Microbial Diversity and Composition Is Associated with Patient-Reported Toxicity during Chemoradiation Therapy for Cervical Cancer

Mitra, Analava; Biegert, Greyson; Delgado, Andrea; Karpinets, Tatiana V.; Solley, Travis; Mezzari, Melissa P.; Yoshida-Court, Kyoko; Petrosino, Joe; Mikkelson, Megan D.; Lin, Lilie L.; Eifel, Patricia J.; Zhang, Jianhua; Ramondetta, Lois M.; Jhingran, Anuja; Sims, Travis T.; Schmeler, Kathleen M.; Okhuysen, Pablo C.; Colbert, Lauren E.; Klopp, Ann H.

doi:10.1016/j.ijrobp.2019.12.040

Cited by 51 publications

(73 citation statements)

References 34 publications

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“…The gut microbiota of cervical cancer patients and healthy individuals differ significantly [11], and increasing data suggest that the gut microbiome plays a role in gynecologic cancer including, but not limited to, treatment response and survival [12]. Like patients with gynecologic cancers, patients with other cancers, including anal, rectal, prostate, cervical, and endometrial cancer, are treated primarily with pelvic radiotherapy, with or without chemotherapy, and likely have similar temporal changes in the diversity and composition of the gut microbiome over time as a result of CRT; However, prospective data on the changes the gut microbiome undergoes during pelvic radiotherapy remain scarce, as most studies on the subject have provided only single time-point or retrospective data.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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Section: Interplay Between the Gut Microbiome And Radiotherapy Toxicitymentioning

confidence: 99%

“…Changes in the microbiome are important causative factors in the adverse effects of radiation enteropathy [18,50]. Numerous studies have shown that radiotherapy causes major changes in the gut microbial composition [16][17][18]51]. Several clinical studies of the microbiome before and after radiotherapy for gynecologic or lower gastrointestinal tract cancer all concluded that radiation induced significant changes in the microbiome profile [15][16][17][18]52] including reducing the variation in the gastrointestinal and colonic microbiome.…”

Section: Interplay Between the Gut Microbiome And Radiotherapy Toxicitymentioning

confidence: 99%

“…Numerous studies have shown that radiotherapy causes major changes in the gut microbial composition [16][17][18]51]. Several clinical studies of the microbiome before and after radiotherapy for gynecologic or lower gastrointestinal tract cancer all concluded that radiation induced significant changes in the microbiome profile [15][16][17][18]52] including reducing the variation in the gastrointestinal and colonic microbiome. This reduced variation was notable among patients with gastrointestinal or gynecologic cancer who had diarrhea after irradiation compared with those who did not [16,17].…”

Section: Interplay Between the Gut Microbiome And Radiotherapy Toxicitymentioning

confidence: 99%

“…The gut microbiome can influence both the effectiveness of cancer treatment [10][11][12][13] and the severity of cancer treatment-induced gastrointestinal toxicities [14][15][16][17][18]. Microbiota niche can modify efficacy and toxicity profile of different onco-therapeutic treatment modalities from chemoradiotherapy to immunotherapy.…”

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Radiotherapy and the gut microbiome: facts and fiction

2021

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An ever-growing body of evidence has linked the gut microbiome with both the effectiveness and the toxicity of cancer therapies. Radiotherapy is an effective way to treat tumors, although large variations exist among patients in tumor radio-responsiveness and in the incidence and severity of radiotherapy-induced side effects. Relatively little is known about whether and how the microbiome regulates the response to radiotherapy. Gut microbiota may be an important player in modulating “hot” versus “cold” tumor microenvironment, ultimately affecting treatment efficacy. The interaction of the gut microbiome and radiotherapy is a bidirectional function, in that radiotherapy can disrupt the microbiome and those disruptions can influence the effectiveness of the anticancer treatments. Limited data have shown that interactions between the radiation and the microbiome can have positive effects on oncotherapy. On the other hand, exposure to ionizing radiation leads to changes in the gut microbiome that contribute to radiation enteropathy. The gut microbiome can influence radiation-induced gastrointestinal mucositis through two mechanisms including translocation and dysbiosis. We propose that the gut microbiome can be modified to maximize the response to treatment and minimize adverse effects through the use of personalized probiotics, prebiotics, or fecal microbial transplantation. 16S rRNA sequencing is the most commonly used approach to investigate distribution and diversity of gut microbiome between individuals though it only identifies bacteria level other than strain level. The functional gut microbiome can be studied using methods involving metagenomics, metatranscriptomics, metaproteomics, as well as metabolomics. Multiple ‘-omic’ approaches can be applied simultaneously to the same sample to obtain integrated results. That said, challenges and remaining unknowns in the future that persist at this time include the mechanisms by which the gut microbiome affects radiosensitivity, interactions between the gut microbiome and combination treatments, the role of the gut microbiome with regard to predictive and prognostic biomarkers, the need for multi “-omic” approach for in-depth exploration of functional changes and their effects on host-microbiome interactions, and interactions between gut microbiome, microbial metabolites and immune microenvironment.

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Association between gut microbial change and acute gastrointestinal toxicity in patients with prostate cancer receiving definitive radiation therapy

Jang,

Chung,

Lee

2023

Cancer Medicine

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BackgroundThis prospective study investigated the association between gut microbial changes and acute gastrointestinal toxicities in prostate cancer patients receiving definitive radiation therapy (RT).MethodsSeventy‐nine fecal samples were analyzed. Stool samples were collected at the following timepoints: pre‐RT (prRT), 2 weeks after the start of RT (RT‐2w), 5 weeks after the start of RT (RT‐5w), 1 month after completion of RT (poRT‐1 m), and 3 months after completion of RT (poRT‐3 m). We computed the microbial community polarization index (MCPI) as an indicator of RT‐induced dysbiosis.ResultsPatients experiencing toxicity had lower alpha diversity, especially at RT‐2w (p = 0.037) and RT‐5w (p = 0.003). Compared to patients without toxicity, the MCPI in those experiencing toxicities was significantly elevated (p = 0.019). In terms of predicted metabolic pathways, we found linearly decreasing pathways, including carbon fixation pathways in prokaryotes (p = 0.035) and the bacterial secretion system (p = 0.005), in patients who experienced toxicities.ConclusionsWe showed RT‐induced dysbiosis among patients who experienced toxicities. Reduced diversity and elevated RT‐related MCPI could be helpfully used for developing individualized RT approaches.

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Microbial Diversity and Composition Is Associated with Patient-Reported Toxicity during Chemoradiation Therapy for Cervical Cancer

Cited by 51 publications

References 34 publications

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

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

Radiotherapy and the gut microbiome: facts and fiction

Association between gut microbial change and acute gastrointestinal toxicity in patients with prostate cancer receiving definitive radiation therapy

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