Modulating the Gut Microbiota via Rectal Ozone Insufflation in Gynecological Cancer Patients with Radiotherapy/Chemotherapy-Induced Pelvic Toxicity: A Proposed Clinical Study Protocol
This manuscript proposes a clinical study to evaluate the impact of rectal OT on the gut microbiota of patients with gynecological cancers and chronic R/CIPT. Proposed Methods: A prospective, observational study of 38 patients is outlined: 19 with CTCAE v5.0 Grade ≥2 chronic R/CIPT receiving compassionate rectal OT (~40 sessions over 4 months), and 19 matched controls without toxicity. Stool samples for 16S rRNA sequencing will be collected from the OT group pre- and post-intervention and once from controls. Primary endpoints are changes in microbiota composition/diversity and pelvic toxicity scores (CTCAE v5.0, EORTC QLQ-CX24). Secondary endpoints include quality of life (EORTC QLQ-C30, EQ-5D-5L), anxiety/depression (HADS), and serum inflammatory/oxidative stress biomarker analysis. Anticipated Results and Conclusion: This will be the first study to prospectively investigate whether rectal OT's effect correlates with a beneficial shift in the gut microbiota, specifically an increase in commensals (e.g., short-chain fatty acids producers) and a decrease in pathobionts. If successful, OT could be assessed as a novel, microbiota-targeting intervention for R/CIPT. The findings from this pilot study will provide the necessary groundwork for a future randomized controlled trial to definitively establish causality and efficacy.
Authors
- Gregorio Martı́nez-Sánchez (ORCID: https://orcid.org/0000-0002-6628-7388)
- Ángeles Cánovas-Molina (ORCID: https://orcid.org/0000-0001-8557-860X)
- M Zajac (ORCID: https://orcid.org/0009-0003-3870-2382)
- Francisco Rodrı́guez-Esparragón (ORCID: https://orcid.org/0000-0003-1663-3673)
- María Fernández-Tagarro
- Ignacio J. Jorge (ORCID: https://orcid.org/0000-0001-7178-5691)
- José Enrique Piñero (ORCID: https://orcid.org/0000-0001-6233-8224)
- Elizabeth Córdoba-Lanús (ORCID: https://orcid.org/0000-0001-5534-8280)
- Jesús M. González‐Martín (ORCID: https://orcid.org/0000-0001-6816-4157)
- Bernardino Clavo (ORCID: https://orcid.org/0000-0003-2522-1064)
- Mario Federico (ORCID: https://orcid.org/0000-0002-6184-9070)
- Avinash Ramchandani (ORCID: https://orcid.org/0000-0002-9754-3903)
- Juan Antonio Díaz-Garrido (ORCID: https://orcid.org/0000-0001-9713-8177)
- Ruth Martín-Alfaro
- Minerva Navarro
- Ana M. Vargas-Prado (ORCID: https://orcid.org/0009-0003-5399-9831)
- Ivone Maria Ribeiro
- Jacob Lorenzo-Morales (ORCID: https://orcid.org/0009-0008-1736-0471)
Institutions
- Universidad de Las Palmas de Gran Canaria (ES)
- Universidad de La Laguna (ES)
- Hospital Universitario Insular de Gran Canaria (ES)
- Instituto de Salud Carlos III (ES)
- Universidad Fernando Pessoa Canarias (ES)
- Hospital Universitario de Gran Canaria Doctor Negrín (ES)
- Ospedali Riuniti di Ancona (IT)
- Centro de Investigación Biomédica en Red (ES)
- Fundación Canaria de Investigación Sanitaria (ES)
- Spanish Ovarian Cancer Research Group (ES)
Publication Details
- Journal
- Journal of Clinical Medicine
- Published
- 2025-11-12
- DOI
- https://doi.org/10.3390/jcm14228015
- Primary Topic
- Medical and Biological Ozone Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministerio de Ciencia e Innovación
- Instituto de Salud Carlos III