{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:38:03Z","timestamp":1791488283530,"version":"4.3.4"},"reference-count":118,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T00:00:00Z","timestamp":1610496000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T00:00:00Z","timestamp":1610496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871895"],"award-info":[{"award-number":["81871895"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Young Taishan Scholars and Academic Promotion Program of Shandong First Medical University","award":["2019RC003"],"award-info":[{"award-number":["2019RC003"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Radiat Oncol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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 \u201chot\u201d versus \u201ccold\u201d 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 \u2018-omic\u2019 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 \u201c-omic\u201d 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.<\/jats:p>","DOI":"10.1186\/s13014-020-01735-9","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T20:02:42Z","timestamp":1610481762000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":179,"title":["Radiotherapy and the gut microbiome: facts and fiction"],"prefix":"10.1186","volume":"16","author":[{"given":"Jing","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinbo","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,13]]},"reference":[{"key":"1735_CR1","doi-asserted-by":"publisher","first-page":"e7765","DOI":"10.1136\/bmj.e7765","volume":"345","author":"SS Ahmad","year":"2012","unstructured":"Ahmad SS, Duke S, Jena R, Williams MV, Burnet NG. Advances in radiotherapy. BMJ. 2012;345:e7765. https:\/\/doi.org\/10.1136\/bmj.e7765.","journal-title":"BMJ"},{"issue":"12","key":"1735_CR2","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1038\/nrclinonc.2012.194","volume":"9","author":"DA Jaffray","year":"2012","unstructured":"Jaffray DA. Image-guided radiotherapy: from current concept to future perspectives. Nat Rev Clin Oncol. 2012;9(12):688\u201399. https:\/\/doi.org\/10.1038\/nrclinonc.2012.194.","journal-title":"Nat Rev Clin Oncol"},{"issue":"6","key":"1735_CR3","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1002\/cncr.21324","volume":"104","author":"G Delaney","year":"2005","unstructured":"Delaney G, Jacob S, Featherstone C, Barton M. The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence-based clinical guidelines. Cancer. 2005;104(6):1129\u201337. https:\/\/doi.org\/10.1002\/cncr.21324.","journal-title":"Cancer"},{"issue":"2","key":"1735_CR4","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1038\/nrc2587","volume":"9","author":"GC Barnett","year":"2009","unstructured":"Barnett GC, West CM, Dunning AM, Elliott RM, Coles CE, Pharoah PDP, et al. Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype. Nat Rev Cancer. 2009;9(2):134\u201342. https:\/\/doi.org\/10.1038\/nrc2587.","journal-title":"Nat Rev Cancer"},{"issue":"4","key":"1735_CR5","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/nrc3007","volume":"11","author":"AC Begg","year":"2011","unstructured":"Begg AC, Stewart FA, Vens C. Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer. 2011;11(4):239\u201353. https:\/\/doi.org\/10.1038\/nrc3007.","journal-title":"Nat Rev Cancer"},{"issue":"1","key":"1735_CR6","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1186\/s13046-019-1405-7","volume":"38","author":"SY Park","year":"2019","unstructured":"Park SY, Lee CJ, Choi JH, Kim JH, Kim JW, Kim JY, et al. The JAK2\/STAT3\/CCND2 axis promotes colorectal cancer stem cell persistence and radioresistance. J Exp Clin Cancer Res. 2019;38(1):399. https:\/\/doi.org\/10.1186\/s13046-019-1405-7.","journal-title":"J Exp Clin Cancer Res"},{"issue":"5","key":"1735_CR7","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/s41575-019-0247-2","volume":"17","author":"AM Buckley","year":"2020","unstructured":"Buckley AM, Lynam-Lennon N, O\u2019Neill H, O\u2019Sullivan J. Targeting hallmarks of cancer to enhance radiosensitivity in gastrointestinal cancers. Nat Rev Gastroenterol Hepatol. 