The discovery of distinct microbial communities along the female reproductive tract from the vagina to fallopian tube, using genetic amplification (amplicon) technology, challenge the traditional view of human fetal development taking place in a sterile environment, a new Chinese study has found.

Published in the Oct. 17, 2017, edition of Nature Communications, the study also showed for the first time that variations in those microbial communities correlate with some uterine-related disorders, potentially serving as biomarkers for gynecologic diseases and enabling a better understanding of their causes and treatment.

"There have been recent reports of bacterial flora in normal placenta, amniotic fluid and even fallopian tube samples, but for various reasons these results have been controversial," lead researcher Huijue Jia, executive deputy director of the Institute of Metagenomics at Beijing Genomic Institute (BGI) in Shenzhen, told BioWorld.

This is the first gene amplicon sequencing study to be performed in healthy young women, together with live culture and quantitative analyses between different sites and sampling routes.

The vagina is known to be the home for many different microorganisms, but the presence of a defined microbiota in the upper reproductive tract of women, in the absence of infection, has previously been less clear.

"This is a significant finding, as it is the first time that the existence of microbiota in the female upper reproductive tract has been brought to attention," Jia said.

The BGI team analyzed microorganisms sampled from six sites along the reproductive tracts of 110 healthy young Chinese women, including the lower vagina, posterior fornix, cervical canal mucus, endometrium, fallopian tubes, and peritoneal fluid from Douglas' pouch.

Consistent with previous reports, they found that Lactobacillus bacteria dominate the lower tract, including the vagina and fornix. However, lactobacilli were progressively replaced in the upper tract by other species such as Pseudomonas. They also cultivated bacteria from the upper tract and showed that live bacteria are also present there.

"This finding has enabled us better to understand the microecologic environment of the female pelvic and reproductive tract," said Jia.

That finding suggests many gynecological diseases are characterized by different degrees of ecological disturbance in the female reproductive tract. Therefore, maintenance of that balance may be an important factor in the prevention and treatment of reproductive system diseases.

"This is of particular significance in terms of comprehensively evaluating the microecology of the reproductive tract in the prevention, treatment and prognosis of reproductive tract-related diseases," she said.

Correlations were also documented between variations in the microbiota and the phase of the menstrual cycle, as well as disorders including benign uterine tumors, adenomyosis (a condition in which the inner lining of the uterus breaks through the uterine wall), and infertility due to endometriosis.

"Vagino-uterine microbiota were seen to vary with several factors, including the menstrual cycle, number of births and gynecologic diseases," Jia noted.

The findings support the idea that live bacteria exist in the female upper reproductive tract and suggest it might be possible to survey the health status of the uterus and peritoneal cavity by microbial analysis of cervical mucosa.

"This opens a new direction for the study of the female reproductive system," said Jia. "It suggests an association between microbes and certain gynecological ailments, such as endometrial cancer and endometriosis, in which tissue normally found inside the uterus grows outside this region."

In the future, further research employing larger and prospective study cohorts will be needed to validate the potential use of cervical microbiota analysis as a biomarker of vaginal and uterine disorders.

"We have found biomarkers of adenomyosis and endometriosis, which provide a new approach to the detection or risk assessment of these diseases and can be used for their early diagnosis. With fewer cases of each disease, more samples [are] needed to verify this in the future," said Jia.

This research can provide an important basis for the study, early diagnosis of and effective intervention in reproductive tract-related diseases.

"While we have identified a potential association between bacteria and uterine-related diseases, we failed to identify a causal link," Jia said. "Addressing this question will be our next step and we are currently conducting further studies of the relationship between diseases and bacteria."