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Influence of neo-adjuvant radiotherapy on the intestinal microbiota of rectal cancer patients

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Abstract

Purpose

Neo-adjuvant radiotherapy (NART) is a widely used pre-surgery radiotherapy for rectal cancer patients. Although NART is effective in reducing tumor burden before surgery, it may cause dysbiosis of intestinal microbiota. The intestinal microbiota shapes tumor inflammatory environment and influences cancer progression. However, how NART remodels the microbiota and how the microbiota affects therapeutic efficacy has been largely elusive. This study aimed to reveal the details of how NART affects the intestinal microbiota in patients with rectal cancer.

Methods

Rectal cancer patients who received NART were recruited into the study, and their healthy family members on the same diet served as controls. Stool samples from five rectal cancer patients (28 in total) and five healthy individuals (16 in total) were collected for intestinal microbiota analysis by 16S rRNA gene amplicon sequencing. Samples from patients were divided into earlier- and later-NART according to the number of NART.

Results

NART did not significantly affect the α diversity of intestinal microbiota. However, the abundance of bacterial genera associated with cancer progression tended to decrease in later-NART patients. More importantly, a variety of oral pathogenic bacteria were enriched in the intestine of later-NART patients. NART also affected functional pathways associated with the microbiota in DNA repair, metabolism, and bacterial infection.

Conclusion

NART significantly altered the microbiota composition and function in rectal cancer patients, and some oral pathogens were found to translocate to the intestine. This is the first report to study the effect of NART on intestinal microbiota in patients with rectal cancer, exploring the importance of intestinal microbiota during the process of NART.

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Data availability

Contact the corresponding author for the raw sequencing reads.

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Acknowledgements

This research was funded by the Health Commission of Hubei Province (WJ2021M193), the Biomedical Center of Hubei Cancer Hospital (2022SWZX13), Natural Science Foundation of Hubei Province (2016CFB405), Health and Family Planning Commission of Hubei Province (WJ2017M144), and the Fundamental Research Funds for the Central Universities (2662017PY112).

Funding

This research was funded by the Health Commission of Hubei Province (WJ2021M193), the Biomedical Center of Hubei Cancer Hospital (2022SWZX13), Natural Science Foundation of Hubei Province (2016CFB405), Health and Family Planning Commission of Hubei Province (WJ2017M144), and the Fundamental Research Funds for the Central Universities (2662017PY112).

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Contributions

SX: data curation; formal analysis; investigation; methodology; visualization; roles/writing—original draft. QL: data curation; formal analysis; investigation; methodology; resources; writing—review and editing. NZ: conceptualization; formal analysis; funding acquisition; resources; writing—review and editing. YZ: investigation; methodology; writing—review and editing. JZ: conceptualization; funding acquisition; project administration; resources; writing—review and editing. QT: conceptualization; data curation; formal analysis; project administration; writing—review and editing. S-HC: writing—review and editing. LL: funding acquisition; formal analysis; project administration; writing—review and editing. JH: conceptualization; formal analysis; funding acquisition; project administration; writing—review & editing. All authors read and approved the final manuscript.

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Correspondence to Li Lu or Jin He.

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This is certify that the design and methods of the research are in accordance with the requirements of related regulations and procedures as well as the ethical principles, and approved by the Institutional Review Board of Hubei Cancer Hospital, project associated code LLHBCH2022YN-044.

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Informed consent was obtained from all subjects involved in the study.

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Xu, S., Lv, Q., Zou, N. et al. Influence of neo-adjuvant radiotherapy on the intestinal microbiota of rectal cancer patients. J Cancer Res Clin Oncol 149, 6085–6096 (2023). https://doi.org/10.1007/s00432-022-04553-6

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