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McCurry, Erin

University of British Columbia

Purpose: Up to 25% of patients receiving thoracic radiotherapy will develop radiation-induced lung injuries (RILI) and while dosimetric factors affect this outcome, individual differences in the intestinal microbiome, which shapes immunity, may also influence the tissue injury response. This thesis examined the intestinal and fecal microbiomes of three mouse strains with distinct RILI phenotypes [Pneum1 = early onset distress, Radpf1 = survive to experimental endpoints, and C57BL/6J = wildtype] to assess bacterial traits as predictive biomarkers of RILI. Methods: Laboratory derived Pneum1 and Radpf1 mice were given 14 Gy whole thorax irradiation at 8 weeks of age. The intestinal contents of these mice and of age matched controls were collected one week post-irradiation. Fecal samples were collected from untreated Pneum1, Radpf1, and C57BL/6J mice at 8 weeks of age. Bacterial rRNA was extracted from 50 intestinal and fecal samples and the V4 region of the 16S rRNA gene was sequenced. rRNA gene sequences were assigned taxonomic labels to reveal the bacterial constituents of the microbiome and their abundances. Bacterial compositions were analyzed at the genus level to identify features which differentiate mice by radiation response and which correlate with the expected strain-dependent post-irradiation survival time. Results: Significant differences in the abundances of bacterial genera Faecalibaculum (p<0.0001) and Romboutsia (p=0.0008) were identified in the intestinal microbiome of Pneum1 and Radpf1 mice. In the fecal microbiome ASF356, Tyzzerella, and an uncultured Christensenellaceae genus were differentially abundant in Pneum1 and Radpf1 mice (p=0.0003, p=0.0002, p<0.0001). 1 week after thoracic irradiation, a significant change in the composition of the intestinal microbiome of Pneum1 (p=0.042, R2=0.211), but not Radpf1 (p=0.11, R2=0.139), mice was observed. Linear regression of bacterial abundance with post-irradiation survival time revealed intestinal microbiome Romboutsia levels correlated with expected post-irradiation survival time in control (R= -0.77, p=0.0005) and irradiated mice (R= -0.82, p<0.0001). Conclusion: The bacterial genus Romboutsia in the intestinal microbiome differentiated mice by RILI phenotype and correlated with survival from RILI, and therefore is a potential predictive biomarker of RILI.

Text

2024-08-16

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/88959

Medical Physics

University of British Columbia

UBCO

http://creativecommons.org/licenses/by-nc-nd/4.0/