2020;17(5):298\u2013313. https:\/\/doi.org\/10.1038\/s41575-019-0247-2.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"2","key":"1735_CR8","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1053\/SRAO00400068","volume":"4","author":"SM Bentzen","year":"1994","unstructured":"Bentzen SM, Overgaard J. Patient-to-patient variability in the expression of radiation-induced normal tissue injury. Semin Radiat Oncol. 1994;4(2):68\u201380. https:\/\/doi.org\/10.1053\/SRAO00400068.","journal-title":"Semin Radiat Oncol"},{"issue":"3","key":"1735_CR9","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.radonc.2009.06.015","volume":"92","author":"CN Andreassen","year":"2009","unstructured":"Andreassen CN, Alsner J. Genetic variants and normal tissue toxicity after radiotherapy: a systematic review. Radiother Oncol. 2009;92(3):299\u2013309. https:\/\/doi.org\/10.1016\/j.radonc.2009.06.015.","journal-title":"Radiother Oncol"},{"issue":"6161","key":"1735_CR10","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1126\/science.1240537","volume":"342","author":"S Viaud","year":"2013","unstructured":"Viaud S, Saccheri F, Mignot G, Yamazaki T, Daill\u00e8re R, Hannani D, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science. 2013;342(6161):971\u20136. https:\/\/doi.org\/10.1126\/science.1240537.","journal-title":"Science"},{"issue":"6161","key":"1735_CR11","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1126\/science.1240527","volume":"342","author":"N Iida","year":"2013","unstructured":"Iida N, Dzutsev A, Stewart CA, Smith L, Bouladoux N, Weingarten RA, et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science. 2013;342(6161):967\u201370. https:\/\/doi.org\/10.1126\/science.1240527.","journal-title":"Science"},{"issue":"6264","key":"1735_CR12","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1126\/science.aad1329","volume":"350","author":"M V\u00e9tizou","year":"2015","unstructured":"V\u00e9tizou M, Pitt JM, Daill\u00e8re R, Lepage P, Waldschmitt N, Flament C, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350(6264):1079\u201384. https:\/\/doi.org\/10.1126\/science.aad1329.","journal-title":"Science"},{"issue":"6264","key":"1735_CR13","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1126\/science.aac4255","volume":"350","author":"A Sivan","year":"2015","unstructured":"Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350(6264):1084\u20139. https:\/\/doi.org\/10.1126\/science.aac4255.","journal-title":"Science"},{"issue":"4","key":"1735_CR14","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.4049\/jimmunol.1402481","volume":"194","author":"M Frank","year":"2015","unstructured":"Frank M, Hennenberg EM, Eyking A, R\u00fcnzi M, Gerken G, Scott P, et al. TLR signaling modulates side effects of anticancer therapy in the small intestine. J Immunol. 2015;194(4):1983\u201395. https:\/\/doi.org\/10.4049\/jimmunol.1402481.","journal-title":"J Immunol"},{"issue":"7","key":"1735_CR15","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1111\/j.1572-0241.2008.01868.x","volume":"103","author":"C Manichanh","year":"2008","unstructured":"Manichanh C, Varela E, Martinez C, Antolin M, Llopis M, Dor\u00e9 J, et al. The gut microbiota predispose to the pathophysiology of acute postradiotherapy diarrhea. Am J Gastroenterol. 