Adaptive changes in the gut microbiome during standard-of-care chemoradiotherapy for gynecologic cancers

El Alam, M. B.; Sims, T. T.; Kouzy, R.; Biegert, G.; Abi Jaoude, J.; Karpinets, T.; Court, K. Y.; Wu, X.; Medrano, A. D.; Mezzari, M.; Ajami, N.; Solley, T.; Ahmed-Kaddar, M.; Lin, L.; Ramondetta, L.; Jazaeria, A.; Jhingran, A.; Eifel, P.; Schmeler, K.; Wargo, J.; Klopp, A.; Colbert, L.

doi:10.1101/2020.04.10.036426

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bioRxiv · 10.1101/2020.04.10.036426

Adaptive changes in the gut microbiome during standard-of-care chemoradiotherapy for gynecologic cancers

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Abstract

BackgroundA diverse and abundant gut microbiome can improve cancer patients treatment response; however, the effect of pelvic chemoradiotherapy (CRT) on gut diversity and composition is unclear. The purpose of this prospective study was to identify changes in the diversity and composition of the gut microbiome during and after pelvic CRT. Materials and MethodsRectal swabs from 58 women with cervical, vaginal, or vulvar cancer from two institutions were prospectively analyzed before CRT (baseline), during CRT (weeks 1, 3, and 5), and at first follow-up (week 12) using 16Sv4 rRNA gene sequencing of the V4 hypervariable region of the bacterial 16S rRNA marker gene. Observed operational taxonomic units (OTUs; representative of richness) and Shannon, Simpson, Inverse Simpson, and Fisher diversity indices were used to characterize alpha (within-sample) diversity. Changes over time were assessed using a paired t-test, repeated measures ANOVA, and linear mixed modeling. Compositional changes in specific bacteria over time were evaluated using linear discriminant analysis effect size. ResultsGut microbiome richness and diversity levels continually decreased throughout CRT (mean Shannon diversity index, 2.52 vs. 2.91; all P <0.01), but were at or near baseline levels in 60% of patients by week 12. Patients with higher gut diversity at baseline had the steepest decline in gut microbiome diversity. Gut microbiome composition was significantly altered during CRT, with increases in Proteobacteria and decreases in Clostridiales, but adapted after CRT, with increases in Bacteroides species. ConclusionAfter CRT, the gut microbiomes diversity tends to return to baseline levels, but its structure and composition remain significantly altered. These changes should be considered when designing studies to analyze the gut microbiome as a predictive or prognostic biomarker in patients who receive pelvic CRT for gynecologic cancers.

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El Alam, M. B., Sims, T. T., Kouzy, R., Biegert, G., Abi Jaoude, J., Karpinets, T., Court, K. Y., Wu, X., Medrano, A. D., Mezzari, M., Ajami, N., Solley, T., Ahmed-Kaddar, M., Lin, L., Ramondetta, L., Jazaeria, A., Jhingran, A., Eifel, P., Schmeler, K., Wargo, J., Klopp, A., Colbert, L.. 2020-04-12. Adaptive changes in the gut microbiome during standard-of-care chemoradiotherapy for gynecologic cancers. https://doi.org/10.1101/2020.04.10.036426

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