Mention the term microbiome, and most people will quickly think of the gut, probiotics and maybe even fecal microbial transplantation. But it actually refers to the all of the genetic material found in the microbes that live on and in the human body, including yeasts, bacteria and viruses. The vagina has a microbiome, too—even if research on it is lagging behind that done on the microbiomes of other parts of the body.
Progress in this area may soon speed up, however, because on Wednesday, researchers at the University of Maryland School of Medicine announced a new tool that maps the vaginal microbiome with unprecedented resolution. Named VIRGO (which stands for Human Vaginal Non-redundant Gene Catalog), it is the culmination of data collected from many different studies conducted over the past decade. The tool includes the sequences of roughly one million genes in bacteria, viruses and fungi that are active in the vagina.
“The effort will be important for accelerating discoveries into new diagnostic tests and treatments [for vaginal health conditions],” says Jennifer Fettweis, a microbiologist and director of the Vaginal Human Microbiome Project at Virginia Commonwealth University. Fettweis, who was not involved with the new study, explains that the publicly available VIRGO database will help accelerate progress in the field. “I think what [the paper’s authors have] done here is really important on that front,” she says.
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Research efforts over the past decade, including the Human Microbiome Project, have illuminated the extent to which microbes inhabit our bodies. Current estimates show that there are roughly the same number of bacterial cells in the body as human cells.
And these bacterial cells are not just passively sitting around. In the gut, microbes are involved in a variety of essential operations, such as digestion, immune system function and even the production of vitamins. Scientists believe microbes play equally important roles in the vagina but have not yet been able to elucidate their functions. Many hope VIRGO will change that situation.
The tool was assembled by combining metagenomic data from 264 vaginal swab samples obtained by the University of Maryland team with the full genome sequences of 308 vaginal bacterial strains. The samples were sequenced using metagenomic techniques, which allowed scientists to identify the microbial composition, and metatranscriptomic ones, which provided information on what genes were active. The result is a database with more than a million bacterial genes that represent 300 different species present in the vagina.
In one of the earliest examples of its applications, scientists showed how VIRGO can be used to understand the mechanism of an intractable vaginal disorder. During the study, one woman developed a case of bacterial vaginosis—a disorder caused by the overgrowth of harmful bacteria that causes uncomfortable symptoms and, sometimes, serious complications, including preterm birth and infertility.
Using data collected from the woman’s vaginal samples at different points of time throughout the infection, the researchers were able to map out exactly how bacterial gene activity fluctuated during its course. Just before symptoms started, there was an increase in the activity of a bacterial species called Lactobacillus iners
. This species comprised only 1 percent of the microbial community, but it was extremely active, producing 20 percent of the gene products present in the sample. Even though this observation was just based on a single patient, L. iners has previously been associated with bacterial vaginosis in larger studies. It was the first time the microbe’s activity was shown to increase prior to the development of symptoms, however.
“This was a major finding,” says Jacques Ravel, a microbial genomicist at the University of Maryland School of Medicine and senior author of the study. He explains that VIRGO’s ability to see the functional contributions of microbes, even when they are relatively scarce, is a strength of the tool. Ravel, who is also co-founder of, and chief scientist at, LUCA Biologics—a biotechnology company that works to develop live therapeutics for women’s health—sees potential in using VIRGO to develop diagnostic tests as well.
According to Molly Stout, an obstetrics researcher at Washington University School of Medicine in St. Louis, who was not involved in the study, “[the tool] not only addresses who is there in the [bacterial] community but also what are they doing.” Fettweis agrees. She and her team have been working hard “to fill in the dark matter” on the vaginal microbiome, she says. In 2012 she and her colleagues published a database that catalogued all of the bacteria species present in the vagina. She says VIRGO adds a deeper level of resolution that can distinguish strains within a species.
To understand why it is important to identify bacterial strains, consider the common species Escherichia coli. It has hundreds of strains. Many of them live in the intestines of humans and animals and are considered healthy, with some aiding in food digestion. But many others—at least 200—are pathogenic, causing foodborne illnesses and diarrhea, urinary tract infections and even some forms of meningitis.
Individual strains could mean the difference between health and disease in the vagina as well. Lactobacillus crispatus has long been considered the hallmark of a healthy vagina because of its role in producing lactic acid, which maintains a protective acidic environment. But with the help of VIRGO, scientists saw, for the first time, that not all L. crispatus strains are the same—there was enormous diversity in gene expression among them.
“What this implies is that L. crispatus in one woman is very different from L. crispatus in another,” Ravel says. This finding could shake up current efforts that involve designing probiotics based on the bacterial sequence. Ravel explains that each strain can have a different function, and that this idea is a “completely new way of viewing the vaginal microbiome.”
Fettweis hopes databases such as VIRGO will help pave the future path for women’s health. As more and more groups build catalogues and make their data publicly available, she thinks the progress on the vaginal microbiome will accelerate. “The ultimate goal would be to pool all of [the information] together,” she says.