Dataset Information

Changes in the Vaginal Microbiome and Associated Toxicities Following Radiation Therapy for Gynecologic Cancers

ABSTRACT: Postmenopausal women often suffer from vaginal symptoms associated with atrophic vaginitis. Additionally, gynecologic cancer survivors may live for decades with additional, clinically significant, persistent vaginal toxicities caused by cancer therapies, including pain, dyspareunia, and sexual dysfunction. The vaginal microbiome (VM) has been previously linked with vaginal symptoms related to menopause (i.e. dryness). Our previous work showed that gynecologic cancer patients exhibit distinct VM profiles from healthy women, with low abundance of lactobacilli and prevalence of multiple opportunistic pathogenic bacteria. Here we explore the association between the dynamics and structure of the vaginal microbiome with the manifestation and persistence of vaginal symptoms, during one year after completion of cancer therapies, while controlling for clinical and sociodemographic factors. We compared cross-sectionally the vaginal microbiome in 134 women, 64 gynecologic patients treated with radiotherapy and 68 healthy controls, and we longitudinally followed a subset of 52 women quarterly (4 times in a year: pre-radiation therapy, 2, 6 and 12 months post-therapy). Differences among the VM profiles of cancer and healthy women were more pronounced with the progression of time. Cancer patients had higher diversity VMs and a variety of vaginal community types (CTs) that are not dominated by Lactobacilli, with extensive VM variation between individuals. Additionally, cancer patients exhibit highly unstable VMs (based on Bray-Curtis distances) compared to healthy controls. Vaginal symptoms prevalent in cancer patients included vaginal pain (40%), hemorrhage (35%), vaginismus (28%) and inflammation (20%), while symptoms such as dryness (45%), lack of lubrication (33%) and dyspareunia (32%) were equally or more prominent in healthy women at baseline. However, 24% of cancer patients experienced persistent symptoms at all time points, as opposed to 12% of healthy women. Symptom persistence was strongly inversely correlated with VM stability; for example, patients with persistent dryness or abnormally high pH have the most unstable microbiomes. Associations were identified between vaginal symptoms and individual bacterial taxa, including: Prevotella with vaginal dryness, Delftia with pain following vaginal intercourse, and Gemillaceaea with low levels of lubrication during intercourse. Taken together our results indicate that gynecologic cancer therapy is associated with reduced vaginal microbiome stability and vaginal symptom persistence.

SUBMITTER: Tsementzi D

PROVIDER: S-EPMC8580013 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundComposition and maintenance of the microbiome is vital to gut homeostasis. However, there is limited knowledge regarding the impact of high doses of radiation, which can occur as a result of cancer radiation therapy, nuclear accidents or intentional release of a nuclear or radioactive weapon, on the composition of the gut microbiome. Therefore, we sought to analyze alterations to the gut microbiome of nonhuman primates (NHPs) exposed to high doses of radiation. Fecal samples were collected from 19 NHPs (Chinese rhesus macaques, Macaca mulatta) 1 day prior and 1 and 4 days after exposure to 7.4 Gy cobalt-60 gamma-radiation (LD70-80/60). The 16S V4 rRNA sequences were extracted from each sample, followed by bioinformatics analysis using the QIIME platform.ResultsAlpha Diversity (Shannon Diversity Index), revealed no major difference between pre- and post-irradiation, whereas Beta diversity analysis showed significant differences in the microbiome after irradiation (day + 4) compared to baseline (pre-irradiation). The Firmicutes/Bacteriodetes ratio, a factor known to be associated with disruption of metabolic homeostasis, decreased from 1.2 to less than 1 post-radiation exposure. Actinobacillus, Bacteroides, Prevotella (Paraprevotellaceae family) and Veillonella genera were significantly increased by more than 2-fold and Acinetobacter and Aerococcus genus were decreased by more than 10-fold post-irradiation. Fifty-two percent (10/19) of animals exposed to radiation demonstrated diarrhea at day 4 post-irradiation. Comparison of microbiome composition of feces from animals with and without diarrhea at day 4 post-irradiation revealed an increase in Lactobacillus reuteri associated with diarrhea and a decrease of Lentisphaerae and Verrucomicrobioa phyla and Bacteroides in animals exhibiting diarrhea. Animals with diarrhea at day 4 post-irradiation, had significantly lower levels of Lentisphaere and Verrucomicrobia phyla and Bacteroides genus at baseline before irradiation, suggesting a potential association between the prevalence of microbiomes and differential susceptibility to radiation-induced diarrhea.ConclusionsOur findings demonstrate that substantial alterations in the microbiome composition of NHPs occur following radiation injury and provide insight into early changes with high-dose, whole-body radiation exposure. Future studies will help identify microbiome biomarkers of radiation exposure and develop effective therapeutic intervention to mitigate the radiation injury.

Project description: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. 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.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 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.

Dataset Information

Changes in the Vaginal Microbiome and Associated Toxicities Following Radiation Therapy for Gynecologic Cancers

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets