Lactic acid from vaginal microbiota enhances cervicovaginal epithelial barrier integrity by promoting tight junction protein expression

阴道微生物群中的乳酸通过促进紧密连接蛋白的表达来增强宫颈阴道上皮屏障的完整性

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作者:David Jose Delgado-Diaz #, Brianna Jesaveluk #, Joshua A Hayward, David Tyssen, Arghavan Alisoltani, Matthys Potgieter, Liam Bell, Elizabeth Ross, Arash Iranzadeh, Imane Allali, Smritee Dabee, Shaun Barnabas, Hoyam Gamieldien, Jonathan M Blackburn, Nicola Mulder, Steven B Smith, Vonetta L Edwards, A

Background

Women with a cervicovaginal microbiota dominated by Lactobacillus spp. are at reduced risk of acquiring sexually transmitted infections including HIV, but the biological mechanisms involved remain poorly defined. Here, we performed metaproteomics on vaginal swab samples from young South African women (n = 113) and transcriptomics analysis of cervicovaginal epithelial cell cultures to examine the ability of lactic acid, a metabolite produced by cervicovaginal lactobacilli, to modulate genital epithelial barrier function.

Conclusions

These findings reveal a novel ability of vaginal lactic acid to enhance genital epithelial barrier integrity that may help prevent invasion by sexually transmitted pathogens. Video abstract.

Results

Compared to women with Lactobacillus-depleted microbiota, women dominated by vaginal lactobacilli exhibit higher abundance of bacterial lactate dehydrogenase, a key enzyme responsible for lactic acid production, which is independently associated with an increased abundance of epithelial barrier proteins. Physiological concentrations of lactic acid enhance epithelial cell culture barrier integrity and increase intercellular junctional molecule expression. Conclusions: These findings reveal a novel ability of vaginal lactic acid to enhance genital epithelial barrier integrity that may help prevent invasion by sexually transmitted pathogens. Video abstract.

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