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

J Cancer Res Clin Oncol. 2023 Aug;149(9):6085-6096. doi: 10.1007/s00432-022-04553-6. Epub 2023 Jan 19.

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.

Keywords: 16S rRNA gene high-throughput sequencing; Intestinal microbiota; Radiotherapy; Rectum; Therapeutic efficacy.

MeSH terms

  • Bacteria
  • Feces
  • Gastrointestinal Microbiome*
  • Humans
  • RNA, Ribosomal, 16S / genetics
  • Radiotherapy, Adjuvant
  • Rectal Neoplasms* / radiotherapy

Substances

  • RNA, Ribosomal, 16S