Just as Smita Gopinath, Ph.D., was setting up her microbiology and immunology lab at Harvard T.H. Chan School of Public Health, the COVID-19 pandemic struck and shut things down. With no lab space or animal facility to house mice she could work with, Gopinath adapted to do whatever research she could.
She grew strains of lactobacillus bacteria from the vaginal microbiome, provided by the Human Microbiome Project, and tested whether they had any effect on human immune cells.
“There's been lots of really good studies looking at lactobacilli’s association with epithelial cells,” Gopinath told Fierce Biotech in an interview. “I had not really found a lot of papers out there looking at what these bacteria might do to immune cells.”
What they do, it turns out, is produce a family of chemicals that have anti-inflammatory properties. The results of a study of vaginal inflammation in mice, published in Cell Host & Microbe on Oct. 17, could lead to new treatments for bacterial vaginosis (BV), a common and painful affliction that also increases risk for sexually transmitted infections.
The chemicals are called beta-carboline alkaloids, and six of the nine family members identified by the researchers showed anti-inflammatory capabilities. Once Gopinath finally had her mice, she and her team applied the standout beta-carboline, perlolyrine, to inflamed vaginas of a genital herpes mouse model.
Treating the mice once a day with perlolyrine for four days, starting four days after herpes infection, significantly reduced disease scores and improved their survival.
A further analysis of female genital tract fluid from both healthy individuals and those with BV revealed that beta-carbolines were more common in healthy people, strengthening their link to the positive health effects of lactobacillus in the vaginal microbiome.
“BV is a huge market,” Gopinath said. The disease can have a prevalence as high as 60% in certain populations, and its global prevalence ranges from 23% to 29% of reproductive-age women. “We're still stuck at treating this with antibiotics that were standard of care in the '70s. There’s a lot more we could be doing.”
The vaginal microbiome hasn’t received as much attention as the one in the gut, but it is known to influence health. There are two main forms the vaginal microbiome can take: The microbial community can be dominated by bacteria called lactobacilli or have few lactobacilli and instead be dominated by a high diversity of other bacteria. Lactobacillus dominance is associated with better fertility outcomes, like giving birth at term, whereas a lack of lactobacilli can lead to BV.
BV is a well-known risk multiplier for other health problems.
“If you have a BV flare, you're more likely to acquire sexually transmitted infections, you're more likely to transmit them, you are at a high risk of poor obstetric outcomes,” Gopinath said. “We really don't understand mechanistically how any of this works.”
Gopinath’s goal was to focus on what lactobacilli might be doing to promote health. Screening supernatant fluids from different lactobacillus strains, she saw that some lactobacillus crispatus were able to suppress the activity of pro-inflammatory interferons in activated immune cells.
Supernatant is essentially a cell slurry made up of various compounds and chemicals. To identify which compounds in this slurry were anti-inflammatory, Gopinath turned to a visiting chemist from Sungkyunkwan University in South Korea named Ki Hyun Kim, Ph.D.
“My wife is an OB-GYN medical doctor,” Kim told Fierce in a joint interview with Gopinath. “According to her interest, I’m also interested in some vaginal bacteria.”
Kim is a natural products chemist, skilled in isolating compounds from samples. Once he identified a compound, Gopinath tested its ability to suppress inflammation.
“[Kim] was isolating compounds faster than we could test,” Gopinath said.
Gopinath is now exploring the effects of beta-carbolines in animal models of preterm birth and is also open to industry partnerships to move perlolyrine forward. For her work so far, she’s already teamed up with a contract research organization, BioDuro-Sundia, which synthesized the beta-carbolines used in the study.