Cargando…

The Impact of Over-The-Counter Lactic Acid Containing Vaginal Gels on the Integrity and Inflammatory State of the Vaginal Epithelium in vitro

The vaginal microbiome influences a wide range of health outcomes in women, where a microbiome dominated by Lactobacillus spp. is considered optimal and associated with reduced risk of pre-term birth and acquisition of sexually transmitted infections including HIV. Conversely, replacement of lactoba...

Descripción completa

Detalles Bibliográficos
Autores principales: Tyssen, David, Hearps, Anna C., Guntur, Kalyani, Masson, Lindi, Cook, Simon, Moulton, Simon E., Ravel, Jacques, Bradshaw, Catriona S., Ayehunie, Seyoum, Tachedjian, Gilda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580709/
https://www.ncbi.nlm.nih.gov/pubmed/36303665
http://dx.doi.org/10.3389/frph.2022.915948
_version_ 1784812449731444736
author Tyssen, David
Hearps, Anna C.
Guntur, Kalyani
Masson, Lindi
Cook, Simon
Moulton, Simon E.
Ravel, Jacques
Bradshaw, Catriona S.
Ayehunie, Seyoum
Tachedjian, Gilda
author_facet Tyssen, David
Hearps, Anna C.
Guntur, Kalyani
Masson, Lindi
Cook, Simon
Moulton, Simon E.
Ravel, Jacques
Bradshaw, Catriona S.
Ayehunie, Seyoum
Tachedjian, Gilda
author_sort Tyssen, David
collection PubMed
description The vaginal microbiome influences a wide range of health outcomes in women, where a microbiome dominated by Lactobacillus spp. is considered optimal and associated with reduced risk of pre-term birth and acquisition of sexually transmitted infections including HIV. Conversely, replacement of lactobacilli by non-optimal bacteria leads to the development of bacterial vaginosis, which is associated with increased risk of these outcomes. Lactobacilli produce the metabolite lactic acid (LA) which is a potent antibacterial and antiviral agent. The potential therapeutic benefits of LA have prompted the development of numerous over-the-counter LA-containing gels for use in the vagina, although a comprehensive analysis of the impact of these formulations on the cervicovaginal epithelium and pro-inflammatory cytokine/chemokine responses, has not been assessed. Here, we evaluated the properties of 11 over-the-counter gels, including 9 containing LA, marketed for use in the vagina. Ten of the 11 gels had an osmolality greater than vaginal fluid from women with Lactobacillus-dominated microbiota (370 ± 40 mOsmol/kg in women with Nugent score 0–3), with six gels that were hyperosmolal >2,000 mOsmol/kg. Using a reconstructed primary cell model of the vaginal epithelium, we found hyperosmolal gels had a detrimental impact on epithelial barrier integrity, resulting in substantial cellular toxicity (<10% viability as compared to untreated cells) and reduced epithelial barrier integrity [≈30% of untreated cells, assessed by transepithelial electrical resistance (TEER)]. Treatment of vaginal tissues with most of the gels elicited the production of pro-inflammatory factors including IL-1α (8 of 11) and IL-1β (10 of 11) which are associated with heightened risk of HIV acquisition in vivo. The majority of the OTC gels elicited moderate tissue damage as determined by histology. The detrimental effects of these gels on the human vaginal epithelium in vitro may predict compromised epithelial barrier integrity and genital inflammation in vivo, which has implications for sexual and reproductive health. This study highlights the importance of evaluating the impact of intravaginal products on the integrity and inflammatory status of the mucosal epithelium to avoid unfavorable off target effects.
format Online
Article
Text
id pubmed-9580709
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-95807092022-10-26 The Impact of Over-The-Counter Lactic Acid Containing Vaginal Gels on the Integrity and Inflammatory State of the Vaginal Epithelium in vitro Tyssen, David Hearps, Anna C. Guntur, Kalyani Masson, Lindi Cook, Simon Moulton, Simon E. Ravel, Jacques Bradshaw, Catriona S. Ayehunie, Seyoum Tachedjian, Gilda Front Reprod Health Reproductive Health The vaginal microbiome influences a wide range of health outcomes in women, where a microbiome dominated by Lactobacillus spp. is considered optimal and associated with reduced risk of pre-term birth and acquisition of sexually transmitted infections including HIV. Conversely, replacement of lactobacilli by non-optimal bacteria leads to the development of bacterial vaginosis, which is associated with increased risk of these outcomes. Lactobacilli produce the metabolite lactic acid (LA) which is a potent antibacterial and antiviral agent. The potential therapeutic benefits of LA have prompted the development of numerous over-the-counter LA-containing gels for use in the vagina, although a comprehensive analysis of the impact of these formulations on the cervicovaginal epithelium