Huttenhower, C. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012).
Nugent, R. P., Krohn, M. A. & Hillier, S. L. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol 29, 297–301 (1991).
Amsel, R. et al. Nonspecific vaginitis: diagnostic criteria and microbial and epidemiologic associations. Am. J. Med. 74, 14–22 (1983).
Boris, S. & Barbes, C. Role played by lactobacilli in controlling the population of vaginal pathogens. Microbes Infect 2, 543–546 (2000).
Tyssen, D. et al. Anti-HIV-1 Activity of Lactic Acid in Human Cervicovaginal Fluid. mSphere 3, e00055–00018 (2018).
Petrova, M. I., Reid, G., Vaneechoutte, M. & Lebeer, S. Lactobacillus iners: friend or foe?. Trends Microbiol. 25, 182–191 (2017).
Schwebke, J. R. & Desmond, R. Natural history of asymptomatic bacterial vaginosis in a high-risk group of women. Sex. Transm. Dis. 34, 876–877 (2007).
Larsson, P.-G., Platz-Christensen, J.-J., Thejls, H., Forsum, U. & Påhlson, C. Incidence of pelvic inflammatory disease after first-trimester legal abortion in women with bacterial vaginosis after treatment with metronidazole: a double-blind, randomized study. Am. J. Obstet. Gynecol. 166, 100–103 (1992).
Hillier, S. L. et al. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. N. Engl. J. Med. 333, 1737–1742 (1995).
Donders, G. et al. Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy. BJOG 116, 1315–1324 (2009).
Borgdorff, H. et al. Lactobacillus-dominated cervicovaginal microbiota associated with reduced HIV/STI prevalence and genital HIV viral load in African women. ISME J. 8, 1781 (2014).
Cherpes, T. L., Hillier, S. L., Meyn, L. A., Busch, J. L. & Krohn, M. A. A delicate balance: risk factors for acquisition of bacterial vaginosis include sexual activity, absence of hydrogen peroxide-producing lactobacilli, black race, and positive herpes simplex virus type 2 serology. Sex. Transm. Dis. 35, 78–83 (2008).
Dareng, E. O. et al. Prevalent high-risk HPV infection and vaginal microbiota in Nigerian women. Epidemiol. Infect. 144, 123–137 (2016).
Brotman, R. M. et al. Interplay between the temporal dynamics of the vaginal microbiota and human papillomavirus detection. J. Infect. Dis. 210, 1723–1733 (2014).
Lee, J. E. et al. Association of the vaginal microbiota with human papillomavirus infection in a Korean twin cohort. PLoS ONE 8, e63514–e63514 (2013).
Rodriguez-Cerdeira, C., Sanchez-Blanco, E. & Alba, A. Evaluation of association between vaginal infections and high-risk human papillomavirus types in female sex workers in Spain. ISRN Obstet. Gynecol. https://doi.org/10.5402/2012/240190 (2012).
Di Paola, M. et al. Characterization of cervico-vaginal microbiota in women developing persistent high-risk Human Papillomavirus infection. Sci. Rep. 7, 10200 (2017).
Cauci, S. Vaginal immunity in bacterial vaginosis. Curr. Infect. Dis. Rep. 6, 450–456 (2004).
Stokholm, J. et al. Antibiotic use during pregnancy alters the commensal vaginal microbiota. Clin. Microbiol. Infect. 20, 629–635 (2014).
Welch, J. S. Quantitative and qualitative effects of douche preparations on vaginal microflora. Obstet. Gynecol. 81, 320–321 (1993).
Brotman, R. M. et al. The effect of vaginal douching cessation on bacterial vaginosis: a pilot study. Am. J. Obstet. Gynecol. 198(628), e621-628 (2008).
Schwebke, J. R., Richey, C. M. & Weiss, H. L. Correlation of behaviors with microbiological changes in vaginal flora. J. Infect. Dis. 180, 1632–1636 (1999).
Beigi, R. H., Wiesenfeld, H. C., Hillier, S. L., Straw, T. & Krohn, M. A. Factors associated with absence of H2O2-producing Lactobacillus among women with bacterial vaginosis. J. Infect. Dis. 191, 924–929 (2005).
Ahluwalia, N. & Grandjean, H. Nutrition, an under-recognized factor in bacterial vaginosis. J. Nutr. 137, 1997–1998 (2007).
