Biomarker: Institute for Genomic Biology December 2008

People don’t always like to be reminded of it, but microbes are everywhere. There are more microbes on one human hand than there are humans in the world. The vast majority of these organisms are benign, and many are even beneficial: they help us breathe and digest our food; they contribute to the development of our immune systems and impact the effectiveness of drugs we take. Still, as anyone who has had food poisoning or a sexually transmitted disease knows, sometimes microbes can really be unwelcome “houseguests.”

Brenda Wilson, University of Illinois professor of microbiology and leader of the newly formed Host-Microbe Systems (HMS) theme at the IGB, has dedicated her career to understanding the impact of some of the most pathogenic microbes on their hosts. Under her leadership, research in the HMS theme has focused on studying the dynamics between humans and animals and the microbes—both benign and pathogenic—that live inside them.

“Our prior exposure to particular natural pressures like microbes greatly shapes our responses to subsequent exposure to the same or similar microbes, so it is important for us to understand the role that our normal microbiota play in maintaining health,” says Wilson. “But in order to do that, we need to know which microbes or groups of microbes are important contributors and which are not. One way to determine this is to compare our microbiota with those of other closely related species—nonhuman primates, in other words.”

Wilson’s group has chosen to focus foremost on the vaginal ecology of both human and nonhuman primates. Investigators have long recognized the need to know how microbes might interact synergistically to cause infection or otherwise affect the host ecosystem. While many researchers are already looking at the gut and the oral cavity to understand those interactions, members of the HMS theme are among the first to investigate the vaginal system.

And there is much we don’t know. For example, what microbes are normally in the vagina and what happens when that population changes? What makes a vaginal environment healthy or diseased? Are more promiscuous animals more susceptible to sexually transmitted diseases, or do they evolve resistance? In addition to answering these questions, the researchers seek to identify the difference between microbes associated with healthy, full-term pregnancies and those associated with preterm births. They also want to discover how certain microbes impact the fertility and overall health of endangered primates, not to mention humans, says Wilson.

This research will also be the first time that scientists have used molecular genomic techniques to grasp the full complexity of the vaginal microbiome and see which microbes are harmful, which are beneficial, and which are simply benign. Another exciting aspect of the theme is that it brings together scientists who don’t normally work together, including faculty from microbiology, animal sciences, anthropology, and computer science—as well as many other departments. This kind of interdisciplinary collaboration is, of course, central to the IGB’s mission.

“This project has enabled to me branch out into a whole new field,” says Wilson, whose main area of research is bacterial toxins and understanding how they interact with host cells so that she can develop an effective post-exposure antitoxin. “There are lots of different folks coming together to work on something we all think is very important. It allows us to be interdisciplinary,” she adds. “We couldn’t do this work if we were each in our own little world.”

Recently Wilson and Abigail Salyers, both microbiologists, along with Rebecca Stumpf and Steven Leigh, both anthropologists, received a three-year, $300,000 grant from NSF for a comparative study of the vaginal ecology of nonhuman primates. This ambitious and ground-breaking project will collect data for at least 15 species of nonhuman primates. And there’s a lot of data to gather: “We have absolutely no idea really about the vaginal microbial community,” says Wilson, explaining why they chose this subject. This project will expand on the ongoing human vaginal health project, where they and the other HMS theme researchers have been exploring the role of the vaginal microbial ecosystem on bacterial vaginosis and human health.

This collaboration represents an exciting new direction for anthropologists, who have long looked at the macro-environment to learn how it impacts animal/human morphology, behavior, and genetics. But rarely have they examined the micro-environment and its impact on primate behavior, fertility, and genetics. In this project, anthropologists can consider how all primates—both human and nonhuman—interact with and are shaped by their microbial populations.

Stumpf and Leigh have developed several hypotheses regarding variation in primate vaginal microbiota, designed much of the species comparisons, and coordinated the collection of the primate samples. This study will compare humans with ring-tailed lemurs, sifakas, marmosets, howler monkeys, titi monkeys, vervets, macaques, baboons, colobus monkeys, chimpanzees, and bonobos. Samples will be collected by field researchers who are already studying these primates for other reasons. While some primates in the study will be captive, the vast majority will be wild; it’s an important distinction, since the microbiota of captive and wild animals vary significantly.

Gathering baseline data about the vaginal biome is the first step towards understanding the role of microbes—a role made more complex by the fact that they can affect their host alone or through interactions other microbes. For example, perhaps in some cases a certain microbe is benign until it is joined by a second microbe, at which point the two microbes together can cause vaginal infection. In addition, just as some male primates have elements in their seminal fluid that may harm females or influence the timing of ovulation, female host-microbe interactions could have evolved to either inhibit or facilitate sperm transport.

“By examining sexual dynamics and dialectics at a microbial level, this research opens the door to new perspectives in understanding sexual selection,” says Stumpf.

Taking a census of microbes in the nonhuman primate population is a complex research task because there is a wide diversity of microbes even within a single species. The team’s first goal is to fully document that variation, as well as the variation between species, and determine what factors (such as taxonomy, sexual practices, group size, and body size) influence that variation. And even one animal’s samples can fluctuate because the menstrual cycle affects microbial community composition, and the vaginal biome changes depending on whether or not the animal is menstruating or pregnant.

There already have been some surprises in HMS research. Until now, scientists thought that the baboon’s reproductive system was a good model for the human’s because its menstrual cycle and estrogen and progesterone levels were very similar to the human’s. Wilson and her colleagues, however, have found that that is not the case. Neither the captive baboon’s vaginal biome nor the wild baboon’s is at all the same as the human’s. In addition, the microbial populations of captive and wild baboons are very different from one another.

“So the baboon is not a good model for the human and we are setting out to gather other primate samples,” says Wilson.

The group is also dealing directly with human microbial communities in collaboration with the J. Craig Venter Institute (JCVI) on the Human Microbiome Project, which seeks to catalog all microbes co-existing with humans on the skin, in the oral cavity, and in the vaginal tract. IGB microbiologists will identify and sequence microbes in the vagina for the Human Microbiome Project, and are also collaborating with Carle and Christie clinics and the University of Illinois at Chicago School of Medicine to collect human vaginal samples. All this research promises to yield far-reaching results, gathering data that will provide information about human reproductive health as well as the fertility of endangered primate populations.

“Pathological vaginal microbes are implicated in human preterm birth and pregnancy complications,” says Stumpf. “By providing more insight into the factors influencing variation in microbial community composition, we hope to contribute to improving women’s health.”