Impact of curative pelvic radiotherapy on the gut environment of prostate cancer patients

Abstract

[Background] Gastrointestinal symptoms are frequent after pelvic radiotherapy and can greatly affect the quality of life of cancer survivors. The effect of radiation on the intestinal microbiome, and the implications of a radiotherapy-induced dysbiosis and the derived intestinal inflammation have received very little attention. [Aim] To perform a follow-up study in patients with prostate cancer for investigating alterations in gut microbiota and metabolites induced by pelvic radiotherapy and associations with inflammation and dietary changes. [Methods] Fourteen patients with prostate cancer undergoing pelvic radiotherapy were recruited and followed during the anti-cancer treatment until two months after finishing. Four stool samples were collected from each patient and changes in the bacterial communities were investigated by sequencing the V3-V4 region of the 16S rRNA gene with Illumina Technology (Miseq PE250), meanwhile short chain fatty acids (SCFAs) were analysed by gas chromatography. Additionally, calprotectin levels were determined using an ELISA kit and, evaluation of dietary intake was recorded by means of semi quantitative food frequency questionnaires. [Results] The composition of the gut communities changes along the radiation treatment, being the Bacteroidetes, the group more affected (p= 0.008, Wilcoxon test). Total SCFAs in feces was reduced with pelvic radiation. In particular, statistical differences were observed for butyrate and acetate excretion with respect to basal time. On the contrary, fecal calprotectin increased significantly during radiotherapy (p= 0.016). In addition, statistical differences in the energy intake were observed before and after two months of radiotherapy. Conclusions: An impact of pelvic radiotherapy on gut microbiota composition and metabolites was observed in prostate cancer patients. Intestinal inflammation occurs at the same time that the microbiome shifts. The effect of radiation was partially, but not completely, restored after two months of finishing the anti-cancer therapy, with changes in the food ingestion patterns still noticeable at this time point.