ESTRO 2025 - Abstract Book

S3941

Radiobiology - Normal tissue radiobiology

ESTRO 2025

Furthermore, relying solely on stool sampling neglects the spatial variance of microbial abundance and composition along the gastrointestinal tract known as gut biogeography. We sought to develop a non-invasive, clinically-mimetic, focal bowel irradiation model to assess microbiome dynamics in both the duodenum and the stool after high-dose duodenal irradiation. Material/Methods: Male and female C57BL/6 mice (N=8-10/group/time point) underwent sham computed tomography or focal irradiation to 12 or 18 Gy delivered to the proximal duodenum with a small animal irradiator. Oral iodine contrast enabled bowel visualization. Stool samples were collected at days 4, 14, or 91 post-treatment. Subsets of mice were sacrificed at days 4, 14 or 91 and duodenal samples were harvested. Genomic DNA was extracted from stool and duodenal tissue homogenates and processed for Illumina sequencing of the V3-V4 region of the 16S rRNA gene. Taxonomy was assigned using the DADA2 package in R. MaAsLin2 was used to identify bacterial taxa associated with radiotherapy. Results: One hundred percent of mice survived until the planned time of sacrifice. Analysis of 16S data revealed distinct microbial communities in the duodenum and stool. Focal duodenal irradiation led to dose-dependent changes in alpha and beta diversity in the duodenum but not the stool. Multivariable association modeling with MaAsLin2 identified dose-dependent microbiome perturbations relative to sham controls at days 4 and 14 post-treatment in the duodenum involving 5 genus and 6 family taxonomic groups. Notably, there was an increase Akkermansiaceae family at days 4 (p<0.01) and 14 (p<0.01) post-treatment and Lactobacillaceae family at day 4 (p<0.05) in the mice irradiated to 18 Gy. Only one significant change was observed in the stool of irradiated mice, an increase in lactobacillus genus/family at day 14 in the 18 Gy group (p<0.001).