The Answer to HIV Transmission Might Lie in the Vaginal Microbiome
Author:
Douglas S. Kwon, MD, PhD
Our research has provided evidence that specific types of bacterial communities within the vagina—or the vaginal microbiome—can significantly impact a woman’s risk for acquiring HIV. Our work was focused on women in sub-Saharan Africa, where there is a cohort of HIV-uninfected young women living in an area with a very high incidence and prevalence of HIV.1 So we investigated the mechanism by which the vaginal microbiome impacts a woman’s risk of acquiring HIV.
What We Know From the Research
Women in sub-Saharan Africa seem to have very different baseline vaginal microbial communities than have been described in studies of primarily white women in high-resource settings. If you read many of the studies that have been done in the past—looking again at white women in countries in North America or northern Europe—the majority of healthy women will have a vaginal microbiome that consist primarily of a single type of bacteria called Lactobacillus. And that has been what is associated with health. Whereas, if you look at young women who are clinically healthy in a place like South Africa, most of those women have a baseline community that is actually quite different, dominated by many different anaerobes and has very little Lactobacillus. One of the takeaways that emerged in our research was that the baseline vaginal microbiome actually varies significantly depending on geography; and what we consider normal and healthy is not necessarily true across all regions of the world.
These different types of vaginal microbial communities can actually play an important role in affecting the amount of baseline immune activation within the genital tract. We and others have shown that women with certain types of bacterial communities that have these diverse, highly anaerobic structures actually have higher levels of baseline genital inflammation. That baseline genital inflammation can affect the immune environment within the genital tract and important reproductive health outcomes, such as HIV acquisition. We specifically showed that women with certain types of bacterial communities actually have higher levels of activated CD4 T cells within the genital tract as part of this elevated genital inflammation. And because those activated CD4 T cells are likely the first target of HIV infection, having more of those cells is a biological mechanism by which these bacterial communities can result in increased HIV risk.
What We’re Still Studying
One of the most common questions I hear is, “Why do these women in sub-Saharan Africa have baseline microbiomes that look so different than women in North America?” The simple answer is that we just do not know yet. There seem to be a lot of factors—some of them might be related to the host. Some of them might be related to the environment, possibly diet or vaginal hygiene practices. No one really knows why that is.
Another question that has come up is, “If we think that these certain vaginal microbiomes might actually have a negative impact on reproductive outcomes such as HIV, and things like pre-term birth and fertility, how can we actually alter these microbiomes to promote more favorable reproductive outcomes?” And that also is an area where we, unfortunately, do not know enough yet. Certainly we, and others in the field, have been trying to understand whether those communities can be manipulated by either giving things like a probiotic, for example delivering healthy Lactobacillus to the vagina to try to promote colonization with more Lactobacillus.
I think that there are a lot of caveats with those approaches, and so how to create durable changes that are more favorable for positive reproductive outcomes still is a challenge in the field, but it is something people are driving more toward now that we better understand these relationships between vaginal bacteria and reproductive health.
Another big question we are really interested in is understanding is, “What are the specific mechanisms by which certain bacterial communities induce this genital inflammation and increased HIV acquisition risk?” Can we identify the particular molecular mechanisms by which these bacterial communities are being sensed by the host’s innate or adaptive immune system within the genital tract that then translate into this increased acquisition risk?
If we can better understand those specific mechanisms, then we can potentially intervene to block that genital inflammation to reduce risk or reduce poor reproductive outcomes, even if we cannot durably alter the bacterial communities themselves. I think that’s one of the primary gaps we and others have been focused on in addition to better understanding how we can manipulate these communities to promote health.
Douglas S Kwon, MD, PhD, is a physician scientist at the Ragon Institute of MGH, MIT, and Harvard and is Director of Clinical Operations at the Ragon Institute.
Reference:
- Gosmann C, Anahtar MN, Handley SA, et al. Lactobacillus-deficient cervicovaginal bacterial communities are associated with increased HIV acquisition in young south African women. Immunity. 2017;46(1):29-37. doi:10.1016/j.immuni.2016.12.013.