A prospective study of the adaptive changes in the gut microbiome during standard-of-care chemoradiotherapy for gynecologic cancers

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. 42 of these patients received antibiotics during the study period. 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 diversity of the gut microbiomes in this population tended to return to baseline levels by the 12 week follow-up period, but structure and composition remained significantly altered. These changes should be considered when designing studies to analyze the gut microbiome in patients who receive pelvic CRT for gynecologic cancers.

The Effects of Ionizing Radiation on Gut Microbiota, a Systematic Review

“…Most studies evaluated the effect of ionizing radiation from a medical exposure (pelvic radiotherapy) [ 5 , 7 , 16 , 17 , 18 , 19 , 23 , 26 ], except the study of Sajjadieh et al, who conducted a study to evaluate the gut microbiota changes in 75 rural patients aged between 3 and 18 who lived in a contaminated area at a distance of 60 to 90 km from the Chernobyl Nuclear Power Plant and were exposed to natural environmental radiation and presented abdominal/gastrointestinal symptoms. Additionally, an older method of microbiome analysis, relying on bacterial culture colony-forming units, was used [ 24 ].…”

“…also did not evaluate long-term effects. These are further limitations of these studies, given that the studies that had long-term evaluations reported gradual changes and significant differences in the follow-up sample [5,19,27].…”

“…The three studies that used cultured-based methods could not assess these parameters [23][24][25]. Other parameters such as α-diversity, as measured by Shannon index and Simpson index, also decreased after ionizing radiation exposure in most studies [5,7,18,19,26,27]. The only exception was observed by Yi Y et al; despite decreases in other parameters (Chao1 index and richness index), they reported an increase in Simpson index, even without statistical significance (p = 0.32) [17].…”

“…Despite its vast benefits, radiation from medical procedures can cause adverse effects [ 8 , 14 , 15 ], including frequent gastrointestinal toxicity during abdominal and pelvic radiotherapy [ 5 , 6 , 7 ]. Current evidence suggests that the gut microbiome influences radiotherapy efficacy [ 16 , 17 ] and radiation-induced gastrointestinal toxicity [ 5 , 7 , 18 , 19 ].…”

“…(Nam et al, 2013) [5] Proteobacteria -Fluctuating pattern-increase after 1 and decreased after the fifth and follow-up (Nam et al, 2013) [5] -Increased (Sahly et al, 2019) [27] -Increased. Tended to return to baseline levels after CRT (El Alam et al, 2021) [19] Class level Gammaproteobacteria -Increased, but returned to normal (El Alam et al, 2021) [19]Bacilli -Increased (El Alam et al, 2021)[19]…”