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      Beyond bacterial vaginosis: vaginal lactobacilli and HIV risk

      review-article
      1 , , 1 , 2
      Microbiome
      BioMed Central
      Vaginal microbiota, HIV, immunology, bacterial vaginosis, Lactobacillus

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          Abstract

          HIV incidence continues to be unacceptably high in Eastern and Southern Africa, with women disproportionately affected. An increased per-contact risk of HIV acquisition among African, Caribbean, and other Black (ACB) women has been associated with the higher prevalence of bacterial vaginosis (BV) in these communities, wherein the vaginal microbiota is predominated by diverse pro-inflammatory anaerobic bacteria. However, while the vaginal microbiota in BV-free women is typically predominated by one of several different Lactobacillus spp., the degree of HIV protection afforded by a Lactobacillus-predominant vaginal microbiota also varies considerably. Specifically, L. crispatus is associated with an immunoregulatory genital immune environment, exclusion of BV-associated bacteria, and reduced HIV risk. In contrast, less HIV protection or exclusion of BV-associated bacteria and fewer immune benefits have been associated with L. iners—which is unfortunately the most common Lactobacillus species among ACB women. These species-specific clinical differences are underpinned by substantial genomic differences between Lactobacillus species: for instance, the much smaller genome of L. iners lacks the coding sequence for D-lactic acid dehydrogenase and cannot produce the D-lactate isomer that enhances HIV trapping in mucus but encodes for epithelial cell toxins and stress resistance proteins that may enhance bacterial survival in the context of microbiota and environmental fluctuations. While more studies are needed to elucidate whether differences in HIV protection between Lactobacillus species are due to direct genital immune effects or the exclusion of proinflammatory BV-associated bacteria, the current body of work suggests that for BV treatment to succeed as an HIV prevention strategy, it may be necessary to induce a vaginal microbiota that is predominated by specific (non -iners) Lactobacillus species.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s40168-021-01183-x.

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          Most cited references40

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          Vaginal microbiome of reproductive-age women.

          The means by which vaginal microbiomes help prevent urogenital diseases in women and maintain health are poorly understood. To gain insight into this, the vaginal bacterial communities of 396 asymptomatic North American women who represented four ethnic groups (white, black, Hispanic, and Asian) were sampled and the species composition characterized by pyrosequencing of barcoded 16S rRNA genes. The communities clustered into five groups: four were dominated by Lactobacillus iners, L. crispatus, L. gasseri, or L. jensenii, whereas the fifth had lower proportions of lactic acid bacteria and higher proportions of strictly anaerobic organisms, indicating that a potential key ecological function, the production of lactic acid, seems to be conserved in all communities. The proportions of each community group varied among the four ethnic groups, and these differences were statistically significant [χ(2)(10) = 36.8, P < 0.0001]. Moreover, the vaginal pH of women in different ethnic groups also differed and was higher in Hispanic (pH 5.0 ± 0.59) and black (pH 4.7 ± 1.04) women as compared with Asian (pH 4.4 ± 0.59) and white (pH 4.2 ± 0.3) women. Phylotypes with correlated relative abundances were found in all communities, and these patterns were associated with either high or low Nugent scores, which are used as a factor for the diagnosis of bacterial vaginosis. The inherent differences within and between women in different ethnic groups strongly argues for a more refined definition of the kinds of bacterial communities normally found in healthy women and the need to appreciate differences between individuals so they can be taken into account in risk assessment and disease diagnosis.
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            Role of the gut microbiota in nutrition and health

            Ana M Valdes and colleagues discuss strategies for modulating the gut microbiota through diet and probiotics
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              Temporal dynamics of the human vaginal microbiota.

              Elucidating the factors that impinge on the stability of bacterial communities in the vagina may help in predicting the risk of diseases that affect women's health. Here, we describe the temporal dynamics of the composition of vaginal bacterial communities in 32 reproductive-age women over a 16-week period. The analysis revealed the dynamics of five major classes of bacterial communities and showed that some communities change markedly over short time periods, whereas others are relatively stable. Modeling community stability using new quantitative measures indicates that deviation from stability correlates with time in the menstrual cycle, bacterial community composition, and sexual activity. The women studied are healthy; thus, it appears that neither variation in community composition per se nor higher levels of observed diversity (co-dominance) are necessarily indicative of dysbiosis.
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                Author and article information

                Contributors
                ericm.armstrong@mail.utoronto.ca
                Journal
                Microbiome
                Microbiome
                Microbiome
                BioMed Central (London )
                2049-2618
                10 December 2021
                10 December 2021
                2021
                : 9
                : 239
                Affiliations
                [1 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Department of Medicine, , University of Toronto, ; Toronto, Canada
                [2 ]GRID grid.417184.f, ISNI 0000 0001 0661 1177, University Health Network, Toronto General Hospital, Immunodeficiency Clinic, ; Toronto, Canada
                Author information
                http://orcid.org/0000-0002-4530-6631
                Article
                1183
                10.1186/s40168-021-01183-x
                8665571
                34893070
                467458f0-ae33-4ca8-9d79-d5366414c65d
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 30 September 2021
                : 1 November 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000024, Canadian Institutes of Health Research;
                Award ID: PJT-156123
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2021

                vaginal microbiota,hiv,immunology,bacterial vaginosis,lactobacillus

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