Gut Microbiome During and after Pelvic Chemoradiation for Gynecologic Cancers

Abstract

There is significant interest in the gut microbiome and its role in cancer response, with previous data showing that a more diverse and abundant gut microbiota can lead to improved response; however, the effect of radiation on gut diversity and composition complicates interpretations in the setting of radiation therapy. The purpose of this study was to prospectively describe the landscape of the gut microbiome during and after pelvic chemoradiation therapy (CRT) for patients with cervical, vaginal, or vulvar cancer. Anorectal swabs from 58 women with cervical, vaginal, or vulvar cancer from two institutions were prospectively analyzed at baseline, during CRT (weeks 1, 3, and 5), and at first follow up (week 12) using 16Sv4 rRNA gene sequencing. Observed OTUs, Shannon, Simpson, Inverse Simpson, and Fisher diversity indices were used to characterize Alpha (within sample) diversity. Changes over time were assessed using paired t-test to baseline, repeated measures ANOVA, and linear mixed modeling. Changes in specific bacteria were evaluated using linear discriminant analysis effect size (LEfSe) to identify bacterial genera that were differentially enriched in patients at baseline, week 5, and week 12. Gut microbiome diversity declined gradually over the course of treatment, reaching significance at week 5 (Shannon: 2.52 vs. 2.91; all P <0.01); however, the gut microbiome tends to return to baseline after treatment (week 12; 34.3% of patients). Patients with higher diversity at baseline have a steeper decrease in their gut microbiome diversity over time (Shannon: Slope = -0.81; all P <0.01). The relative abundance of the Clostridia class decreased over time (27.1% - 19.3%), while individual OTUs of Clostridia both increased and decreased over time (69.7%-38%). During CRT, patients’ gut microbiome diversity levels decreased but generally returned to baseline after treatment and varied by baseline diversity. Although patients’ gut microbiome diversity tends to return to baseline levels after treatment completion, the structure of their microbiomes may be affected for a longer period of time. These serial changes in the gut microbiome during CRT should be considered when designing studies to analyze the gut microbiome effects on treatment response and toxicity.