Modifying the vaginal microbiome to promote health

March 8, 2022

Researchers have discovered a simple way to grow L. iners in culture. This led to discovery of a potential treatment to selectively block the growth of L. iners, promoting the growth of Lactobacillus crispatus, a bacterial species associated with optimal genital health, according to a news release Massachusetts General Hospital.

In addition to Mass General, other collaborators are from Massachusetts Institute of Technology and Harvard University.

“L. iners is the most abundant and common vaginal bacterial species worldwide, but it is poorly studied because scientists have had difficulty growing it in lab under conditions used to culture species like L. crispatus,” explains Seth Bloom, MD, PhD, Instructor in the Infectious Diseases Division at Massachusetts General Hospital and Harvard Medical School who was lead author on the study. Bloom and colleagues found that adding the amino acid cysteine to standard Lactobacillus culture media allowed them to grow L. iners strains from samples collected from U.S. and South African women.

The female genital tract is naturally colonized by mixed communities of bacteria, known as the vaginal microbiome. When these communities are dominated by species such as Lactobacillus crispatus, they provide important protective functions in genital health. But overgrowth of certain other bacterial species is linked to a condition known as bacterial vaginosis (BV). BV affects nearly 30% of women around the world, carrying increased risk for sexually transmitted diseases, HIV, and – in pregnant individuals – premature birth. Unfortunately, current antibiotic-based treatments for BV are poorly effective with high rates of recurrence.

Surprisingly, when the researchers analyzed a novel collection of more than 1,200 vaginal Lactobacillus genomes from more than 300 women across four continents, they found that none of the species were able to make their own cysteine. This finding was confirmed in experiments conducted with Ben Woolston, PhD, and Emily Balskus, PhD, at the Harvard Department of Chemistry and Chemical Biology.

The team therefore hypothesized that all vaginal Lactobacillus species require external cysteine sources. They measured cysteine concentrations in vaginal fluid samples from South African women with high rates of BV, finding that higher vaginal cysteine levels were linked to Lactobacillus-dominant microbiomes while BV was associated with low cysteine levels. 

“The results suggested all vaginal lactobacilli acquire cysteine from their environment, but L. iners’s ability to do so was more limited than other species,” says Bloom. “Indeed, when we looked at the genomes, we saw that all species except L. iners had multiple systems that are predicted to transport cysteine or its oxidized form, cystine.” The team therefore tested effects of compounds known to inhibit cystine uptake, finding that cystine uptake inhibitors selectively blocked growth of L. iners in the lab, but not other Lactobacillus species.

The team emphasizes that several important questions remain. It isn’t yet clear how L. iners takes up cysteine from its environment, and more potent versions of the inhibitors may need to be developed before the strategy can be used to treat patients. Even so, the study is a promising step forward for this common but difficult-to-treat condition.

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