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

doi:10.1016/j.radonc.2023.109950

Microbiome and metabolome dynamics during radiotherapy for prostate cancer

Radiother Oncol. 2023 Dec:189:109950. doi: 10.1016/j.radonc.2023.109950. Epub 2023 Oct 10.

Authors

Willeke Danckaert¹, Mathieu Spaas², Nora Sundahl³, Aurélie De Bruycker⁴, Valérie Fonteyne², Ellen De Paepe⁵, Carlos De Wagter⁶, Lynn Vanhaecke⁷, Piet Ost⁸

Affiliations

¹ Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium. Electronic address: Willeke.Danckaert@UGent.be.
² Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium.
³ Department of Radiation Oncology, AZ Groeninge Kortrijk, Kortrijk, Belgium.
⁴ Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium; Department of Radiation Oncology, AZ Groeninge Kortrijk, Kortrijk, Belgium.
⁵ Laboratory of Integrative Metabolomics (LIMET), Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium.
⁶ Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium.
⁷ Cancer Research Institute Ghent (CRIG), Ghent, Belgium; Laboratory of Integrative Metabolomics (LIMET), Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium; Institute for Global Food Security, School of Biological Sciences, Queen's University, BT7 1NN Belfast, United Kingdom.
⁸ Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium; Department of Radiation Oncology, Iridium Netwerk, Wilrijk, Belgium.

PMID: 37827280
DOI: 10.1016/j.radonc.2023.109950

Abstract

Background: 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.

Material & methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Metabolome; Microbiota; Prospective studies; Prostatic Neoplasms; Radiotherapy.

MeSH terms

Humans
Male
Metabolome
Prospective Studies
Prostate / radiation effects
Prostatic Neoplasms* / radiotherapy
RNA, Ribosomal, 16S

Substances

RNA, Ribosomal, 16S