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. 2025 Feb;93(2):e70058.
doi: 10.1111/aji.70058.

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

Ha T Dang  1 , Laura Noel-Romas  1   2 , Samantha Knodel  1   2 , Kenzie Birse  1 , Alana Lamont  3 , Kateryna Kratzer  3 , Peter McQueen  4 , Michelle Perner  4 , Hossaena Ayele  1   3 , Alicia R Berard  1   2 , John J Schellenberg  3 , Stuart McCorrister  4 , Garrett Westmacott  4 , Bonnie Sandberg  5 , Adelicia Yu  2 , Margaret Burnett  2 , Vanessa Poliquin  2 , Adam D Burgener  1   2   6 , Christina Farr Zuend  1
Affiliations

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

Ha T Dang et al. Am J Reprod Immunol. 2025 Feb.

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.

Keywords: aging; cervicovaginal microenvironment; women's health.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Overview of study participant age groups (n = 47).
FIGURE 2
FIGURE 2
Nineteen genera of bacteria were identified from CVL sample by mass spectrometry with 1758 unique bacterial proteins detected. (a) Proportion plot of bacterial taxa detected. Each column represents a participant. Participants are arranged by age. (b) Correlation between L. crispatus level and age (n = 45).
FIGURE 3
FIGURE 3
Inflammatory cytokines were detected in CVL and correlated with age. (a) MIP‐1β. (b) G‐CSF. n = 46.
FIGURE 4
FIGURE 4
Cervical leukocytes were isolated from cervical cytobrushes and immunophenotypes by flow cytometry, and levels of cells were correlated with age (n = 41).
FIGURE 5
FIGURE 5
(a) Host proteins were identified in CVL using mass spectrometry. Unsupervised hierarchical clustering of proteins significantly correlated with age indicated older participants with non‐Lactobacillus dominant microbiome clustered together. (b) Ingenuity pathway analysis was used to identify biofunctions significantly associated with aging (activation z score ± 2, p < 0.05) (n = 47).
FIGURE 6
FIGURE 6
Metabolites were identified in CVL. Unsupervised hierarchical clustering of metabolites significantly correlated with age indicated older participants with non‐Lactobacillus dominant microbiome clustered together (n = 43).
See this image and copyright information in PMC

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