Blog created by: Michelle Wright, Jennifer Fettweis, Hope Wolfe, Jerome Strauss, Gregory Buck, & Timothy York. 

The vaginal microbiome can be protective or damaging to a woman’s health. Research teams across the globe report common microbial communities within the vaginal niche, many comprised of high proportions of Lactobacillus. However, it is not known why some women harbor bacterial communities that are more likely to prevent adverse gynecologic and reproductive outcomes, including those with a high proportion of Lactobacillus crispatus.

Previous work identified health behaviors and environmental factors that influence the type of bacteria present in vaginal microbial communities, such as oral contraceptive use and hygiene practices.^1-4 While these studies clarified some of the factors associated with differences and changes in vaginal microbiome composition, we still didn’t have a full explanation for why some women harbor high proportions of protective Lactobacillus. 

To investigate if host genetics could be contributing to which types of microbes colonize the vaginal niche, we compared the vaginal microbiomes of identical and non-identical twin pairs. We found that the likelihood of harboring L. crispatus, is influenced by the host genes, particularly among women of European ancestry.

The Power of Twins

 Analyzing the microbiome among identical and non-identical twin pairs permits determination of the relative influence of the environment and genetics on which microbes we harbor. Traditional genome-wide association studies (GWAS) can identify associations between traits and specific genetic variants. However, GWAS can be costly and often futile in the absence of evidence of a genetic influence. Therefore, a logical first step is to determine if a given trait, in our case predominant vaginal microbes, are heritable. These analyses can be completed without costly genomic analysis of large numbers of individuals. Identical twins share 100% of their genes and non-identical twins share roughly 50% of their genes. Therefore, if identical twins are more similar for a trait that non-identical twins, this provides some evidence that the trait is influenced by our genes.

 Genetic Preference for Microbes

 The vaginal microbiome is unique in that low diversity is associated with vaginal health. Lower diversity is generally associated with Lactobacillus colonization, and it is not uncommon for one species to constitute a large proportion (over 90% in some women) of the bacteria identified in the vagina. High proportions of Lactobacillus, notably L. crisptaus, is associated with increased protection from sexually transmitted infection and lower risk of preterm birth. In our study, we determined that heritability of L. crispatus carriage is nearly 35%, which is similar to what Si and colleagues reported among Korean women.⁶ This is similar in magnitude of heritability observed for other human traits (average = 49%), including reproductive traits (average 44%).⁵ The current study argues that genetics influences the vaginal microbiome composition, and in particular, that L. crispatus is genetically favored in women of European ancestry.

Figure created with BioRender.com

 Why this Matters

 Among vaginal microbiome studies, none show the presence of vaginal L. crispatus in all women. Most find well under 40% of women harboring a L. crispatus as the dominant microbe in the vaginal community, depending on the population and reason for the study. Yet, L. crispatus predominance is often held as the gold standard microbe for vaginal health. Interventions or probiotics developed in order to shift the vaginal microbiome to a L. crispatus state may not be as effective for some women due to their genetic make-up. As shown in our study, heritability may explain why L. crispatus is more prevalent among some women and not others. Personalized approaches may be needed to ensure vaginal health for all women, such as identifying protective features of other vaginal microbiome communities.

The full study can be read here.

 References

1. Gajer, P. et al. Temporal dynamics of the human vaginal microbiota. Sci Transl Med 4, 132ra52 (2012).
2. Marrazzo, J. M. et al. Extravaginal Reservoirs of Vaginal Bacteria as Risk Factors for Incident Bacterial Vaginosis. J. Infect. Dis. 205, 1580–1588 (2012).
3. Brooks, J. P. et al. Effects of combined oral contraceptives, depot medroxyprogesterone acetate and the levonorgestrel-releasing intrauterine system on the vaginal microbiome. Contraception 95, 405–413 (2017).
4. Brooks, J. P. et al. Changes in vaginal community state types reflect major shifts in the microbiome. Microb. Ecol. Health Dis. 28, 1303265 (2017).
5. Polderman, T. J. C. et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat. Genet. 47, 702–709 (2015).
6. Si, J., You, H. J., Yu, J., Sung, J. & Ko, G. P. 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).