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Study Highlights Diversity, Dynamics of Human Vaginal Microbiome

NEW YORK (GenomeWeb News) – The community of microbes found in the vagina varies dramatically over time in some women but remains relatively stable in others, according to a study appearing online today in Science Translational Medicine.

"We found that the type and the abundance of microbes that are found in the vagina vary over short time intervals in some women and in others they tend to not change," corresponding author Jacques Ravel, a University of Maryland microbiology and immunology researcher and associate director of the University of Maryland's Institute for Genome Sciences, said during a telephone press briefing today.

Ravel and colleagues from the Universities of Maryland and Idaho used 16S ribosomal RNA sequencing to look at the bacterial components of vaginal microbe communities in almost three-dozen women over about four months. Their results indicate that the composition and stability of vaginal microbial communities vary between individuals, with shifts between certain vaginal microbe community types occurring more often than others.

"What we really observed is something of a personalized, temporal dynamic of change in the microbes in each of the women," Ravel said, noting that both menstrual cycle changes and sexual activity tended to contribute to the shifts detected in microbial communities in the vagina.

"Different women have different kinds of communities of microbes and different women have different changes over time," Ravel added.

By understanding these dynamics and variability, the team hopes to eventually come up with more personalized strategies for maintaining vaginal health, predicting infection risk, and treating infections when they do occur.

"We're going to need to start rethinking women's health and treatment," Ravel told reporters.

"The idea would be to group women based on their vaginal microbiome — based on both the kinds of microbes and how those microbes are changing over time," he said. "Then you're going to be able to develop and devise strategies for the treatment of disease, for example, that will be adapted to restoring the microbiota as it was prior to the disease."

In recent years, though, researchers have become increasing interested in trying to make out the components of typical microbial communities at various sites in and on the human body in an effort to understand how these communities affect health and disease.

"Without a complete understanding of the relationships that exist between our human genome and the microbial genomes that inhabit our body, it's going to be impossible to obtain a complete picture of our biology and translate this to better treatment and diagnosis," Ravel told reporters.

In the vagina, for instance, it has long been suspected that lactic acid-producing bacteria, particularly those in the Lactobacillus genera, help to maintain a slightly acidic vaginal environment that wards off potential pathogens such as those causing bacterial vaginosis or other infections.

Nevertheless, the prevalence of Lactobacillus bacteria in the vaginal microbe communities seems to vary from one woman to another and between women from different ethnic backgrounds, according to a Proceedings of the National Academy of Sciences study published in 2010.

For that study, Ravel and collaborators from the University of Maryland, University of Idaho, Emory University, and Proctor and Gamble identified five main vaginal microbe community types using samples from hundreds of North American women.

Some of these communities seemed to be more common in Caucasian and Asian women, while others turned up more frequently in African-American and Hispanic women, Ravel explained, hinting that host genetics might, in part, influence which microbial communities take up residence in the vagina.

For their newest study, researchers looked more closely at the stability of the five vaginal microbiome community types over time in healthy women.

The effort, funded through the National Institutes of Health's Human Microbiome Project, was the first stage of a demonstration project aimed at exploring relationships between vaginal microbiome changes and infection or disease risk.

"We need to develop an accurate understanding of the composition as well as the ecology … of the vaginal microbial ecosystem in normal, healthy women," Ravel explained. "It's really an essential pre-requisite for comprehending how the normal microbiota might be able to reduce the risk of acquiring, for example, communicable diseases or for defining the factors that determine disease susceptibility."

Using 16S rRNA data generated on the Roche 454 Titanium sequencing platform, the researchers characterized the types and abundance of bacteria in vaginal samples that had been self-collected twice per week for 16 weeks by 32 healthy women.

They also folded in metabolomic data on samples from a subset of the women, as well as daily, self-reported information on menstrual cycle stage, sexual activity, hygiene, and other factors suspected to influence the nature or abundance of microbes in the vagina.

From the thousands of 16S rRNA sequences generated for each sample, the team again saw five main vaginal microbiome community types, including three community types where Lactobacillus species dominated. The remaining two community types were more heterogeneous and contained lower Lactobacillus levels. Again, these community types appeared to vary somewhat with ethnicity.

Although microbiome community dynamics were fairly distinct from one woman to the next, the team was able to discern five broad transition patterns involving the five main vaginal bacterial community types, with certain community types regularly giving way to specific, alternative communities.

Some of these community types also tended to be more stable than others, they found, particularly those with high levels of lactic-acid producing L. crispatus or L. gasseri bacteria. Likewise, the team also saw large, menstruation-related changes in vaginal microbiome stability in some of the women, but not others.

"Fluctuations in community composition and constancy are mainly affected by time in the menstrual cycle, community class, and, to a certain extent, by sexual activity," study authors noted, "but other unknown factors are also certainly at play."

Given the levels of diversity and variability found in the vaginal microbiomes, coupled with the health of the study participants, authors of the study noted that low levels of Lactobacillus bacteria, elevated diversity, and enhanced variability in the vaginal microbiome may not be indicative of higher infection risk, as previously suspected.

"The new findings clearly reveal that the vaginal microbiome is much more heterogeneous and fluctuating than previously believed and, most importantly, that multiple bacterial communities with variable compositions and stability are present in reproductive-age women who do not exhibit any clinical genital tract symptoms," Weill Cornell Medical College immunology and infectious disease researchers Steven Witkin and William Ledger wrote in an accompanying editorial.

Moreover, the pair noted that the study "signals the death knell of the still widely accepted statement that healthy vaginal communities must contain a high proportion of Lactobacilli."

As part of their ongoing effort to determine which vaginal microbiome features are key to health and disease, Ravel and his team have already enrolled around 100 to 150 additional women for the second phase of their study — a prospective, longitudinal analyses of vaginal swabs collected daily from healthy women and women who developed bacterial vaginosis at some point over the course of the study.

"We have a certain number of women who experienced bacterial vaginosis, but we also have all of the samples that were collected the days prior to the diagnosis by a clinician," Ravel explained. "We can actually, now, get to causality by looking at behaviors and biological samples from women prior to the condition occurring."

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