ABSTRACT
Background A 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 Methods Rectal 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.
Results Gut 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.
Conclusion After CRT, the gut microbiome’s 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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵+ Shared corresponding Authorship
Conflicts of Interest: The authors report no conflicts of interest.
Financial Support: This research was supported in part by the Radiological Society of North America Resident/Fellow Award (to L.E.C.); by the National Institutes of Health (NIH) through MD Anderson’s Cancer Center Support Grant P30CA016672 and through T32 grant CA101642-14 (T.T.S.); and by The University of Texas MD Anderson Cancer Center HPV-related Cancers Moonshot (L.E.C., A.K.). The funding sources were not involved in the development of the research hypothesis, study design, data analysis, or manuscript writing. Data access was limited to the authors of this manuscript.
Condensation: The gut microbiome changes significantly during pelvic chemoradiation, which should be considered in future studies.
AJOG at a Glance:
Why was this study conducted? To determine changes in gut microbiome associated with treatment of gynecologic cancers
What are the key findings? The gut microbiome changes significantly during treatment, and variably returns to baseline. Approximately 2/3 of patients return to or near their baseline gut diversity, while 1/3 remain significantly less diverse. The composition of nearly all patients’ guts is significantly different after CRT.
What does this study add to what is already known? This study reports the largest cohort of serial sequencing before, during and after CRT to inform future studies.