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Peer-reviewedCC BYJournal of clinical medicine

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

  1. 1Department of Public Health, School of Medicine, University of Naples “Federico II”, 80131 Naples, Italy
  2. 2AMES Centro Polidiagnostico Strumentale, 80013 Naples, Italy

Abstract

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.

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BibTeX
@article{caruso2026recurrent,
  title = {{Recurrent Implantation Failure and the Gut–Endometrium Axis: A Pilot Study on Microbiota Crosstalk}},
  author = {Flora Caruso and Luigi Vigilante and Danilo Borrelli and Alessandra Gallo and Ida Strina and Attilio Di Spiezio Sardo and Maria Rosaria Fantuz and Giovanni Savarese},
  journal = {Journal of clinical medicine},
  year = {2026},
  month = oct,
  doi = {10.3390/jcm15197620},
  url = {https://europepmc.org/article/PMC/PMC13666214},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Recurrent Implantation Failure and the Gut–Endometrium Axis: A Pilot Study on Microbiota Crosstalk
AU  - Flora Caruso
AU  - Luigi Vigilante
AU  - Danilo Borrelli
AU  - Alessandra Gallo
AU  - Ida Strina
AU  - Attilio Di Spiezio Sardo
AU  - Maria Rosaria Fantuz
AU  - Giovanni Savarese
PY  - 2026
DA  - 2026/10/01
JO  - Journal of clinical medicine
DO  - 10.3390/jcm15197620
UR  - https://europepmc.org/article/PMC/PMC13666214
AB  - 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.
SN  - 2077-0383
ER  -