2008;103(7):1754\u201361. https:\/\/doi.org\/10.1111\/j.1572-0241.2008.01868.x.","journal-title":"Am J Gastroenterol"},{"issue":"12","key":"1735_CR16","doi-asserted-by":"publisher","first-page":"e82659","DOI":"10.1371\/journal.pone.0082659","volume":"8","author":"YD Nam","year":"2013","unstructured":"Nam YD, Kim HJ, Seo JG, Kang SW, Bae JW. Impact of pelvic radiotherapy on gut microbiota of gynecological cancer patients revealed by massive pyrosequencing. PLoS ONE. 2013;8(12):e82659. https:\/\/doi.org\/10.1371\/journal.pone.0082659.","journal-title":"PLoS ONE"},{"issue":"5","key":"1735_CR17","doi-asserted-by":"publisher","first-page":"e0126312","DOI":"10.1371\/journal.pone.0126312","volume":"10","author":"A Wang","year":"2015","unstructured":"Wang A, Ling Z, Yang Z, Kiela PR, Wang T, Wang C, et al. Gut microbial dysbiosis may predict diarrhea and fatigue in patients undergoing pelvic cancer radiotherapy: a pilot study. PLoS ONE. 2015;10(5):e0126312. https:\/\/doi.org\/10.1371\/journal.pone.0126312.","journal-title":"PLoS ONE"},{"issue":"1","key":"1735_CR18","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.ijrobp.2019.12.040","volume":"107","author":"A Mitra","year":"2020","unstructured":"Mitra A, Grossman Biegert GW, Delgado AY, Karpinets TV, Solley TN, Mezzari MP, et al. Microbial diversity and composition is associated with patient-reported toxicity during chemoradiation therapy for cervical cancer. Int J Radiat Oncol Biol Phys. 2020;107(1):163\u201371. https:\/\/doi.org\/10.1016\/j.ijrobp.2019.12.040.","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"3","key":"1735_CR19","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1007\/s11888-019-00435-1","volume":"15","author":"A Saeed","year":"2019","unstructured":"Saeed A, Eshrat FF, Umar S, Saeed A. The duplex interaction of microbiome with chemoradiation and immunotherapy: potential implications for colorectal cancer. Curr Colorectal Cancer Rep. 2019;15(3):98\u2013104. https:\/\/doi.org\/10.1007\/s11888-019-00435-1.","journal-title":"Curr Colorectal Cancer Rep"},{"issue":"6","key":"1735_CR20","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1038\/nrgastro.2017.20","volume":"14","author":"JL Alexander","year":"2017","unstructured":"Alexander JL, Wilson ID, Teare J, Marchesi JR, Nicholson JK, Kinross JM. Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat Rev Gastroenterol Hepatol. 2017;14(6):356\u201365. https:\/\/doi.org\/10.1038\/nrgastro.2017.20.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"5","key":"1735_CR21","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1038\/nrc.2017.13","volume":"17","author":"S Roy","year":"2017","unstructured":"Roy S, Trinchieri G. Microbiota: a key orchestrator of cancer therapy. Nat Rev Cancer. 2017;17(5):271\u201385. https:\/\/doi.org\/10.1038\/nrc.2017.13.","journal-title":"Nat Rev Cancer"},{"key":"1735_CR22","doi-asserted-by":"publisher","first-page":"24","DOI":"10.3389\/fmolb.2014.00024","volume":"1","author":"R Baskar","year":"2014","unstructured":"Baskar R, Dai J, Wenlong N, Yeo R, Yeoh KW. Biological response of cancer cells to radiation treatment. Front Mol Biosci. 2014;1:24. https:\/\/doi.org\/10.3389\/fmolb.2014.00024.","journal-title":"Front Mol Biosci"},{"issue":"10","key":"1735_CR23","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1002\/stem.3051","volume":"37","author":"I Kareva","year":"2019","unstructured":"Kareva I. Metabolism and gut microbiota in cancer immunoediting, CD8\/Treg Ratios, immune cell homeostasis, and cancer (immuno)therapy: concise review. Stem Cells. 2019;37(10):1273\u201380. https:\/\/doi.org\/10.1002\/stem.3051.","journal-title":"Stem Cells"},{"issue":"3","key":"1735_CR24","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/s41591-019-0377-7","volume":"25","author":"BA Helmink","year":"2019","unstructured":"Helmink BA, Khan MAW, Hermann A, Gopalakrishnan V, Wargo JA. The microbiome, cancer, and cancer therapy. Nat Med. 2019;25(3):377\u201388. https:\/\/doi.org\/10.1038\/s41591-019-0377-7.","journal-title":"Nat Med"},{"key":"1735_CR25","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/bs.pmbts.2020.04.004","volume":"171","author":"SL Chan","year":"2020","unstructured":"Chan SL. Microbiome and cancer treatment: are we ready to apply in clinics? Prog Mol