Review and opinion articles on the vaginal microbiota

We have published two new papers on the vaginal microbiota. The first one is a review written with Steve Smith, who is a talented graduate student in the group working at the interface of biology and computational biology. The review is on the interplay between the vaginal microbiota, the host immune systems and the reproductive physiology. Here is the abstract:

The interaction between the human host and the vaginal microbiota is highly dynamic. Major changes in the vaginal physiology and microbiota over a woman's lifetime are largely shaped by transitional periods such as puberty, menopause, or pregnancy, while daily fluctuations in microbial composition observed through culture-independent studies are more likely the results of daily life activities and behaviours. The vaginal microbiota of reproductive-aged women is largely made up of at least five different community state types. Four of these community state types are dominated by lactic-acid producing Lactobacillus spp. while the fifth is commonly composed of anaerobes and strict anaerobes and is sometimes associated with vaginal symptoms. The production of lactic acid has been associated with contributing to the overall health of the vagina due to its direct and indirect effects on pathogens and host defense. Some species associated with non-Lactobacillus vaginal microbiota may trigger immune responses as well as degrade the host mucosa, processes that ultimately increase susceptibility to infections and contribute to negative reproductive outcomes such as infertility and preterm birth. Further studies are needed to better understand the functional underpinnings of how the vaginal microbiota affect host physiology but also how host physiology affects the vaginal microbiota. Understanding this fine-tuned interaction is key to maintaining women's reproductive health.

The second paper is an opinion paper/commentary on the gaps and challenges to translating vaginal microbiome research. I co-authored the paper with Rebecca Brotman at IGS. The commentary addresses the potential of management, manipulation, and restoration of a robust vaginal microbiota  to improve women’s health and disease prevention. It makes a case for the development of a systems level understanding of how the vaginal microbiota is associated with gynecologic and reproductive health in order to develop effective interventional strategies. Consideration of timing of intervention and aspect of immune tolerance to vaginal microbes are also discussed. 

Jacques Ravel receives 2015-2016 International Blaise Pascal Research Chair

Jacques Ravel, PhD, Professor of Microbiology and Immunology, as well as Associate Director for Genomics at the Institute for Genome Sciences (IGS), both at the University of Maryland School of Medicine, has been named a 2015-2017 Blaise Pascal International Research Chair, one of the most prestigious European science awards. He is spending this year working at the Institut Pasteur in Paris, and over the next two years will divide his time between Paris and Baltimore. 

While at the Institut Pasteur, Dr. Ravel is working with Philippe J. Sansonetti, MS, MD, Professor of Microbiology at the Institut Pasteur and the Collège de France in Paris, and a member of the U.S. National Academies of Science, and a microbiologist who is interested in intestinal pathogens. Working with Dr. Sansonetti, Dr. Ravel will address the following central question: “Can a pathogen, to be successful, become a commensal, by subverting the fine-tuned balance between the host and the microbiome?” The pair are examining how some harmful microbes find niches within hosts, and transform themselves into more “friendly” bacteria. In particular, they will try to better understand how Chlamydia, which is pathogenic in some parts of the body, can live in the gastrointestinal tract without triggering problems. The Chair Blaise Pascal is funded by the Ile-de-France region of France. Dr. Ravel will also be organizing a symposium to highlight his research work in France, and to feature global collaborators and leading scientists. The symposium will take place at the College de France, a renowned research and teaching institution established in 1530 by King François 1st.  

“Being able to work at the Institut Pasteur, and with Dr. Sansonetti is a fantastic opportunity. For over 100 years, the Institute has continuously been a leader in the battle against infectious diseases,” said Dr. Ravel. “Having immersed myself in genomics over the past 15 years, the Chair Blaise Pascal is giving me a rare opportunity to re-engage myself with my original research focus in microbiology and interact with global leaders in microbiology, cell biology and immunology who are focusing on the role of the human microbiome in infectious diseases.”  

The Blaise Pascal Chairs were established in 1996 to honor foreign scientists in all disciplines. The award is named for the eminent 17th-century French genius, Blaise Pascal, who was a mathematician, philosopher, inventor and physicist. Previous laureates include Gerard Debreu (1983 Nobel Prize in Economics), Ahmed Zewail (1999 Nobel Prize in Chemistry), Georges Smoot (2006 Nobel Prize in Physics), Elizabeth Blackburn (2009 Nobel Prize in Physiology or Medicine), and Michael Levitt (2013 Nobel Prize in Chemistry).  

Dr. Ravel is one of two Blaise Pascal Chairs selected this year. The other is Piero Madau, PhD, a professor of astronomy at the University of California, Santa Cruz. 

For more information see the Institut Pasteur and University of Maryland School of Medicine websites.

Vaginal Microbiota and Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus

A collaborator, Dr. Sam Lai, has been studying cervicovaginal mucus (CVM) properties for quite some time. He did his Postdoctoral fellowship with Dr. Richard Cone at Johns Hopkins University, who is well-known is the field having written some of the main reviews on the topic. We worked with him to established a correlation between the composition of the vaginal microbiota and entrapment of HIV-1 particles by CVM. The work was recently published in the journal mBio and shows that communities dominated by Lactobacillus crispatus (CST I) are better changing the properties of CVM to trap HIV-1 particles than other communities. CVM associated with vaginal communities dominated by Lactobacillus iners do not have these properties. These two Lactobacillus spp. are quite different genomically, but also produce very different ratio of D/L lactic acid, with L. crispatus producing both isomers, but more D(-), while L. iners producing almost exclusively the L(+) isomers. This ratio could contribute to CVM protective properties. However, other factors are certainly playing a role. 

Here is the abstract of the paper, which you can find here: Nunn KL, Wang Y-Y, Harit D, Humphrys MS, Ma B, Cone R, Ravel J, Lai SK. 2015 Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with Lactobacillus crispatus-Dominant Microbiota. mBio 6:e01084-15.

Cervicovaginal mucus (CVM) can provide a barrier that precludes HIV and other sexually transmitted virions from reaching target cells in the vaginal epithelium, thereby preventing or reducing infections. However, the barrier properties of CVM differ from woman to woman, and the causes of these variations are not yet well understood. Using high-resolution particle tracking of fluorescent HIV-1 pseudoviruses, we found that neither pH nor Nugent scores nor total lactic acid levels correlated significantly with virus trapping in unmodified CVM from diverse donors. Surprisingly, HIV-1 was generally trapped in CVM with relatively high concentrations of D-lactic acid and a Lactobacillus crispatus-dominant microbiota. In contrast, a substantial fraction of HIV-1 virions diffused rapidly through CVM with low concentrations of D-lactic acid that had a Lactobacillus iners-dominant microbiota or significant amounts of Gardnerella vaginalis, a bacterium associated with bacterial vaginosis. Our results demonstrate that the vaginal microbiota, including specific species of Lactobacillus, can alter the diffusional barrier properties of CVM against HIV and likely other sexually transmitted viruses and that these microbiota-associated changes may account in part for the elevated risks of HIV acquisition linked to bacterial vaginosis or intermediate vaginal microbiota.