{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:46:27Z","timestamp":1790480787728,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,9,21]],"date-time":"2019-09-21T00:00:00Z","timestamp":1569024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FRN 126019"],"award-info":[{"award-number":["FRN 126019"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FRN 138657"],"award-info":[{"award-number":["FRN 138657"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000085","name":"Ontario HIV Treatment Network","doi-asserted-by":"publisher","award":["AHRC 779"],"award-info":[{"award-number":["AHRC 779"]}],"id":[{"id":"10.13039\/501100000085","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Approximately 40% of global HIV-1 transmission occurs in the female genital tract (FGT) through heterosexual transmission. Epithelial cells lining the FGT provide the first barrier to HIV-1 entry. Previous studies have suggested that certain hormonal contraceptives or a dysbiosis of the vaginal microbiota can enhance HIV-1 acquisition in the FGT. We examined the effects of lactobacilli and female sex hormones on the barrier functions and innate immune responses of primary endometrial genital epithelial cells (GECs). Two probiotic strains, Lactobacillus reuteri RC-14 and L. rhamnosus GR-1, were tested, as were sex hormones estrogen (E2), progesterone (P4), and the hormonal contraceptive medroxyprogesterone acetate (MPA). Our results demonstrate that probiotic lactobacilli enhance barrier function without affecting cytokines. Treatment of GECs with MPA resulted in reduced barrier function. In contrast, E2 treatment enhanced barrier function and reduced production of proinflammatory cytokines. Comparison of hormones plus lactobacilli as a pre-treatment prior to HIV exposure revealed a dominant effect of lactobacilli in preventing loss of barrier function by GECs. In summary, the combination of E2 and lactobacilli had the best protective effect against HIV-1 seen by enhancement of barrier function and reduction in proinflammatory cytokines. These studies provide insights into how probiotic lactobacilli in the female genital microenvironment can alter HIV-1-mediated barrier disruption and how the combination of E2 and lactobacilli may decrease susceptibility to primary HIV infection.<\/jats:p>","DOI":"10.3390\/cells8101120","type":"journal-article","created":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T03:26:32Z","timestamp":1569209192000},"page":"1120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Protective Effect of Probiotic Bacteria and Estrogen in Preventing HIV-1-Mediated Impairment of Epithelial Barrier Integrity in Female Genital Tract"],"prefix":"10.3390","volume":"8","author":[{"given":"Sara","family":"Dizzell","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University, Michael G. DeGroote Center for Learning and Discovery, Hamilton, ON L8P 3Z5, Canada"},{"name":"McMaster Immunology Research Center, McMaster University, Michael G. DeGroote Center for Learning and Discovery, Hamilton, ON L8S 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7410-9963","authenticated-orcid":false,"given":"Aisha","family":"Nazli","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University, Michael G. DeGroote Center for Learning and Discovery, Hamilton, ON L8P 3Z5, Canada"},{"name":"McMaster Immunology Research Center, McMaster University, Michael G. DeGroote Center for Learning and Discovery, Hamilton, ON L8S 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9658-5696","authenticated-orcid":false,"given":"Gregor","family":"Reid","sequence":"additional","affiliation":[{"name":"Departments of Microbiology &amp; Immunology and Surgery, Western University, and Canadian Research and Development Centre for Human Microbiome and Probiotics, The Lawson Health Research Institute, London, ON N6A 4V2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7088-2569","authenticated-orcid":false,"given":"Charu","family":"Kaushic","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University, Michael G. DeGroote Center for Learning and Discovery, Hamilton, ON L8P 3Z5, Canada"},{"name":"McMaster Immunology Research Center, McMaster University, Michael G. DeGroote Center for Learning and Discovery, Hamilton, ON L8S 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,21]]},"reference":[{"key":"ref_1","unstructured":"(2016, December 13). UNAIDS Gap Report 2014: Gender Based Inequalities. Available online: http:\/\/files.unaids.org\/en\/media\/unaids\/contentassets\/documents\/unaidspublication\/2014\/UNAIDS_Gap_report_en.pdf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s11904-009-0004-1","article-title":"HIV infection of the genital mucosa in women","volume":"6","author":"Hladik","year":"2009","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/cmi.2014.41","article-title":"Innate and adaptive immune responses in male and female reproductive tracts in homeostasis and following HIV infection","volume":"11","author":"Nguyen","year":"2014","journal-title":"Cell. Mol. 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