Neggers, Y. H. et al. Dietary intake of selected nutrients affects bacterial vaginosis in women. J. Nutr. 137, 2128–2133 (2007).
Brotman, R. M. et al. Association between cigarette smoking and the vaginal microbiota: a pilot study. BMC Infect. Dis. 14, 471 (2014).
van Houdt, R. et al. Lactobacillus iners-dominated vaginal microbiota is associated with increased susceptibility to Chlamydia trachomatis infection in Dutch women: a case–control study. Sex. Transm. Infect. 94, 117–123 (2017).
Noyes, N., Cho, K.-C., Ravel, J., Forney, L. J. & Abdo, Z. Associations between sexual habits, menstrual hygiene practices, demographics and the vaginal microbiome as revealed by Bayesian network analysis. PLoS ONE 13, e0191625 (2018).
Ravel, J. et al. Vaginal microbiome of reproductive-age women. Proc. Natl. Acad. Sci. USA 108(Suppl 1), 4680–4687 (2011).
Zhou, X. et al. Differences in the composition of vaginal microbial communities found in healthy Caucasian and black women. ISME J. 1, 121–133 (2007).
Zhou, X. et al. The vaginal bacterial communities of Japanese women resemble those of women in other racial groups. FEMS Immunol. Med. Microbiol. 58, 169–181 (2010).
Borgdorff, H. et al. The association between ethnicity and vaginal microbiota composition in Amsterdam, the Netherlands. PLoS ONE 12, e0181135 (2017).
Verstraelen, H. et al. Characterisation of the human uterine microbiome in non-pregnant women through deep sequencing of the V1–2 region of the 16S rRNA gene. PeerJ 4, e1602 (2016).
Rick, A.-M. et al. Open forum infectious diseases. (Oxford University Press, Oxford).
Anukam, K. C., Osazuwa, E. O., Ahonkhai, I. & Reid, G. Lactobacillus vaginal microbiota of women attending a reproductive health care service in Benin city, Nigeria. Sex. Transm. Dis. 33, 59–62 (2006).
Bourgeon, L., Burke, A. & Higham, T. Earliest human presence in North America Dated to the Last Glacial Maximum: new radiocarbon dates from Bluefish Caves, Canada. PLoS ONE 12, e0169486 (2017).
Bortolini, M. C. et al. Y-chromosome evidence for differing ancient demographic histories in the Americas. Am. J. Hum. Genet. 73, 524–539 (2003).
Hurtado, A. M., Hurtado, I. & Hill, K. Public health and adaptive immunity among natives of South America. Lost Paradises and the Ethics of Research and Publication 164–192 (Oxford University Press, New York, 2003).
Lindenau, J. et al. Distribution patterns of variability for 18 immune system genes in Amerindians–relationship with history and epidemiology. HLA 82, 177–185 (2013).
Bhatia, K. K., Black, F. L., Smith, T. A., Prasad, M. L. & Koki, G. N. Class I HLA antigens in two long-separated populations: Melanesians and South Amerinds. Am. J. Phys. Anthropol. 97, 291–305 (1995).
Watkins, D. I. et al. New recombinant HLA-B alleles in a tribe of South American Amerindians indicate rapid evolution of MHC class I loci. Nature 357, 329–333 (1992).
Ewerton, P. D., de Meira Leite, M., Magalhães, M., Sena, L. & dos Santos, E. J. M. Amazonian Amerindians exhibit high variability of KIR profiles. Immunogenetics 59, 625–630 (2007).
Freire, G. & Tillett, A. Salud indígena en Venezuela. First volume. (Dirección de Salud Indígena, 2007).
Contreras, M. et al. The bacterial microbiota in the oral mucosa of rural Amerindians. Microbiology 156, 3282–3287 (2010).
Clemente, J. C. et al. The microbiome of uncontacted Amerindians. Sci. Adv. 1, e1500183 (2015).
Blaser, M. J. et al. Distinct cutaneous bacterial assemblages in a sampling of South American Amerindians and US residents. ISME J. 7, 86–95 (2012).
Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature 486, 222–222 (2012).
Godinho, N. M. D. O. O Impacto das Migrações na Constituição Genética de Populações Latino-Americanas. (2008).
Jespers, V. et al. The significance of Lactobacillus crispatus and L. vaginalis for vaginal health and the negative effect of recent sex: a cross-sectional descriptive study across groups of African women. BMC Infect. Dis. 15, 115 (2015).
