In previous articles we covered the 5 types of vaginal environments, it’s connection to cervical health, and how good bacteria help to keep your body safe. Today we will discuss what happens when the ‘bad’ bacteria begin to take over and how these anaerobic bacteria may actually assist viral pathogenesis.
For a quick review, here are the 5 types, with Types 1, 2, and 5 being the healthiest and dominated by bacteriocin-producing Lactobacillus species, and Type 4 being the least healthy and dominated by the anaerobic bacteria.
Remember from Part III that the bacteriocins produced by the lactobacilli help protect the body from colonization by foreign bacteria by interrupting their ability to reproduce or stick together. Also, these good lactobacilli of Types 1, 2, and 5 help maintain a low pH (via D-Lactic Acid hydrogen peroxide) production which helps to inhibit the growth of bacterial STI’s such as chlamydia, gonorrhea, and Gardnarella vaginalis.
While you may predominately have one Type over another, remember these bacterial levels can fluctuate. Healthy levels of lactobacilli are heavily influenced by the amount of estrogen/progesterone in your body over the course of the month, being depleted as you approach your period; actions such as smoking, douching, and having sex recently can decrease your levels of healthy bacteria and make your body more susceptible to growth of anaerobic bacteria.
So what happens in your body if the anaerobic bacteria become dominant, causing a transition to a Type 4 environment, and how does it make your body more susceptible to viral infection?
In the vagina there is a mucosal layer that helps protect from infection by creating a barrier – during dysbiosis (the term for a bacterial imbalance) integrity of this barrier is disrupted, which may help the virus to enter the body. Dysbiosis puts the body at risk in a several ways, specifically protein dysfunction and mucus breakdown.
Below is a highly simplified cross-section of the layers of epithelial cells just to give an idea generally where the major cell types are located; the mucosa is the outermost layer and the basal cells are the deepest subset of cells of the epithelium.
A study of Rwandan sex workers found an association between dysbiosis and HIV infection. This occurred because the dysbiosis disrupted a very important cytoskeletal protein (responsible for tissue support and maintaining the cell’s shape) and consequently resulted in increased cell death and desquamination – scientific jargon for shedding the outer layer of tissue. It is possible that this process may also be advantageous for the human papillomavirus by allowing it to access the basal epithelial cells, those cells at the deepest layer of epithelial cells where the virus can replicate/persist and can cause cervical intraepithelial neoplasia (CIN).
Once a viral infection occurs, the next thing the virus wants to do is replicate itself and release all its offspring viruses, a process called ‘particle shedding’. Bacterial vaginosis has shown a higher rate of particle shedding of both the HIV virus and herpes simplex 2 (HSV-2), and specifically the G. vaginalis bacteria in in vitro studies is capable of inducing replication of the HIV virus. So it is logical to wonder if this dysbiosis caused by a deficiency in lactobacilli and overabundance of anaerobic bacteria creates an environment that makes infection and replication easier for the HPV virus, too, thereby increasing the likelihood of persistent infection and consequential CIN.
Another consequence of dysbiosis is decreased mucus production. In the body, mucus can function as a trap for foreign particles and pathogens – like flypaper for the body – keeping them stuck until the immune system can take care of them or until they are expelled from the body.
The good bacteria are able to produce proteins that help protect your body and likewise bad bacteria can produce enzymes that break down your body’s defenses. In cases of bacterial vaginosis there are high levels of Prevotella and species Bacteroids. These bacteria produce sialidases, enzymes that breakdown mucin, which is a major component of mucus.
Studies have shown vaginal environments with abnormal bacteria levels do indeed have less mucus and consequently have a decreased capability to trap viral particles. These low-mucus environments also have an increased amount of cervical epithelium exposed, increasing the risk for infection.
One study in particular found Type 1 vaginal environments (L. crispatus) with high amounts D-lactic acid had a high level of HIV-1 pseudovirus that was trapped, but Type 3 environments (L. iners) with low levels of D-lactic acid or those with BV-associated Gardnarella vaginalis had a lot of viral particles that were able to go free.2
As with many interactions amongst the microbiota, it is hard to tell the chicken from the egg – do these anaerobic bacteria act together with viruses to affect cellular homeostasis pathways, or does this occur independently, leaving a more hospitable environment for the viruses if it happens to come along at the right (wrong?) time?
While we may not know how every type of ‘bad’ bacteria can alter this environment to the benefit of the viral pathogens, it should be pointed out which are common in Type 4 environments and are associated with BV – Gardnarella vaginalis and species of Sneathia bacteria.
G. vaginalis is often found in the vaginal environments of prepubescent girls, which lack high amounts of estrogen/progesterone. In these low-hormone environments, anaerobic bacteria dominate. The bacteria are also found in women with Type 4 environments. The cervix of Type 4 women and prepubescent girls are both more susceptible to HPV infection; G. vaginalis may have a role in this process.
Sneathia bacteria are associated with miscarriages and premature labor, but they are also present in HPV+ women and women with infections that have progressed to CIN and cervical cancer. These bacteria belong to a genus of bacteria called Fusobacterium, which have been found to increase inflammation, alter immunomodulatory pathways, and interrupt crucial cell survival/proliferation pathways.
So the important lesson here is that taking care of our bodies is more than the standard eating healthy, exercising, staying hydrated regimen that we expect. We have lots of little organisms that are constantly interacting with each other, and if we don’t take care of them, they can’t take care of us.
Take a look at your risk factors and behavior. If you are concerned that you may have a bacterial imbalance (you may be able to tell by a presence of foul smell or discharge), be sure to talk to your doctor sooner rather than later because the little guys responsible for those signs may be putting you at an increased risk for viral infection.
Coming up in the final installment, Part 5: How probiotics and prebiotics may help clear BV and HPV infections.
These installments are synopses of a review that you can read in full here.
1Mitra, A., Macintyre, D. A., Marchesi, J. R., Lee, Y. S., Bennett, P. R., & Kyrgiou, M. (2016). The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: What do we know and where are we going next? Microbiome,4(1). doi:10.1186/s40168-016-0203-0
2Nunn, K. L., Wang, Y., Harit, D., Humphrys, M. S., Ma, B., Cone, R., . . . Lai, S. K. (2015). Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with Lactobacillus crispatus -Dominant Microbiota. MBio,6(5). doi:10.1128/mbio.01084-15