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. 

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.

The vocabulary of microbiome research: a proposal

Julian Marchesi and myself have written an editorial that attempt at stimulating discussions on harmonizing the use and definition of terms in microbiome research. We believe it is important as so many misnomers are found in the literature. We hope that this editorial will stimulate discussions and further refinements of these terms. You can comment on NCBI or on the Microbiome website The editorial was published in Microbiome, which I am the Editor in Chief. 

Here is the abstract:

The advancement of DNA/RNA, proteins, and metabolite analytical platforms, combined with increased computing technologies, has transformed the field of microbial community analysis. This transformation is evident by the exponential increase in the number of publications describing the composition and structure, and sometimes function, of the microbial communities inhabiting the human body. This rapid evolution of the field has been accompanied by confusion in the vocabulary used to describe different aspects of these communities and their environments. The misuse of terms such as microbiome, microbiota, metabolomic, and metagenome and metagenomics among others has contributed to misunderstanding of many study results by the scientific community and the general public alike. A few review articles have previously defined those terms, but mainly as sidebars, and no clear definitions or use cases have been published. In this editorial, we aim to propose clear definitions of each of these terms, which we would implore scientists in the field to adopt and perfect.

Full citation: Marchesi JR, Ravel J. The vocabulary of microbiome research: a proposal. Microbiome. 2015 Jul 30;3:31. doi: 10.1186/s40168-015-0094-5. eCollection 2015. PubMed PMID: 26229597; PubMed Central PMCID: PMC4520061.