Gosmann, C. et al. Lactobacillus-deficient cervicovaginal bacterial communities are associated with increased HIV acquisition in Young South African Women. Immunity 46, 29–37 (2017).
Godoy-Vitorino, F. et al. Cervicovaginal fungi and bacteria associated with cervical intraepithelial neoplasia and high-risk Human Papillomavirus infections in a Hispanic population. Front. Microbiol. 9, 2533 (2018).
Tarnberg, M., Jakobsson, T., Jonasson, J. & Forsum, U. Identification of randomly selected colonies of lactobacilli from normal vaginal fluid by pyrosequencing of the 16S rDNA variable V1 and V3 regions. APMIS 110, 802–810 (2002).
Huse, S. M., Ye, Y., Zhou, Y. & Fodor, A. A. A core human microbiome as viewed through 16S rRNA sequence clusters. PLoS ONE 7, e34242 (2012).
Shen, J. et al. Effects of low dose estrogen therapy on the vaginal microbiomes of women with atrophic vaginitis. Sci. Rep. 6, 24380 (2016).
Witkin, S. S. et al. Vaginal biomarkers that predict cervical length and dominant bacteria in the vaginal microbiomes of pregnant women. mBio 10, e02242-129 (2019).
Ravel, J. et al. Daily temporal dynamics of vaginal microbiota before, during and after episodes of bacterial vaginosis. Microbiome 1, 29 (2013).
Smith, B. C. et al. The cervical microbiome over 7 years and a comparison of methodologies for its characterization. PLoS ONE 7, e40425 (2012).
Gajer, P. et al. Temporal dynamics of the human vaginal microbiota. Sci. Transl. Med. 4, 132ra152 (2012).
Kim, T. K. et al. Heterogeneity of vaginal microbial communities within individuals. J. Clin. Microbiol. 47, 1181–1189 (2009).
Liu, M.-B. et al. Diverse vaginal microbiomes in reproductive-age women with vulvovaginal candidiasis. PLoS ONE 8, e79812 (2013).
Verstraelen, H. et al. Longitudinal analysis of the vaginal microflora in pregnancy suggests that L. crispatus promotes the stability of the normal vaginal microflora and that L. gasseri and/or L. iners are more conducive to the occurrence of abnormal vaginal microflora. BMC Microbiol. 9, 116 (2009).
Byrne, E. H. et al. Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract. Immunity 42, 965–976 (2015).
Mach, N. & Fuster-Botella, D. Endurance exercise and gut microbiota: a review. J. Sport Health Sci. 6, 179–197 (2017).
Tasnim, N., Abulizi, N., Pither, J., Hart, M. M. & Gibson, D. L. Linking the gut microbial ecosystem with the environment: does gut health depend on where we live?. Front. Microbiol. 8, 1935 (2017).
Collins, M. D. The Prokaryotes 1013–1019 (Springer, Berlin, 2006).
Freitas, A. C. et al. Increased richness and diversity of the vaginal microbiota and spontaneous preterm birth. Microbiome 6, 117 (2018).
Marrazzo, J. M., Thomas, K. K., Fiedler, T. L., Ringwood, K. & Fredricks, D. N. Relationship of specific vaginal bacteria and bacterial vaginosis treatment failure in women who have sex with women. Ann. Intern. Med. 149, 20–28 (2008).
Si, J., You, H. J., Yu, J., Sung, J. & Ko, G. Prevotella as a hub for vaginal microbiota under the influence of host genetics and their association with obesity. Cell Host Microbe 21, 97–105 (2017).
Srinivasan, S. et al. Bacterial communities in women with bacterial vaginosis: high resolution phylogenetic analyses reveal relationships of microbiota to clinical criteria. PLoS ONE 7, e37818 (2012).
Yeoman, C. J. et al. A multi-omic systems-based approach reveals metabolic markers of bacterial vaginosis and insight into the disease. PLoS ONE 8, e56111 (2013).
Oakley, B. B., Fiedler, T. L., Marrazzo, J. M. & Fredricks, D. N. Diversity of human vaginal bacterial communities and associations with clinically defined bacterial vaginosis. Appl. Environ. Microbiol. 74, 4898–4909 (2008).
Machado, A. & Cerca, N. Influence of biofilm formation by gardnerella vaginalis and other anaerobes on bacterial vaginosis. J. Infect. Dis. 212, 1856–1861 (2015).
