Microbiome and metabolome dynamics during radiotherapy for prostate cancer

Willeke Danckaert, Mathieu Spaas, Nora Sundahl, Aurélie De Bruycker, Valérie Fonteyne, Ellen De Paepe, Carlos De Wagter, Lynn Vanhaecke, Piet Ost

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Prostate cancer patients treated with radiotherapy are susceptible to acute gastrointestinal (GI) toxicity due to substantial overlap of the intestines with the radiation volume. Due to their intimate relationship with GI toxicity, faecal microbiome and metabolome dynamics during radiotherapy were investigated. This prospective study included 50 prostate cancer patients treated with prostate (bed) only radiotherapy (PBRT) (n = 28) or whole pelvis radiotherapy (WPRT) (n = 22) (NCT04638049). Longitudinal sampling was performed prior to radiotherapy, after 10 fractions, near the end of radiotherapy and at follow-up. Patient symptoms were dichotomized into a single toxicity score. Microbiome and metabolome fingerprints were analyzed by 16S rRNA gene sequencing and ultra-high-performance liquid chromatography hybrid high-resolution mass spectrometry, respectively. The individual α-diversity did not significantly change over time. Microbiota composition (β-diversity) changed significantly over treatment (PERMANOVA p-value = 0.03), but there was no significant difference in stability when comparing PBRT versus WPRT. Levels of various metabolites were significantly altered during radiotherapy. Baseline α-diversity was not associated with any toxicity outcome. Based on the metabolic fingerprint, no natural clustering according to toxicity profile could be achieved. Radiation dose and treatment volume demonstrated limited effects on microbiome and metabolome fingerprints. In addition, no distinctive signature for toxicity status could be established. There is an ongoing need for toxicity risk stratification tools for diagnostic and therapeutic purposes, but the current evidence implies that the translation of metabolic and microbial biomarkers into routine clinical practice remains challenging.
Original languageEnglish
Article number109950
JournalRadiotherapy and Oncology
Volume189
Early online date10 Oct 2023
DOIs
Publication statusPublished - Dec 2023

Keywords

  • Prostatic Neoplasms
  • Radiotherapy
  • Metabolome
  • Microbiota
  • Prospective studies

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