Assessing the female urogenital-rectal axis microbiome: focus on endometriosis and recurrent implantation failure

Emerging evidence suggests microbial dysbiosis may contribute to gynaecological pathologies, including endometriosis and recurrent implantation failure (RIF). The vaginal microbiome is well-characterised, with Lactobacillus-dominance as a hallmark of health, yet interactions between vaginal, cervical, and endometrial microbiomes remain inconclusive. The adjacent sites to the vagina, rectal and urinary environments in infertile women are scarcely studied.

This cross-sectional study included 136 reproductive-aged women, enrolled at the Reproductive Unit of the University Hospital Virgen de las Nieves (Granada, Spain) between March 2019 and March 2024. Each participant provided five samples during the mid-secretory phase: vaginal and cervical swabs, endometrial brushing, urine, and rectal swabs. The microbiome was analysed using 16S rRNA gene sequencing (V4 region) with functional profiles inferred using PICRUSt2. Diversity and bacterial abundance were compared between endometriosis, RIF, and controls, adjusting for age, body mass index, and antimicrobial use.

In total, 520 samples from 104 women were analysed and revealed shared microbial profiles across the vagina, cervix, endometrium, and urine. The rectal microbiome differed significantly from urogenital sites (Global PERMANOVA, adj p-value = 0.001, R² = 0.259). A Lactobacillus gradient in the reproductive tract was observed, with dominance > 98% in the lower tract, 69.72% in urine, and 46.25% in the endometrium. Moreover, Lactobacillus negatively correlated with all other genera within the reproductive tract. Significant differential abundance was detected between body sites: 15 bacteria between vagina-cervix, 166 vagina-uterus and 172 cervix-uterus (all adj p-values < 0.05). Diversity comparisons between the condition groups (endometriosis and RIF) and controls at each anatomical sites revealed no significant differences in microbial communities and functional pathways. However, four bacterial genera showed a significantly different abundance between the endometriosis and controls in the vagina.

Our study results provide knowledge about the microbial composition throughout the female urogenital tract and rectum, highlighting the interindividual variability rather than the site-specificity. The vaginal bacteria that associated with endometriosis should be investigated further for clarifying their potential as non-invasive biomarkers of the disease. Microbiomes of other urogenital sites do not seem to associate with endometriosis, and microbiomes of the urogenital-rectal axis do not seem to correlate with RIF.

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