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dc.contributor.authorReis Ferreira, M
dc.contributor.authorAndreyev, HJN
dc.contributor.authorMohammed, K
dc.contributor.authorTruelove, L
dc.contributor.authorGowan, SM
dc.contributor.authorLi, J
dc.contributor.authorGulliford, SL
dc.contributor.authorMarchesi, JR
dc.contributor.authorDearnaley, DP
dc.date.accessioned2019-12-06T15:16:02Z
dc.date.issued2019-11
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2019, 25 (21), pp. 6487 - 6500
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3448
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.ccr-19-0960
dc.description.abstractPurpose Radiotherapy is important in managing pelvic cancers. However, radiation enteropathy may occur and can be dose limiting. The gut microbiota may contribute to the pathogenesis of radiation enteropathy. We hypothesized that the microbiome differs between patients with and without radiation enteropathy. Experimental Design: Three cohorts of patients ( n = 134) were recruited. The early cohort ( n = 32) was followed sequentially up to 12 months post-radiotherapy to assess early radiation enteropathy. Linear mixed models were used to assess microbiota dynamics. The late cohort ( n = 87) was assessed cross-sectionally to assess late radiation enteropathy. The colonoscopy cohort compared the intestinal mucosa microenvironment in patients with radiation enteropathy (cases, n = 9) with healthy controls (controls, n = 6). Fecal samples were obtained from all cohorts. In the colonoscopy cohort, intestinal mucosa samples were taken. Metataxonomics (16S rRNA gene) and imputed metataxonomics (Piphillin) were used to characterize the microbiome. Clinician- and patient-reported outcomes were used for clinical characterization.Results In the acute cohort, we observed a trend for higher preradiotherapy diversity in patients with no self-reported symptoms ( P = 0.09). Dynamically, diversity decreased less over time in patients with rising radiation enteropathy ( P = 0.05). A consistent association between low bacterial diversity and late radiation enteropathy was also observed, albeit nonsignificantly. Higher counts of Clostridium IV, Roseburia , and Phascolarctobacterium significantly associated with radiation enteropathy. Homeostatic intestinal mucosa cytokines related to microbiota regulation and intestinal wall maintenance were significantly reduced in radiation enteropathy [IL7 ( P = 0.05), IL12/IL23p40 ( P = 0.03), IL15 ( P = 0.05), and IL16 ( P = 0.009)]. IL15 inversely correlated with counts of Roseburia and Propionibacterium .Conclusions The microbiota presents opportunities to predict, prevent, or treat radiation enteropathy. We report the largest clinical study to date into associations of the microbiota with acute and late radiation enteropathy. An altered microbiota associates with early and late radiation enteropathy, with clinical implications for risk assessment, prevention, and treatment of radiation-induced side-effects. See related commentary by Lam et al., p. 6280 .
dc.formatPrint-Electronic
dc.format.extent6487 - 6500
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectGastrointestinal Tract
dc.subjectIntestinal Mucosa
dc.subjectFeces
dc.subjectHumans
dc.subjectBacteria
dc.subjectPelvic Neoplasms
dc.subjectRadiation Injuries
dc.subjectRNA, Ribosomal, 16S
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectGastrointestinal Microbiome
dc.subjectRadiation Exposure
dc.titleMicrobiota- and Radiotherapy-Induced Gastrointestinal Side-Effects (MARS) Study: A Large Pilot Study of the Microbiome in Acute and Late-Radiation Enteropathy.
dc.typeJournal Article
dcterms.dateAccepted2019-07-22
rioxxterms.versionofrecord10.1158/1078-0432.ccr-19-0960
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Research
pubs.issue21
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Clinical Academic Radiotherapy (Dearnaley)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Radiotherapy Physics Modelling
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Clinical Academic Radiotherapy (Dearnaley)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Radiotherapy Physics Modelling
pubs.publication-statusPublished
pubs.volume25
pubs.embargo.termsNot known
icr.researchteamClinical Academic Radiotherapy (Dearnaley)en_US
icr.researchteamRadiotherapy Physics Modellingen_US
dc.contributor.icrauthorReis Ferreira, Joseen
dc.contributor.icrauthorDearnaley, Daviden
dc.contributor.icrauthorGulliford, Sarahen


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