Scientists have long known that in healthy humans, a diverse universe of microbes exists in the vagina. But the existence of bacteria in women’s upper reproductive tract, which includes the uterus and fallopian tubes, remains controversial. A new study, published today (October 17) in Nature Communications, reports that even in the absence of infection, distinct communities of microbes live in these areas.
“The question about whether there are bacteria in the reproductive tract has been on the table for several years at least,” says Larry Forney, a microbiologist at the University of Idaho who was not involved in the work. “I think it’s a pretty strong study, and I think people will take it for what it is, which is a good, initial effort.”
Prior to this study, evidence of bacteria in the female upper reproductive tract was scarce, study co-author Ruifang Wu, a physician and professor at Peking University Shenzhen Hospital, writes in an email to The Scientist. There were hints, she adds—some researchers have suggested a link between microbes and certain gynecological ailments, such as endometrial cancer and endometriosis, in which tissue normally found inside the uterus grows outside this region.
To address the question of whether microorganisms are present in these parts of the female body, Wu and her colleagues collected samples from the reproductive tracts of 110 women who were undergoing surgery for various conditions not associated with infections, such as fibroids and endometriosis. This allowed the team to circumvent one of the main issues with examining upper regions of the genital tract, which is that in order to retrieve these samples, researchers typically need to go through the vagina and cervix—a process that can easily lead to contamination.
The researchers then used a ribosomal RNA (rRNA) sequencing method that allowed them to identify distinct bacterial communities and their relative abundance in areas of the lower reproductive tract, such as the vagina and cervix, and upper regions, which include the fallopian tubes and endometrium, which lines the uterus. They found that lower regions were dominated by Lactobacillus, which scientists have identified in prior studies. However, the abundance of this species decreased in higher regions, which housed more diverse microbial populations.
According to Wu, the team thinks that Lactobacillus was more abundant in the lower reproductive tract because the dominance of this species depressed the growth of other kinds of bacteria. Less Lactobacillus in the upper reproductive tract then gave other taxa the chance to grow.
Her team also reported differences in the microbial composition of the reproductive tracts between individuals with and without certain conditions, such as endometriosis-associated infertility.
Caroline Mitchell, a reproductive biologist at Massachusetts General Hospital who did not take part in this research, says that this study confirms her previously published findings of bacteria in the uterus. However, she adds, “anytime folks do 16S [rRNA gene amplicon] sequencing on low biomass samples, I'm always super skeptical.” Specially, she explains, when the sequencing method Wu’s group used is applied to areas believed to contain a low number of microbes—such as the upper reproductive tract—it is more likely to pick up bacterial contaminants.
Wu’s team did take steps to control for contamination, such as sampling the surgeon’s gloves, patients’ skin, and the materials such as water and swabs used to conduct the experiments. Despite these measures, “I don't totally feel like they allayed my skepticism,” Mitchell adds. “A lot of the bacteria that they found [in the upper reproductive tract] are taxa more commonly found in water and soil, which suggests to me that some of them are contaminants.”
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Another key limitation of this study, according to Jacques Ravel, a microbiologist at the University of Maryland not involved in the work, is that all the women in this study were not completely healthy, given that they all required surgery for some condition. “They did a lot of analytical work, but to me, there’s still a big question mark about the presence of healthy microbiota in the upper genital tract,” he says.
Ravel adds that the authors’ link to uterine-related diseases is premature. “The burden of proof [for this claim] is super high,” he tells The Scientist. “A lot of people walk a very fine line in some of those papers where they suggest a causative link between the microbe and the disease, forgetting that it could be [the disease that] causes the change in microbes.”
Wu agrees that while this study pointed to a potential association between bacteria and uterine-related diseases, it was unable to identify a causal link. Addressing this question will be the next step for her team. “Based on our findings, we are conducting further studies [to investigate] the relationship of gynaecological and obstetric diseases and bacteria,” she writes.