Vargas-Robles, D. et al. High rate of infection by only oncogenic human papillomavirus in Amerindians. mSphere 3, e00176-e118 (2018).
Song, D., Li, H., Li, H. & Dai, J. Effect of human papillomavirus infection on the immune system and its role in the course of cervical cancer. Oncol. Lett. 10, 600–606 (2015).
Briselden, A. M., Moncla, B. J., Stevens, C. E. & Hillier, S. L. Sialidases (Neuraminidases) in bacterial vaginosis and bacterial vaginosis-associated microflora. J. Clin. Microbiol. 30, 663–666 (1992).
Gillet, E. et al. Bacterial vaginosis is associated with uterine cervical human papillomavirus infection: a meta-analysis. BMC Infect. Dis. 11, 10 (2011).
Discacciati, M. G. et al. Presence of 20% or more clue cells: an accurate criterion for the diagnosis of bacterial vaginosis in Papanicolaou cervical smears. Diagn. Cytopathol. 34, 272–276 (2006).
World Health Organization. Haemoglobin Concentrations for the Diagnosis of Anaemia and Assessment of Severity (World Health Organization, Geneva, 2011).
Magoč, T. & Salzberg, S. L. FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics 27, 2957–2963 (2011).
Callahan, B. J. et al. DADA2: High resolution sample inference from Illumina amplicon data. Nat. Methods 13, 581–583 (2016).
Allard, G., Ryan, F. J., Jeffery, I. B. & Claesson, M. J. SPINGO: a rapid species-classifier for microbial amplicon sequences. BMC Bioinform. 16, 324 (2015).
Cole, J. R. et al. Ribosomal Database Project: data and tools for high throughput rRNA analysis. Nucleic Acids Res. 42, D633–D642 (2013).
Morgulis, A. et al. Database indexing for production MegaBLAST searches. Bioinformatics 24, 1757–1764 (2008).
Muzny, C. A. et al. Characterization of the vaginal microbiota among sexual risk behavior groups of women with bacterial vaginosis. PLoS ONE 8, e80254 (2013).
Caporaso, J. G. et al. QIIME allows analysis of high-throughput community sequencing data. Nat. Methods 7, 335–336 (2010).
R: A language and environment for statistical computing (R Foundation for Statistical Computing, Vienna, Austria, 2016).
Oksanen, J. et al. vegan: Community Ecology Package. R package version 2.4-4. R Development Core Team. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing (2010).
Anderson, M. J. Permutation tests for univariate or multivariate analysis of variance and regression. Can. J. Fish. Aquat. Sci. 58, 626–639 (2001).
Bates, D., Maechler, M., Bolker, B. & Walker, S. Fitting Linear Mixed-Effects Models Using lme4. (2015).
textmineR: Functions for Text Mining and Topic Modeling v. 2.0.6 (2017).
Rousseeuw, P. J. Silhouettes: a graphical aid to the interpretation and validation of cluster analysis. J. Comput. Appl. Math. 20, 53–65 (1987).
Walther, R. T. A. G. Cluster validation by prediction strength. J. Comput. Graph. Stat. 14, 511–528 (2005).
Philentropy: Information Theory and Distance Quantification with R (2018).
Hsieh, T. C., Ma, K. H. & Chao, A. iNEXT: an R package for rarefaction and extrapolation of species diversity (Hill numbers). Methods Ecol Evol 7, 1451–1456 (2016).
Cohen, J. A coefficient of agreement for nominal scales. Educ. Psychol. Meas. 20, 37–46 (1960).
Viera, A. J. & Garrett, J. M. Understanding interobserver agreement: the kappa statistic. Fam. Med. 37, 360–363 (2005).
Segata, N. et al. Metagenomic biomarker discovery and explanation. Genome Biol. 12, R60 (2011).
Nakazawa, M. fmsb: Functions for medical statistics book with some demographic data. R package version 0.4 (2014).
Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. B 57, 289–300 (1995).
Wickham, H. Reshaping Data with the reshape Package. J. Stat. Softw. 21, 1–20 (2007).
gplots: Various R Programming Tools for Plotting Data (R, 2016).
Vázquez-Baeza, Y., Pirrung, M., Gonzalez, A. & Knight, R. EMPeror: a tool for visualizing high-throughput microbial community data. Gigascience 2, 16 (2013).