Improving Microbial Balance in Female Genital Tract May Boost Health Outcomes

Advances in gene sequencing and computational biology have revolutionized the study of the microbiome over the past decade. But compared with other bodily systems like the gastrointestinal tract and skin, much less attention has been paid to the microbiome of the female genital tract. This is despite its important role in modulating reproductive health.

Raina Fichorova, MD, PhD, is the director of the Laboratory of Genital Tract Biology, the Walter Channing Distinguished Chair in Obstetrics and Gynecology, the inaugural BWH OBGYN vice chair for Research at Brigham and Women’s Hospital, and professor of Obstetrics, Gynecology and Reproductive Biology at Harvard Medical School. She is also a leader in studying host-microbe interactions in the female reproductive tract, including their role in inflammation, resilience to infection and reproduction. Some of her efforts have focused on the development of a novel biotherapeutic treatment, which she has patented and is now working to bring into clinical trials.

“There is an overwhelming body of evidence showing that the resident vaginal microbes are a fundamental part of the fabric of innate immunity in the female genital tract,” Dr. Fichorova says. “They have consequences not only for women’s health, but also for the health and development of their offspring.”

Addressing an Unmet Need in Women’s Health

Central to the work in Dr. Fichorova’s laboratory is the characterization of the microbes that play a role in bacterial vaginal dysbiosis, which is associated with increased inflammation in the genital mucosa, increased susceptibility to sexual transmitted infections and adverse pregnancy outcomes.

Despite available antibiotic treatment, an estimated 21.2 million women of reproductive age in the United States have this condition, including 23% of white women, 51% of Black women and 32% of Latina women. In African countries, where Dr. Fichorova has conducted much of her research, the prevalence among reproductive age women is between 35% and 50%.

“There is an unmet need for better ways to treat this condition, which affects up to half of women of reproductive age in the most vulnerable populations around the globe,” she says. “There are major gaps in the study of this condition and how to address it therapeutically.”

Dr. Fichorova and her team have developed metrics to distinguish good from bad maternal bacteria and to identify microbes that can affect the offspring either directly or through epigenetic changes, due to the presence or absence of inflammation in the uterus and placenta. The investigators discovered that maternal bacteria ascending to the placenta are associated with newborn inflammation and that maternal bacteria are also linked to epigenetic regulation of inflammatory genes in the placental tissue.

“We’ve found that certain types of lactobacilli in the uterus and placenta reduce inflammation at all molecular checkpoints,” Dr. Fichorova says.

Developing a Live Biotherapeutic Treatment

One effort to come from this work is the development of live biotherapeutics, which “have the potential to reduce inflammation and prevent the ascendance of harmful bacteria to the placenta,” according to Dr. Fichorova.

In 2021, Dr. Fichorova and her colleagues at the Brigham were granted a patent for a mixture of strains of lactobacilli that has the potential to correct the microbial balance in the female reproductive tract.

“We have identified and cloned bacterial strains of the human vaginal microbiome obtained from healthy moms who delivered healthy babies at term here at the Brigham,” she says. “These strains synergistically colonize the human vaginal cells, are homeostatic and noninflammatory and have genomes that are fully characterized.”

In addition to the biotherapeutic blend, the patent includes an algorithm to synthesize a unique cocktail of these strains in optimal proportions.

With funding from the National Institutes of Health as well as internal funding from within the Brigham through its “Shark Tank” program, Dr. Fichorova and her colleagues have made progress toward developing vaginal delivery systems for their biotherapeutic. They are also collaborating with the pharmaceutical industry.

“The successful translation of our research concept and implementation of a live biotherapeutic device would contribute to improved reproductive and sexual health and also reduce preterm birth, infant mortality and disability rates associated with a disturbed vaginal microbiome,” she says. “Our research has the potential to benefit at least 500 babies born preterm at the Brigham each year.”

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