and pro-inflammatory cytokine/chemokine responses, has not been assessed. Here, we evaluated the properties of 11 over-the-counter gels, including 9 containing LA, marketed for use in the vagina. Ten of the 11 gels had an osmolality greater than vaginal fluid from women with Lactobacillus-dominated microbiota (370 ± 40 mOsmol/kg in women with Nugent score 0–3), with six gels that were hyperosmolal >2,000 mOsmol/kg. Using a reconstructed primary cell model of the vaginal epithelium, we found hyperosmolal gels had a detrimental impact on epithelial barrier integrity, resulting in substantial cellular toxicity (<10% viability as compared to untreated cells) and reduced epithelial barrier integrity [≈30% of untreated cells, assessed by transepithelial electrical resistance (TEER)]. Treatment of vaginal tissues with most of the gels elicited the production of pro-inflammatory factors including IL-1α (8 of 11) and IL-1β (10 of 11) which are associated with heightened risk of HIV acquisition in vivo. The majority of the OTC gels elicited moderate tissue damage as determined by histology. The detrimental effects of these gels on the human vaginal epithelium in vitro may predict compromised epithelial barrier integrity and genital inflammation in vivo, which has implications for sexual and reproductive health. This study highlights the importance of evaluating the impact of intravaginal products on the integrity and inflammatory status of the mucosal epithelium to avoid unfavorable off target effects. Frontiers Media S.A. 2022-06-23 /pmc/articles/PMC9580709/ /pubmed/36303665 http://dx.doi.org/10.3389/frph.2022.915948 Text en Copyright © 2022 Tyssen, Hearps, Guntur, Masson, Cook, Moulton, Ravel, Bradshaw, Ayehunie and Tachedjian. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Reproductive Health
Tyssen, David
Hearps, Anna C.
Guntur, Kalyani
Masson, Lindi
Cook, Simon
Moulton, Simon E.
Ravel, Jacques
Bradshaw, Catriona S.
Ayehunie, Seyoum
Tachedjian, Gilda
The Impact of Over-The-Counter Lactic Acid Containing Vaginal Gels on the Integrity and Inflammatory State of the Vaginal Epithelium in vitro
title The Impact of Over-The-Counter Lactic Acid Containing Vaginal Gels on the Integrity and Inflammatory State of the Vaginal Epithelium in vitro
title_full The Impact of Over-The-Counter Lactic Acid Containing Vaginal Gels on the Integrity and Inflammatory State of the Vaginal Epithelium in vitro
title_fullStr The Impact of Over-The-Counter Lactic Acid Containing Vaginal Gels on the Integrity and Inflammatory State of the Vaginal Epithelium in vitro
title_full_unstemmed The Impact of Over-The-Counter Lactic Acid Containing Vaginal Gels on the Integrity and Inflammatory State of the Vaginal Epithelium in vitro
title_short The Impact of Over-The-Counter Lactic Acid Containing Vaginal Gels on the Integrity and Inflammatory State of the Vaginal Epithelium in vitro
title_sort impact of over-the-counter lactic acid containing vaginal gels on the integrity and inflammatory state of the vaginal epithelium in vitro
topic Reproductive Health
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580709/
https://www.ncbi.nlm.nih.gov/pubmed/36303665
http://dx.doi.org/10.3389/frph.2022.915948
work_keys_str_mv AT tyssendavid theimpactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT hearpsannac theimpactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT gunturkalyani theimpactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT massonlindi theimpactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT cooksimon theimpactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT moultonsimone theimpactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT raveljacques theimpactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT bradshawcatrionas theimpactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT ayehunieseyoum theimpactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT tachedjiangilda theimpactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT tyssendavid impactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT hearpsannac impactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT gunturkalyani impactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT massonlindi impactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT cooksimon impactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT moultonsimone impactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT raveljacques impactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT bradshawcatrionas impactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT ayehunieseyoum impactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro
AT tachedjiangilda impactofoverthecounterlacticacidcontainingvaginalgelsontheintegrityandinflammatorystateofthevaginalepitheliuminvitro