{"doi":"10.1111/aji.70058","title":"Aging Is Associated With Decreased <i>Lactobacillus</i> and Increased Cervicovaginal Inflammation in Canadian Women","abstract":"<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Problem</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Method of Study</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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 (<jats:italic>r</jats:italic> = 0.335, <jats:italic>p</jats:italic> = 0.023), and activated T cells (CD4+HLA‐DR+ <jats:italic>r</jats:italic> = 0406, <jats:italic>p</jats:italic> = 0.009; CD8+HLA‐DR+ <jats:italic>r</jats:italic> = 0.399, <jats:italic>p</jats:italic> = 0.010; CD8+CD38+HLA‐DR+ <jats:italic>r</jats:italic> = 0.386, <jats:italic>p</jats:italic> = 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 (<jats:italic>r</jats:italic> = −0.396, <jats:italic>p</jats:italic> = 0.006) and reactive oxygen species (<jats:italic>z</jats:italic>‐score = −2.607, <jats:italic>p</jats:italic> = 2.31E‐4). Vaginal <jats:italic>Lactobacillus crispatus</jats:italic>, a species associated with mucosal health, significantly decreased with age (<jats:italic>r</jats:italic> = −0.340, <jats:italic>p</jats:italic> = 0.022), with participants over the age of 50 more likely to have non‐<jats:italic>Lactobacillus</jats:italic> dominant microbiomes compared to those under 40.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Together, our data suggests that there is an increase in cervicovaginal inflammation and a decrease in <jats:italic>L. crispatus</jats:italic> that occurs with aging.</jats:p></jats:sec>","journal":"American Journal of Reproductive Immunology","year":2025,"id":613360,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1580146,"name":"Laura Noel‐Romas","orcid":null,"position":1,"is_corresponding":false},{"id":808631,"name":"Samantha Knodel","orcid":null,"position":2,"is_corresponding":false},{"id":544213,"name":"Kenzie Birse","orcid":"0000-0002-7503-020X","position":3,"is_corresponding":false},{"id":314044,"name":"Alana Lamont","orcid":"0000-0003-0431-7825","position":4,"is_corresponding":false},{"id":315891,"name":"Kateryna Kratzer","orcid":null,"position":5,"is_corresponding":false},{"id":1580147,"name":"Peter McQueen","orcid":null,"position":6,"is_corresponding":false},{"id":1027714,"name":"Michelle Perner","orcid":"0000-0001-7881-2867","position":7,"is_corresponding":false},{"id":934572,"name":"Hossaena Ayele","orcid":null,"position":8,"is_corresponding":false},{"id":544212,"name":"Alicia R. Berard","orcid":"0000-0002-2210-0577","position":9,"is_corresponding":false},{"id":1580148,"name":"John J. Schellenberg","orcid":null,"position":10,"is_corresponding":false},{"id":381839,"name":"Stuart McCorrister","orcid":null,"position":11,"is_corresponding":false},{"id":381840,"name":"Garrett Westmacott","orcid":null,"position":12,"is_corresponding":false},{"id":1580149,"name":"Bonnie Sandberg","orcid":null,"position":13,"is_corresponding":false},{"id":1580150,"name":"Adelicia Yu","orcid":null,"position":14,"is_corresponding":false},{"id":1580151,"name":"Margaret Burnett","orcid":null,"position":15,"is_corresponding":false},{"id":314051,"name":"Vanessa Poliquin","orcid":"0000-0003-0526-3902","position":16,"is_corresponding":false},{"id":897674,"name":"Adam D. Burgener","orcid":null,"position":17,"is_corresponding":false},{"id":314043,"name":"Christina Farr Zuend","orcid":"0009-0001-4165-6909","position":18,"is_corresponding":false},{"id":1580145,"name":"Ha T. Dang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Aging Is Associated With Decreased <i>Lactobacillus</i> and Increased Cervicovaginal Inflammation in Canadian Women","abstract":"<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Problem</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Method of Study</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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 (<jats:italic>r</jats:italic> = 0.335, <jats:italic>p</jats:italic> = 0.023), and activated T cells (CD4+HLA‐DR+ <jats:italic>r</jats:italic> = 0406, <jats:italic>p</jats:italic> = 0.009; CD8+HLA‐DR+ <jats:italic>r</jats:italic> = 0.399, <jats:italic>p</jats:italic> = 0.010; CD8+CD38+HLA‐DR+ <jats:italic>r</jats:italic> = 0.386, <jats:italic>p</jats:italic> = 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 (<jats:italic>r</jats:italic> = −0.396, <jats:italic>p</jats:italic> = 0.006) and reactive oxygen species (<jats:italic>z</jats:italic>‐score = −2.607, <jats:italic>p</jats:italic> = 2.31E‐4). Vaginal <jats:italic>Lactobacillus crispatus</jats:italic>, a species associated with mucosal health, significantly decreased with age (<jats:italic>r</jats:italic> = −0.340, <jats:italic>p</jats:italic> = 0.022), with participants over the age of 50 more likely to have non‐<jats:italic>Lactobacillus</jats:italic> dominant microbiomes compared to those under 40.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Together, our data suggests that there is an increase in cervicovaginal inflammation and a decrease in <jats:italic>L. crispatus</jats:italic> that occurs with aging.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23304386","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"Canadian Institutes of Health Research","grant_id":"unidentified","title":"unidentified"}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"hybrid","license":"cc-by-nc","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/aji.70058","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/aji.70058","host_type":"publisher"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11836769/pdf/AJI-93-e70058.pdf","host_type":"repository"},{"url":"https://commons.case.edu/facultyworks/1323","host_type":""},{"url":"https://doi.org/10.1111/aji.70058","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/39968674","host_type":""},{"url":"http://dx.doi.org/10.1111/aji.70058","host_type":""}],"fields_of_study":["0301 basic medicine","03 medical and health sciences"],"mesh_terms":[],"keywords":["Adult","Aged, 80 and over","Inflammation","Aging","Canada","Cervix Uteri","Middle Aged","Lactobacillus","Young Adult","Vagina","Humans","Cytokines","Original Article","Female","Aged"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T07:47:03.773692Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}