Feasibility Study Exploring the Effect of Pelvic Radiotherapy on the Intestinal Microbiome and Metabolome to Improve...

Eighty percent patients develop gastrointestinal (GI) symptoms during pelvic radiotherapy. The triggering event is a known enabling identification of pathophysiological changes. The focus of this study was feasibility (identification, recruitment, and retention), however, exploratory microbiome and metabolome analyses were performed.

Patients undergoing pelvic radiotherapy underwent faecal sampling (baseline, week 4, and 6 months), with assessment of GI toxicity using the Imflammatory Bowel Disease Questionnaire (IBDQ) bowel (IBDQB) subset. Participants were split into 2 groups based on IBDQB at week-4. Exploratory analysis was performed to identify differences in metabolome (gas chromatography-mass spectrometry) and microbiome (16s rRNA sequencing).

Two hundred twenty-seven patients were screened, 69 were approached, and 17 were recruited over 18 months (mean age: 61.6 ± 15.3 years; 14 female; 1 withdrawal). Metabolome analysis showed lower heptanal and octanal in baseline samples of patients with higher GI toxicity; lower (methyltrisulfanyl)methane in week-4 samples of patients with higher GI toxicity; and higher butanoic acid and benzaldehyde in month 6 samples in patients with higher GI toxicity. Whole-group microbiome analysis showed a trend towards decreased alpha diversity at 4 weeks; no differences in beta diversity; and a trend towards increase in Lachnoclostridium and decrease in Ruminococcaceae Incertae sedis at week 4. Microbiome analysis split by GI toxicity showed lower alpha diversity for the high GI toxicity group (each timepoint); no significant difference in beta diversity between groups; more genera differentially abundant between the GI toxicity groups at 4 weeks, than at other timepoints.

Recruitment was lower than anticipated. Attrition was low. Exploratory analysis suggests heptanal and octanal may have a role as a biomarker for GI toxicity, and lower alpha diversity may predict GI toxicity, with Lachnoclostridium and Ruminococcaceae Incertae sedis as bacteria of interest.