Summary

Our project aims to develop an affordable, at-home device that uses an E. coli biosensor to detect the quantity of putrescine, a known biomarker associated with Bacterial Vaginosis. Consequently, this will allow women to continuously self monitor their vaginal microbiome.

Status Quo

Bacterial Vaginosis (BV) is a vaginal condition that currently affects about one in three women globally. (1) In the status quo, BV is classified as a syndrome, meaning it is based on the presence of symptoms rather than having a clear biomolecular basis. While the exact cause of BV is not yet known, through human practice conversations and research of the literature, it is believed that an imbalance of Lactobacillus spp. and Gardnerella Vaginalis causes BV. Gardnerella is by no means a bad bacteria, it exists naturally in everyone’s vaginal microbiome in low levels. BV is suggested to be a disease where there is more gardnerella than lactobacillus. (2)

BV’s symptoms include vaginal dryness, itching or burning, fishy odor, and is linked to increased risk factors for preterm birth and infertility. (3) As of now, it is treated using prescriptive antibiotics like metronidazole and clindamycin. However, instead of solely targeting bacteria thought to cause BV, antibiotics can cause a ‘scorched earth’ outcome for the vaginal microbiome and ubiquitously kill off the healthy and protective bacteria as well. This leads to more than 80% of women experiencing a recurrence of a BV infection within 6 months. (4) As of now, there is still no effective cure for BV and an incomplete understanding of its cause. Considering that this disease affects about 30% of women of reproductive age, the state of research on this topic is insufficient. Currently, the procedure to diagnose BV is to follow Amsel's criteria or the Nugent score. The Nugent score is a number awarded based on a gram stain of a swab taken from the microbiome. Most clinicians prefer Amsel’s criteria which is defined as a list of clinical findings that can diagnose the presence of BV. (5)

Problem

Like any other human microbiome, the vaginal microbiome is both unique and dynamic. Demographically, Asian and white women are dominated by 80-90% Lactobacillus, whereas in Black and Hispanic women, Lactobacillus makes up about 60% of the vaginal microbiome. (7) Evidently, everyone’s baseline looks slightly different, and so a single snapshot diagnostic tool will miss situating the data within appropriate and personalized context. Additionally, the microbiome is also incredibly dynamic. Factors like age, pregnancy, menstrual cycle, diet, sleep, health, presence of Human Papillomavirus (HPV), proximity to menopause, sexual intercourse and more will all change the flora of the vaginal microbiome.

As just one individual progresses through their life, they will experience a wide range of microbial states. For example, the vaginal microbiome of a 40 year old woman entering perimenopause is very different from that of a 23 year old who is ovulating. Therefore, it is difficult to personalize tracking of the vaginal microbiome and make generalizations through just observing trends in research. There are one time use swabs that observe vaginal pH, but no device that tracks the changes over time. As such, little to no products are commercially available that monitor vaginal health on a day to day basis.

Our Solution

While there is still no widespread and affordable over-the-counter (OTC) for Bacterial Vaginosis, we believe that our diagnostic foundation in tracking the microbiome’s changes over time can still allow users to understand and self-monitor their health. Furthermore, our longitudinal data is especially useful for recurrent BV patients. For example, it could help a user see if their BV is getting better on its own so they might not need to take antibiotics. It could also be critical information to inform fertility planning for women who are attempting to conceive. Our device is NOT a replacement for medical expertise, we see it as a way of empowering women to understand their health and their bodies. We hope that it can help them self identify triggers that cause flare ups or recessions in their BV. It is no replacement for conversations with medical providers. Our device stands to be the first of its kind to introduce a continuous monitoring system at home. The impact of our device would be immediate, allowing women to have fast access to their health data and able to make rapid changes accordingly. We chose to use whole cell biosensing because of the limitations of the lab we operated in. We replicated a putrescine repressing circuit from Selim et al. (8) and used multiple experimental methods to validate it. This included growth curves, and an array of dose responses. More details are listed in the parts page here.