Recurrent Implantation Failure and the Gut–Endometrium Axis: A Pilot Study on Microbiota Crosstalk

Objective: We aim to assess gut and endometrial microbiota simultaneously in women with unexplained recurrent implantation failure (RIF) and explore the hypothesis of a gut–endometrium microbial axis. Study design: This monocentric observational pilot study included women aged 38 years or younger with a history of RIF. Paired fecal and endometrial samples were collected on the same day and analyzed by 16S rRNA gene sequencing. Relative abundances of major phyla and alpha-diversity indices were compared between compartments. Results: Twenty-one women were included. Chronic endometritis was documented through hysteroscopy in all cases. Gut dysbiosis was observed in 20/21 patients (95.2%), whereas endometrial dysbiosis was found in 16/21 (76.2%); crude agreement between compartments was 71.4% (Gwet’s AC1 0.62, 95% CI 0.25–0.90). The intestinal microbiota was dominated by Bacteroidetes (52.8% ± 14.9%) and Firmicutes (33.3% ± 11.0%), whereas the endometrial microbiota was enriched in Firmicutes (64.5% ± 33.5%) and Proteobacteria (30.9% ± 32.3%). Bacteroidetes were significantly more abundant in fecal than endometrial samples (p < 0.001), while Firmicutes were significantly enriched in the endometrium (p = 0.001). All alpha-diversity indices were significantly higher in feces, indicating greater microbial richness and complexity in the gut. Conclusions: In this pilot cohort of women with unexplained RIF, gut and endometrial dysbiosis frequently co-occurred. These findings support a potential gut–endometrium microbial axis and highlight the possible interplay between gut and endometrial microbiota in recurrent implantation failure. Further studies are warranted to better elucidate the clinical and biological implications of this relationship.