Researchers have now discovered a mechanism for differences in the protective effects of vaginal Lactobacillus bacterial species in preventing chlamydial infections.
Humans are metaorganisms or superorganisms, which means that each human is an ecosystem containing billions of microorganisms that live in and on us. These organisms are is called the microbiome or microbiota. Researchers are beginning to understand how these organisms contribute to overall health and disease, and how they affect our responses to medicine or therapeutic interventions. Some species of vaginal Lactobacillus bacterial species protect against chlamydial infection and some do not. Researchers have now discovered that the key to this protection is in the metabolism of the bacteria and their production of specific chemical forms, called isomers, of lactic acid. Like many organic molecules, lactic acid can be produced as an L isomer or a D isomer.
Research led by Jacques Ravel showed that only D-lactic acid was protective. The protective species of Lactobacillus (L. crispatus and L. jensenii) produced both L- and D-lactic acid, but they made much more D-lactic acid. The species (L. iners) that was associated with increased risk of chlamydial infection produced only L-lactic acid. Experiments with cultured vaginal or cervical epithelial cells showed that exposure to D-lactic acid changed gene expression resulting in reduced amounts of the growth factor receptor that Chlamydia trachomatis uses to gain entry into the cells and reduced proliferation of the cells. The reduction in cell proliferation was also part of the protective effect, because inhibiting proliferation with specific pharmacological agents, instead of D-lactic acid, also protected cultured epithelial cells from infection.
Intriguingly, the protective effect happened rapidly. The epithelial cells were protected after only 30 minutes of exposure to medium containing D-lactic acid produced by the protective bacteria. The protection lasted a long time (24 hours). Thus, the data indicated that transient changes in the vaginal microbiome can have long-lasting effects on the susceptibility to sexually transmitted infections.
Conditions that promote the growth of bacteria that produce L-lactic acid rather than the bacteria that produce D-lactic acid would increase susceptibility to infection. One of the conditions that increased the L-lactic acid-producing bacteria was an antibiotic azithromycin, which used as a primary treatment for chlamydial infection. This antibiotic-induced change in the vaginal microbome may explain the high rate of recurrence in patients and suggests that combining that azithromycin with some form of vaginal probiotic may be beneficial. Vaginal probiotics are not yet available. So another option would be to use other antibiotics, such as doxycycline, that do not impair growth of the protective bacteria for treatment.
“We will now be able to leverage these microbiomes to identify women at risk of infections, but more importantly to develop improved strategies to restore an optimal protection when it is lacking. Unlike our genes, the vaginal microbiome can be modulated to increase protection against chlamydia, but also against other sexually transmitted infections, including HIV,” said Dr. Ravel of the research. Chlamydial infection and other sexually transmitted diseases influence the health of the infected individuals and woman’s fertility. Thus, these results are important for understanding the interplay between the vaginal microbiome and multiple aspects of reproductive health.
Research into the human microbiome has led to the creation of new companies, such Seed Health, Inc., which strives to leverage knowledge of the human microbiome to develop products that improve health and wellness. Indeed, Dr. Ravel, the corresponding author of the study, is a researcher at the University of Maryland School of Medicine, a member of the Scientific Advisory Board of Seed Health, and has launched a company supported by Seed Health called LUCA Biologics to develop “living medicines targeting the vaginal microbiome.” Lactin-V is a vaginal probiotic by OSEL that is currently in a clinical trial for recurrent vaginosis.
V. L. Edwards, et al., The cervicovaginal microbiota-host interaction modulates Chlamydia trachomatis infection. mBio 10, e01548–19 (2019). DOI: 10.1128/mBio.01548–19
N. R. Gough, Antibiotic treatment reshapes the vaginal microbiome. BioSerendipity (19 August 2019). https://www.bioserendipity.com/antibiotic-treatment-reshapes-the-vaginal-microbiome/