Biol Transl Sci. 2020;171:301\u20138. https:\/\/doi.org\/10.1016\/bs.pmbts.2020.04.004.","journal-title":"Prog Mol Biol Transl Sci"},{"key":"1735_CR26","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/978-3-030-16391-4_10","volume":"178","author":"S Gately","year":"2019","unstructured":"Gately S. Human microbiota and personalized cancer treatments: role of commensal microbes in treatment outcomes for cancer patients. Cancer Treat Res. 2019;178:253\u201364. https:\/\/doi.org\/10.1007\/978-3-030-16391-4_10.","journal-title":"Cancer Treat Res"},{"key":"1735_CR27","doi-asserted-by":"publisher","first-page":"116680","DOI":"10.1016\/j.lfs.2019.116680","volume":"233","author":"Y Hekmatshoar","year":"2019","unstructured":"Hekmatshoar Y, Rahbar Saadat Y, Hosseiniyan Khatibi SM, Ozkan T, Zununi Vahed F, Nariman-Saleh-Fam Z, et al. The impact of tumor and gut microbiotas on cancer therapy: beneficial or detrimental? Life Sci. 2019;233:116680. https:\/\/doi.org\/10.1016\/j.lfs.2019.116680.","journal-title":"Life Sci"},{"issue":"10","key":"1735_CR28","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1007\/s11934-019-0922-4","volume":"20","author":"KM Wheeler","year":"2019","unstructured":"Wheeler KM, Liss MA. The microbiome and prostate cancer risk. Curr Urol Rep. 2019;20(10):66. https:\/\/doi.org\/10.1007\/s11934-019-0922-4.","journal-title":"Curr Urol Rep"},{"key":"1735_CR29","doi-asserted-by":"publisher","first-page":"869","DOI":"10.3332\/ecancer.2018.869","volume":"12","author":"AJ Scott","year":"2018","unstructured":"Scott AJ, Merrifield CA, Younes JA, Pekelharing EP. Pre-, pro- and synbiotics in cancer prevention and treatment\u2014a review of basic and clinical research. Ecancermedicalscience. 2018;12:869. https:\/\/doi.org\/10.3332\/ecancer.2018.869.","journal-title":"Ecancermedicalscience"},{"key":"1735_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.anaerobe.2015.01.004","volume":"33","author":"YS Kim","year":"2015","unstructured":"Kim YS, Kim J, Park SJ. High-throughput 16S rRNA gene sequencing reveals alterations of mouse intestinal microbiota after radiotherapy. Anaerobe. 2015;33:1\u20137. https:\/\/doi.org\/10.1016\/j.anaerobe.2015.01.004.","journal-title":"Anaerobe"},{"issue":"4","key":"1735_CR31","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/j.ijrobp.2020.04.015","volume":"107","author":"BS Jang","year":"2020","unstructured":"Jang BS, Chang JH, Chie EK, Kim K, Park JW, Kim MJ, et al. Gut Microbiome composition is associated with a pathologic response after preoperative chemoradiation in patients with rectal cancer. Int J Radiat Oncol Biol Phys. 2020;107(4):736\u201346. https:\/\/doi.org\/10.1016\/j.ijrobp.2020.04.015.","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"5","key":"1735_CR32","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1111\/apt.12878","volume":"40","author":"Y Touchefeu","year":"2014","unstructured":"Touchefeu Y, Montassier E, Nieman K, Gastinne T, Potel G, Bruley des Varannes S, et al. Systematic review: the role of the gut microbiota in chemotherapy- or radiation-induced gastrointestinal mucositis: current evidence and potential clinical applications. Aliment Pharmacol Ther. 2014;40(5):409\u201321. https:\/\/doi.org\/10.1111\/apt.12878.","journal-title":"Aliment Pharmacol Ther."},{"issue":"4","key":"1735_CR33","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/j.cell.2019.07.008","volume":"178","author":"E Riquelme","year":"2019","unstructured":"Riquelme E, Zhang Y, Zhang L, Montiel M, Zoltan M, Dong W, et al. Tumor microbiome diversity and composition influence pancreatic cancer outcomes. Cell. 2019;178(4):795-806.e12. https:\/\/doi.org\/10.1016\/j.cell.2019.07.008.","journal-title":"Cell"},{"issue":"1","key":"1735_CR34","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1172\/JCI124332","volume":"130","author":"M Uribe-Herranz","year":"2020","unstructured":"Uribe-Herranz M, Rafail S, Beghi S, Gil-de-G\u00f3mez L, Verginadis I, Bittinger K, et al. Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response. J Clin Invest. 2020;130(1):466\u201379. https:\/\/doi.org\/10.1172\/JCI124332.","journal-title":"J Clin Invest"},{"issue":"4","key":"1735_CR35","doi-asserted-by":"publisher","first-page":"448","DOI":"10.15252\/emmm.201606932","volume":"9","author":"M Cui","year":"2017","unstructured":"Cui M, Xiao H, Li Y, Zhou L, Zhao S, Luo D, et al. Faecal microbiota transplantation protects against radiation-induced toxicity. EMBO Mol Med. 2017;9(4):448\u201361. https:\/\/doi.org\/10.15252\/emmm.201606932.","journal-title":"EMBO Mol Med"},{"issue":"11","key":"1735_CR36","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.3390\/ijms17111786","volume":"17","author":"M Cui","year":"2016","unstructured":"Cui M, Xiao H, Luo D, Zhang X, Zhao S, Zheng Q, et al. Circadian rhythm shapes the gut microbiota affecting host radiosensitivity. Int J Mol Sci. 2016;17(11):1786. https:\/\/doi.org\/10.3390\/ijms17111786.","journal-title":"Int J Mol Sci"},{"issue":"4","key":"1735_CR37","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.clon.2016.12.005","volume":"29","author":"S Chan","year":"2017","unstructured":"Chan S, Rowbottom L, McDonald R, Bjarnason GA, Tsao M, Danjoux C, et al. Does the time of radiotherapy affect treatment outcomes? A review of the literature. Clin Oncol (R Coll Radiol). 2017;29(4):231\u20138. https:\/\/doi.org\/10.1016\/j.clon.2016.12.005.","journal-title":"Clin Oncol (R Coll Radiol)"},{"issue":"6","key":"1735_CR38","doi-asserted-by":"publisher","first-page":"e177","DOI":"10.1038\/cddis.2011.56","volume":"2","author":"Y Kuwahara","year":"2011","unstructured":"Kuwahara Y, Oikawa T, Ochiai Y, Roudkenar MH, Fukumoto M, Shimura T, et al. Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy. Cell Death Dis. 2011;2(6):e177. https:\/\/doi.org\/10.1038\/cddis.2011.56.","journal-title":"Cell Death Dis"},{"issue":"10","key":"1735_CR39","doi-asserted-by":"publisher","first-page":"3152","DOI":"10.1158\/1078-0432.CCR-18-2951","volume":"25","author":"D Digomann","year":"2019","unstructured":"Digomann D, Kurth I, Tyutyunnykova A, Chen O, L\u00f6ck S, Gorodetska I, et al. The CD98 heavy chain is a marker and regulator of head and neck squamous cell carcinoma radiosensitivity. Clin Cancer Res. 2019;25(10):3152\u201363. https:\/\/doi.org\/10.1158\/1078-0432.CCR-18-2951.","journal-title":"Clin Cancer Res"},{"issue":"10","key":"1735_CR40","doi-asserted-by":"publisher","first-page":"1850","DOI":"10.1080\/15548627.2019.1639302","volume":"15","author":"D Digomann","year":"2019","unstructured":"Digomann D, Linge A, Dubrovska A. SLC3A2\/CD98hc, autophagy and tumor radioresistance: a link confirmed. Autophagy. 2019;15(10):1850\u20131. https:\/\/doi.org\/10.1080\/15548627.2019.1639302.","journal-title":"Autophagy"},{"issue":"3","key":"1735_CR41","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.cell.2017.07.008","volume":"170","author":"T Yu","year":"2017","unstructured":"Yu T, Guo F, Yu Y, Sun T, Ma D, Han J, et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell. 2017;170(3):548-63.e16. https:\/\/doi.org\/10.1016\/j.cell.2017.07.008.","journal-title":"Cell"},{"issue":"5","key":"1735_CR42","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1038\/nrc1877","volume":"6","author":"R Kalluri","year":"2006","unstructured":"Kalluri R, Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer. 2006;6(5):392\u2013401. https:\/\/doi.org\/10.1038\/nrc1877.","journal-title":"Nat Rev Cancer"},{"issue":"37","key":"1735_CR43","doi-asserted-by":"publisher","first-page":"132254","DOI":"10.1073\/pnas.0504830102","volume":"102","author":"PA Crawford","year":"2005","unstructured":"Crawford PA, Gordon JI. Microbial regulation of intestinal radiosensitivity. Proc Natl Acad Sci USA. 2005;102(37):132254\u20139. https:\/\/doi.org\/10.1073\/pnas.0504830102.