Three distinct uterine microbiome community types in healthy women and their interconnection with the vaginal microbiome

Abstract There is no consensus on the composition of the uterine microbiome in healthy women. Bacteria in the uterine cavity engage in reciprocal interactions with endometrial cells and the immune system, thereby maintaining a microecological balance. Given the continuity of the genital tract, the vagina may serve as a potential source of uterine microbiota, which should be included in the investigation. This study aimed to examine the uterine microbiome of healthy women and to provide a reference for further studies. Additionaly, we collected vaginal samples from the same women to compare both niches and investigate the vagina as a potential bacterial source for the uterus. The study cohort consisted of 34 healthy women. We investigated microbiome presence in the uterus by 16S rRNA gene sequence detection. We obtained positive results in all samples analyzed, supporting the hypothesis that the uterus is not a sterile niche. To check bacterial composition, we proceeded with full-length 16S rRNA gene nanopore sequencing. Analysis revealed in the uterus a heterogeneous spectrum of microbial communities, clustering into three distinct community types alongside a single-subject outlier. Among these, Lactobacillus crispatus and Faecalibacterium prausnitzii emerged as the most prevalent taxa. Notably, uterine microbiomes demonstrated greater diversity than corresponding vaginal microbiomes, with overlapping bacterial taxa across both anatomical sites in most individuals, particularly in women with microbial profiles dominated by Lactobacillus species. The uterine microbiome in healthy women is heterogeneous, reflecting considerable inter-individual variability. The presence of shared bacterial taxa between the uterus and vagina within the same individual indicates a connected genital tract microbiome, suggesting potential microbial exchange. These findings highlight the importance of adopting a systemic perspective when investigating the etiology of gynecological pathologies. Future longitudinal studies are necessary to elucidate the selective pressures and dynamics shaping these microbial communities over time.