characterized by a general dysregulation of systemic immune responses that increases susceptibility to infections and malignancies. Immune cells in the female genital tract (FGT) are regulated by sex hormones, but little is known about the impact of aging and menopause on immunology in the FGT.

Method of Study

This study conducted an age-focused sub-analysis of cervicovaginal samples collected from 47 women enrolled in the Vaginal Mucosal Systems study in Winnipeg, Canada. Paired cervicovaginal lavage and cervical cytobrush were collected and analyzed by Luminex cytokine array, mass spectrometry based metaproteomics, metabolomics, and high dimensional flow cytometry.

Results

The median age of study participants was 38 (range 19–88), with 12 over the age of 50. Increasing age was significantly correlated with increased cervicovaginal inflammation, including inflammatory cytokine MIP-1β (r = 0.335, p = 0.023), and activated T cells (CD4+HLA-DR+ r = 0406, p = 0.009; CD8+HLA-DR+ r = 0.399, p = 0.010; CD8+CD38+HLA-DR+ r = 0.386, p = 0.013). Proteomic analysis of cervicovaginal mucus identified 925 human proteins, with 108 (11.7%) significantly correlated with age. Pathway analysis indicated biofunctions related to immune response, migration, and myeloid cell phagocytosis increased with age. Interestingly, neutrophil related pathways decreased with age, including G-CSF (r = −0.396, p = 0.006) and reactive oxygen species (z-score = −2.607, p = 2.31E-4). Vaginal Lactobacillus crispatus, a species associated with mucosal health, significantly decreased with age (r = −0.340, p = 0.022), with participants over the age of 50 more likely to have non-Lactobacillus dominant microbiomes compared to those under 40.

Conclusions

Together, our data suggests that there is an increase in cervicovaginal inflammation and a decrease in L. crispatus that occurs with aging.