Identification of fallopian tube microbiota and its association with ovarian cancer: a prospective study of intraoperative swab collections from 187 patients
Abstract
Investigating the human fallopian tube (FT) microbiota has significant implications for understanding the pathogenesis of ovarian cancer (OC). In this large prospective study, we collected swabs intraoperatively from the FT and other surgical sites as controls to profile the microbiota in the FT and to assess its relationship with OC. 81 OC and 106 non-cancer patients were enrolled and 1001 swabs were processed for 16S rRNA gene PCR and sequencing. We identified 84 bacterial species that may represent the FT microbiota and found a clear shift in the microbiota of the OC patients when compared to the non-cancer patients. Of the top 20 species that were most prevalent in the FT of OC patients, 60% were bacteria that predominantly reside in the gastrointestinal tract, while 30% normally reside in the mouth. Serous carcinoma had higher prevalence of almost all 84 FT bacterial species compared to the other OC subtypes. The clear shift in the FT microbiota in OC patients establishes the scientific foundation for future investigation into the role of these bacteria in the pathogenesis of ovarian cancer.
SUMMARY
Introduction
Investigating the human fallopian tube (FT) microbiota has significant implications for understanding the pathogenesis of ovarian cancer (OC), pelvic inflammatory disease, and tubal ectopic pregnancy, as well as normal fertilization. Several studies have provided evidence that the FT may not be sterile, but rigorous controls are needed to assess the microbiota in low biomass samples. In this large prospective study, we collected swabs intraoperatively from the FT and other surgical sites as controls to profile the microbiota in the FT and to assess its relationship with OC.
Methods
We collected swabs from the cervix, FT, ovarian surfaces, and paracolic gutters of patients, and from laparoscopic ports and air in the operating room. Surgical indications included known or suspected ovarian cancers, risk-reducing salpingo-oophorectomies due to genetic risk, and benign gynecological disorders. DNA was extracted from the swabs and the bacterial concentrations were quantified using broad-range bacterial quantitative PCR. Bacterial composition was characterized using amplicon PCR targeting the V3–V4 hypervariable region of the 16S rRNA gene combined with next generation sequencing. Multiple negative controls and filtering approaches were used to differentiate FT microbiota from likely contaminant sequences. Presence of the bacterial taxa in both the cervical and FT sample set was required to identify ascending genital tract bacteria.
Results
A total of 81 ovarian cancer patients and 106 non-cancer patients were enrolled and 1001 swabs were processed. The bacterial concentrations of FT and ovarian surfaces averaged 2.5 copies of 16S rRNA genes/μl of DNA (standard deviation, SD 4.6), similar to the paracolic gutter and higher than the controls (p-value < 0.001). We identified 84 bacterial species that may represent the FT microbiota. After ranking the FT bacteria based on the prevalence difference, we found a clear shift in the microbiota of the OC patients when compared to the non-cancer patients. Of the top 20 species that were most prevalent in the FT of OC patients, 60% were bacteria that predominantly reside in the gastrointestinal tract, such asKlebsiella, Faecalibacterium prausnitzii, Ruminiclostridium, andRoseburia, while 30% normally reside in the mouth, such asStreptococcus mitis, Corynebacterium simulans/striatum, andDialister invisus. On the contrary, vaginal bacterial species are more prevalent in the FT from non-cancer patients, representing 75% of the top 20 bacterial species that are most prevalent in non-cancer patients. Serous carcinoma had higher prevalence of almost all 84 FT bacterial species compared to the other OC subtypes.
Conclusion
In this large low biomass microbiota study using intraoperatively collected swabs, we identified a group of bacterial species that appear to reside in the FT across multiple participants. A higher prevalence of some of these bacterial species, especially those that normally reside outside the female genital tract, was noted in the FT from patients with OC, laying the scientific foundation to explore whether these bacteria may have a role in enhancing ovarian cancer risk.
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