Reports on bacteria detected in maternal fluids during pregnancy are typically associated with adverse consequences, and whether the female reproductive tract harbours distinct microbial communities beyond the vagina has been a matter of debate. Here we systematically sample the microbiota within the female reproductive tract in 110 women of reproductive age, and examine the nature of colonisation by 16S rRNA gene amplicon sequencing and cultivation. We find distinct microbial communities in cervical canal, uterus, fallopian tubes and peritoneal fluid, differing from that of the vagina. The results reflect a microbiota continuum along the female reproductive tract, indicative of a non-sterile environment. We also identify microbial taxa and potential functions that correlate with the menstrual cycle or are over-represented in subjects with adenomyosis or infertility due to endometriosis. The study provides insight into the nature of the vagino-uterine microbiome, and suggests that surveying the vaginal or cervical microbiota might be useful for detection of common diseases in the upper reproductive tract.

Endometriosis (EMS) is a multifactorial disease that affects 10%-15% women of reproductive age and is associated with chronic pelvic pain and infertility. The pathogenesis of EMS has not been consistently explained until now. In this study, we involved 36 endometriosis patients and 14 control subjects who performed laparoscopic surgery due to gynecological benign tumor. The samples from lower third of vagina (CL), posterior vaginal fornix (CU), cervical mucus (CV), endometrium (ET) and peritoneal fluid (PF), were collected and sequenced by 16S rRNA amplicon. The continuous change of the microbiota distribution was identified along the reproductive tract. The flora in lower reproductive tract (CL, CU) were dominated by Lactobacillus. Significant difference of the community diversity began showing in the CV of EMS patients and gradually increased upward the reproductive tract. It indicates the microbiota in cervical samples is expected to be an indicator for the risk of EMS. This study also highlights the decreasing of Lactobacillus in vaginal flora and the increasing of signature Operational Taxonomic Units (OTUs) in transaction zone (CV) and upper reproductive tract (ET, PF) of EMS patients, which reflect the alteration of microbial community associated with EMS, participation of specific colonized bacteria in the EMS pathogenesis and relationship between microbiota and development of disease.

BackgroundThe human uterus is traditionally believed to be sterile, while the vaginal microbiota plays an important role in fending off pathogens. Emerging evidence demonstrates the presence of bacteria beyond the vagina. However, a microbiome-wide metagenomic analysis characterizing the diverse microbial communities has been lacking.ResultsWe performed shotgun-sequencing of 52 samples from the cervical canal and the peritoneal fluid of Chinese women of reproductive age using the Illumina platform. Direct annotation of sequencing reads identified the taxonomy of bacteria, archaea, fungi and viruses, confirming and extending the results from our previous study. We replicated our previous findings in another 24 samples from the vagina, the cervical canal, the uterus and the peritoneal fluid using the BGISEQ-500 platform revealing that microorganisms in the samples from the same individuals were largely shared in the entire reproductive tract. Human sequences made up more than 99% of the 20GB raw data. After filtering, vaginal microorganisms were well covered in the generated reproductive tract gene catalogue, while the more diverse upper reproductive tract microbiota would require greater depth of sequencing and more samples to meet the full coverage scale.ConclusionsWe provide novel detailed data on the microbial composition of a largely unchartered body site, the female reproductive tract. Our results indicated the presence of an intra-individual continuum of microorganisms that gradually changed from the vagina to the peritoneal fluid. This study also provides a framework for understanding the implications of the composition and functional potential of the distinct microbial ecosystems of the female reproductive tract in relation to health and disease.

These data indicate CCL19/CCR7 contributes to proliferation and invasion of ESCs, which are conducive to the pathogenesis of endometriosis through activating PI3K/Akt pathway.

Background Chronic endometritis (CE) is a disease of continuous and subtle inflammation occurring in the endometrial stromal area, which is often asymptomatic or present with non-specific clinical symptoms. Methods This study investigated the composition and distribution of the intrauterine microbiota of 71 patients who underwent hysteroscopy during the routine clinical inspection of infertility. Among them, patients who were diagnosed with chronic endometritis (CE) were allocated into CE group (n = 29) and others into non-CE group (n = 42). There was no significant difference in average age between the two groups (P = 0.19). Uterine flushing fluid was collected by the self-developed cervical trocar uterine cavity sampler and 16S rRNA sequencing was performed. Results The alpha diversity in the CE group was significantly higher than that in the non-CE group (P < 0.05). Firmicutes (newly named Bacillota) were the dominant phylum in the non-CE group (72.23%), while their abundance was much lower in the CE group (49.92%), but there was no statistically significant difference between the two groups. The abundances of Actinobacteriota and Cyanobacteria in the CE group were significantly higher than those in the non-CE group (P < 0.05). At the genus level, the abundance of Lactobacillus dominated in all samples, which presented a significantly lower abundance in the CE group (40.88%) than that in the non-CE group (64.22%) (P < 0.05). Correspondingly, the abundance of non-Lactobacillus was higher in the CE group, among which Pseudomonas and Cutibacterium increased significantly (P < 0.01). Moreover, compared with the non-CE group, the pathways involved in arginine and proline metabolism and retinol metabolism were significantly enriched in the CE group (P < 0.05), while the metabolism of lipid and prenyltransferases were significantly decreased in the CE group (P < 0.05). Conclusions A certain microbial community was colonized in the uterine cavity, which was dominated by Lactobacillus. The structure and distribution of intrauterine microbiota in the CE group were different from those in the non-CE group by showing a lower abundance of Lactobacillus, and a significantly higher abundance of Pseudomonas and Cutibacterium. Additionally, the microbial metabolism was altered in the CE group. This study elaborated the alteration of intrauterine microbiota in CE patients, which may contribute to the diagnosis of CE and provide a reference for antibiotic treatment of CE.

Human urine is traditionally considered to be sterile, and whether the urine harbours distinct microbial communities has been a matter of debate. Potential links between female urine and reproductive tract microbial communities is currently not clear. Here, we collected urine samples from 147 Chinese women of reproductive age and explored the nature of colonization by 16S rRNA gene amplicon sequencing, quantitative real-time PCR, and live bacteria culture. To demonstrate the utility of this approach, the intra-individual Spearman’s correlation was used to explore the relationship between urine and multiple sites of the female reproductive tract. PERMANOVA was also performed to explore potential correlations between the lifestyle and various clinical factors and urinary bacterial communities. Our data demonstrated distinct bacterial communities in urine, indicative of a non-sterile environment. Streptococcus-dominated, Lactobacillus-dominated, and diverse type were the three most common urinary bacterial community types in the cohort. Detailed comparison of the urinary microbiota with multiple sites of the female reproductive tract microbiota demonstrated that the urinary microbiota were more similar to the microbiota in the cervix and uterine cavity than to those of the vagina in the same women. Our data demonstrate the potential connectivity among microbiota in the female urogenital system and provide insight and resources for exploring diseases of the urethra and genital tract.

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