7 February 2024
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Healthcare systems around the world have historically been designed by men, with “white males” traditionally being considered the clinical “norm” for study populations. Unsurprisingly, leaving females out of the conversation has resulted in persistent healthcare inequalities. From being excluded from clinical trials, to longer waiting times to see doctors, to not being taken seriously by healthcare professionals; the healthcare system has continually shown its bias. 

Over the past few decades more and more research has revealed differences in disease presentation between sexes. Neurodegenerative diseases, mental health conditions, autoimmune diseases, and even infectious diseases like COVID-19 have all been shown to affect males and females differently. Some of this difference can be attributed to the variation between the X and Y chromosomes, but for many conditions the differences remain a mystery. 

One healthcare area where sex differences are only recently being explored is the microbiome. The human microbiome refers to the vast microbial community that exists within each of us. It is made up of 10-100 trillion symbiotic microbes that reside on and in our bodies. Studies have shown that an imbalance in the microbiome is an underlying cause of many diseases, and recently our understanding of how biological sex impacts the microbiome is evolving. 

Studies into sex differences in the microbiome can be tricky due to other factors which play a huge role such as diet, age and genetics. However some differences between male and female gut microbiomes are emerging, for example some studies suggest that the diversity and richness of bacterial species within the gut microbiota appears to be greater in females.

Recently, attention is turning to the microbiome of the female reproductive system. Traditionally, the uterus was thought to be a sterile environment, but recently researchers have found that differences in uterus microbiome composition can affect ability to conceive and maintain pregnancy.

The vaginal microbiome is a complex and dynamic system that is constantly fluctuating throughout the menstrual cycle, and over a lifetime. Imbalance in the vaginal microbiome is associated with increased risk of acquiring sexually transmitted diseases, including gonorrhoea, HIV and chlamydia; is linked with endometriosis and infertility; and even is associated with a higher risk of developing cervical cancer.

Generally, a healthy vaginal microbiome is dominated by lactic acid-producing bacteria, commonly Lactobacillus species (although some research suggests there may be variation due to ethnicity). In this symbiotic relationship, Lactobacillus protect their host against pathogenic invasion, and their host provides Lactobacillus with a source of nutrients. A reduction in Lactobacillus species, and an increase in facultative and obligate anaerobes such as Gardnerella, Pretovella or Atopobium, is associated with conditions such as dysbiosis and bacterial vaginosis (BV). 

While there’s still a long way to go before we fully understand how sex and the microbiome impact health, several pioneering companies are taking strides to achieve this goal.

Freya Biosciences

Freya Biosciences are a Denmark based biotech company, specialising in women’s health. 

Freya focuses on microbial immunotherapies, investigating the impact of the vaginal microbiome on reproductive health.

In 2023 a Freya-funded proof-of-concept study demonstrated the use of antibiotic-free vaginal microbiota transplantation (VMT) on a patient with vaginal dysbiosis and a history of complicated pregnancies. Cervicovaginal secretions from a healthy donor (Lactobacillus-dominant vaginal microbiome) were transferred to the patient. After just one treatment, there was a complete shift in her microbiome to be Lactobacillus dominant. This microbiome shift has remained stable for 1.5 years, and the patient has since successfully delivered a healthy baby at full term. 

Freya found more success with another proof-of-concept trial, which demonstrated a rapid change in patients from a dysbiotic vaginal microbiome to a Lactobacillus-dominated vaginal microbiome following administration of Freya’s lead drug candidate, FB101 (also VMT) for just three days. 

While still in its infancy, VMT appears have strong potential for treating severe vaginal dysbiosis and may offer hope to many women struggling with infertility. Freya Biosciences – who have more clinical trials in the pipeline, and who recently secured an impressive $38 million in Series A financing – look set to unlock that potential. 

Evvy Biosciences

Evvy Biosciences are developing technology that could complement the therapeutics being developed by companies such as Freya. Evvy is leveraging the opportunities provided by AI and precision medicine to discover biomarkers for female health. Evvy was founded because “the female body shouldn’t be a medical mystery” yet many datasets available for training AI lacked samples from female participants.

Last year, Evvy got $14 million funding to expand access to its testing and care platform.  While providing a personalised diagnostic service using at-home vaginal microbiome testing, they are also gathering data and using AI to discover novel molecular signatures for female health diagnostics.  They hope this will feed into improved outcomes in fertility and pregnancy.

Juno Bio

Juno Bio are also on a mission to empower people to understand their own vaginal microbiome.  

With many cases of vaginal dysbiosis and BV being asymptomatic, many people may not realise anything is wrong with their vaginal microbiome until complications arise. For those that suspect something is wrong, there have historically been limited options for getting a deeper understanding.

In order to address this, Juno Bio have generated microbiome repositories based on over 1000 vaginal samples. Using this data, they have developed a do-it-yourself kit to enable anyone to get a personalised microbiome profile. 

At-home kits such as these have potential to empower people who may otherwise have felt fear or embarrassment in going to healthcare professionals to gain a deeper understanding of their vaginal health.

Osel Inc.

Also looking to treat and prevent conditions associated with an abnormal microbiome are Osel Inc., a California based company developing a portfolio of Live Biotherapeutic Products, with a focus on women’s health.

BV is often treated using antibiotics (such as metronidazole) in the hope that BV-related microbes will be killed, leaving space for healthy vaginal microbiota to grow. However, antibiotic treatment generally leads to a high recurrence rate.

Osel are developing “Lactin V”, a vaginally-administered drug containing a single strain of Lactobacillus crispatus, for the treatment of recurrent BV, preterm birth and recurrent urinary tract infections. A phase 2b trial showed that using Lactin-V after treatment with metronidazole for bacterial vaginosis resulted in significantly lower incidence of recurrence of BV. 

Recently, Osel also completed a study showing the safety and tolerability of Lactin-V in pregnant people at high-risk of preterm birth. The link between BV and preterm delivery is well-established, but pregnant people are a difficult group to target for new treatments. They are often excluded from clinical trials, and new treatments can be viewed with fear. However, the majority of participants in this study were happy to use Lactin-V again. On the back of these positive safety results, follow up studies will explore how Lactin-V can be used to treat BV in this high-risk group.

These exciting developments merely scratch the surface of opportunities for harnessing the human microbiome. We are looking forward to seeing the potential of microbiome-based treatments and how they offer new hope for people struggling with reproductive health.


 

We have used the terms “woman”/”women”/”female” in this article. We use the term “female” in the context of discussing biological characteristics, but we strive to do so with the sensitivity and understanding that gender identity is a separate and complex aspect of human experience, encompassing a spectrum beyond the binary categories of “man” and “woman”. We recognise that not everyone who can benefit from this technology are women (for example, transmasculine people), and that conversely there are women who cannot benefit from this technology.

 


About the Authors

This blog was co-authored by Sarah Harvey and Amelia Jones.

Sarah is an associate patent attorney working as part of our life sciences team. She has a degree in Biological Sciences from Oxford University. She completed her PhD at Warwick University in plant pathology looking at how pathogen effectors manipulate the plant immune response. Sarah then worked as a post-doc in the Centre for Novel Agricultural Products at York University on plant responses to biotic stress.
Amelia is a trainee patent attorney in our life sciences team. Amelia has an undergraduate BSc degree in Biochemistry from Cardiff University with an Industrial placement at GlaxoSmithKline and a PhD Cancer Sciences from University of Manchester.
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