Changes in Microbiome Predict Risk for Sexually Transmitted Infections

Highlights

• Specific changes in the cervicovaginal microbiome set the stage for chlamydia
• Women of color disproportionately affected by infections but understudied
• Team reveals previously unknown subtype of BV, bacterial vaginosis

BRONX, N.Y. and BUFFALO, N.Y. - Women who develop bacterial vaginosis (BV) often later acquire chlamydia, a common and potentially serious sexually transmitted bacterial infection. Now, researchers at Albert Einstein College of Medicine, Roswell Park Comprehensive Cancer Center and the Icahn School of Medicine at Mount Sinai have found that BV actually consists of two subtypes - one of which significantly increases the risk of developing chlamydia infections. The findings were made in a population of young Black and Hispanic women, who are disproportionately affected by both BV and chlamydia, but are historically understudied. The study, one of the largest and most comprehensive of its kind, was published online today in the journal Cell.

"It was already known that BV raises a woman's risk for acquiring chlamydia, but it wasn't clear how the microbiome imbalances seen in BV contribute to that risk," says study co-leader Robert Burk, MD, Professor of pediatrics, microbiology & immunology, obstetrics & gynecology and women's health, and epidemiology & population health at Einstein and vice chair for translational research in the department of pediatrics at Montefiore Einstein. "This research shows that specific changes in the cervicovaginal microbiome set the stage for chlamydia. And it shows that targeting treatment against the more-dangerous BV subtype could potentially prevent many women from developing chlamydia, which is particularly prevalent in historically underserved communities."

BV affects at least 30% of women at any given time and up to 50% of Black and Hispanic women. Black and Hispanic adolescent and young adult females have a five-fold higher risk of acquiring chlamydia compared with their white counterparts.

"This study was made possible by the participation of young women of color, who are at highest risk for this infection and most likely to experience its negative impact," says study co-author Angela Diaz, MD, PhD, MPH, dean of Global Health, Social Justice and Human Rights at the Icahn School of Medicine at Mount Sinai. "We hope that our research and future studies continue to address disparities in healthcare, improve access to treatment and enhance our approach to personalized care."

Two types of BV infection discovered

BV is caused by imbalances in the cervicovaginal microbiome-the collection of bacteria naturally found in the genital tract. Common symptoms include vaginal discharge, itching or irritation, and burning sensation during urination, although many cases are asymptomatic. BV can be readily treated with antibiotics.

In the new study, the researchers used advanced DNA-sequencing technology to analyze the cervicovaginal microbiomes of 560 adolescent and young adult Black and Hispanic females. The analyses were performed before infection with chlamydia, at the time of infection, and following antibiotic treatment, allowing the researchers to identify which combination of cervicovaginal bacteria is associated with subsequent chlamydia infections.

The analysis detected two distinct subtypes of BV. One subtype - a collection of ten different interconnected bacterial types that account for about 40% of all BV cases - contributed to increased risk for acquiring chlamydia, subsequent reinfection with chlamydia, and complications such as pelvic inflammatory disease.

Roswell Park epidemiologist and cancer prevention expert Nicolas Schlecht, PhD, MSc, who helped lead research that revealed significant discoveries about changes in the cervicovaginal microbiome and their connection to development of potentially serious infections.

"This study adds to the growing evidence of the impact of BV on the risk of clinically significant infections, including chlamydia and human papillomaviruses, that can cause cervical cancer," says Nicolas Schlecht, PhD, MSc, Professor of Oncology in the Department of Cancer Prevention and Control at Roswell Park Comprehensive Cancer Center, noting in particular work published by this group of collaborators in Nature Communications in 2022. "It's our hope that this work to reveal the connections between the cervicovaginal microbiome, common infections like chlamydia and HPV, and cancer might help advance the larger effort to prevent more cancers and other resulting conditions." Dr. Schlecht, who was co-lead and co-author of the study, also serves as an adjunct faculty member at Einstein.

Treating one infection to prevent another

"These results are particularly significant for communities of color and could lead to a wholly new approach for clinically managing BV and chlamydia," says Dr. Burk, who is also a clinical geneticist at the Children's Hospital at Montefiore and a member of the National Cancer Institute-designated Montefiore Einstein Comprehensive Cancer Center. "We can now determine which BV cases are most worrisome and should be closely monitored. Detecting and treating these infections could substantially reduce the incidence of chlamydia and its serious consequences including pelvic inflammatory disease, infertility, and miscarriage. The findings also suggest that altering the cervicovaginal microbiome could be a strategy for both treating BV and preventing chlamydia."

Dr. Burk likens BV to high blood pressure. "High blood pressure is silent, but it's not harmless," he says. "We routinely screen for high blood pressure because it's a major risk factor for cardiovascular disease. By the same token, BV is more or less silent but is a major risk factor for chlamydia. Regularly screening for and treating BV would go a long way toward preventing chlamydia."

At present, advanced cervicovaginal microbiome analysis is not available to most clinicians. But, says Dr. Burk, "I can envision a scenario where it would be readily accessible to most doctors and perhaps even incorporated into home tests, like we have now for COVID-19."

"This study represents a breakthrough by showing that the risk posed by a relatively benign bacterial condition such as BV can be assessed through microbiome analysis," says Mykhaylo Usyk, PhD, research assistant professor of pediatrics and of microbiology & immunology and first author of the paper. "Our findings suggest that only a subset of BV cases may require treatment to prevent subsequent infections with chlamydia."

This work was supported in part by an R01 grant from the National Institute of Allergy and Infectious Diseases (AI072204) as well as National Cancer Institute Cancer Center Support Grants to the Einstein Cancer Research Center (CA013330) and Roswell Park Comprehensive Cancer Center (CA016056). Additional funding was provided by the Icahn School of Medicine at Mount Sinai.

About Roswell Park Comprehensive Cancer Center

From the world's first chemotherapy research to the PSA prostate cancer biomarker, Roswell Park Comprehensive Cancer Center generates innovations that shape how cancer is detected, treated and prevented worldwide. Driven to eliminate cancer's grip on humanity, the Roswell Park team of 4,000 makes compassionate, patient-centered cancer care and services accessible across New York State and beyond. Founded in 1898, Roswell Park was among the first three cancer centers nationwide to become a National Cancer Institute-designated comprehensive cancer center and is the only one to hold this designation in Upstate New York. To learn more about Roswell Park Comprehensive Cancer Center and the Roswell Park Care Network, visit www.roswellpark.org, call 1-800-ROSWELL (1-800-767-9355) or email [email protected].