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"7","key":"1735_CR44","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1111\/j.1462-2920.2011.02482.x","volume":"13","author":"C Grootaert","year":"2011","unstructured":"Grootaert C, Van de Wiele T, Van Roosbroeck I, Possemiers S, Vercoutter-Edouart AS, Verstraete W, et al. Bacterial monocultures, propionate, butyrate and H2O2 modulate the expression, secretion and structure of the fasting-induced adipose factor in gut epithelial cell lines. Environ Microbiol. 2011;13(7):1778\u201389. https:\/\/doi.org\/10.1111\/j.1462-2920.2011.02482.x.","journal-title":"Environ Microbiol"},{"issue":"11","key":"1735_CR45","doi-asserted-by":"publisher","first-page":"G1025","DOI":"10.1152\/ajpgi.00293.2012","volume":"304","author":"A Korecka","year":"2013","unstructured":"Korecka A, de Wouters T, Cultrone A, Lapaque N, Pettersson S, Dor\u00e9 J, et al. ANGPTL4 expression induced by butyrate and rosiglitazone in human intestinal epithelial cells utilizes independent pathways. Am J Physiol Gastrointest Liver Physiol. 2013;304(11):G1025\u201337. https:\/\/doi.org\/10.1152\/ajpgi.00293.2012.","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"5","key":"1735_CR46","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1016\/j.clnu.2013.10.015","volume":"33","author":"M Demers","year":"2014","unstructured":"Demers M, Dagnault A, Desjardins J. A randomized double-blind controlled trial: impact of probiotics on diarrhea in patients treated with pelvic radiation. Clin Nutr. 2014;33(5):761\u20137. https:\/\/doi.org\/10.1016\/j.clnu.2013.10.015.","journal-title":"Clin Nutr"},{"issue":"9 Suppl","key":"1735_CR47","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.1002\/cncr.20162","volume":"100","author":"ST Sonis","year":"2004","unstructured":"Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004;100(9 Suppl):1995\u20132025. https:\/\/doi.org\/10.1002\/cncr.20162.","journal-title":"Cancer"},{"issue":"1","key":"1735_CR48","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.cden.2007.10.002","volume":"52","author":"RV Lalla","year":"2008","unstructured":"Lalla RV, Sonis ST, Peterson DE. Management of oral mucositis in patients who have cancer. Dent Clin North Am. 2008;52(1):61\u201377. https:\/\/doi.org\/10.1016\/j.cden.2007.10.002.","journal-title":"Dent Clin North Am."},{"issue":"5","key":"1735_CR49","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1080\/17474124.2019.1595586","volume":"13","author":"G Al-Qadami","year":"2019","unstructured":"Al-Qadami G, Van Sebille Y, Le H, Bowen J. Gut microbiota: implications for radiotherapy response and radiotherapy-induced mucositis. Expert Rev Gastroenterol Hepatol. 2019;13(5):485\u201396. https:\/\/doi.org\/10.1080\/17474124.2019.1595586.","journal-title":"Expert Rev Gastroenterol Hepatol"},{"issue":"3","key":"1735_CR50","doi-asserted-by":"publisher","first-page":"e139","DOI":"10.1016\/S1470-2045(13)70504-7","volume":"15","author":"MR Ferreira","year":"2014","unstructured":"Ferreira MR, Muls A, Dearnaley DP, Andreyev HJ. Microbiota and radiation-induced bowel toxicity: lessons from inflammatory bowel disease for the radiation oncologist. Lancet Oncol. 2014;15(3):e139\u201347. https:\/\/doi.org\/10.1016\/S1470-2045(13)70504-7.","journal-title":"Lancet Oncol"},{"issue":"1","key":"1735_CR51","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1136\/gutjnl-2017-313789","volume":"67","author":"S Gerassy-Vainberg","year":"2018","unstructured":"Gerassy-Vainberg S, Blatt A, Danin-Poleg Y, Gershovich K, Sabo E, Nevelsky A, et al. Radiation induces proinflammatory dysbiosis: transmission of inflammatory susceptibility by host cytokine induction. Gut. 2018;67(1):97\u2013107. https:\/\/doi.org\/10.1136\/gutjnl-2017-313789.","journal-title":"Gut"},{"issue":"3","key":"1735_CR52","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1667\/RR14306.1","volume":"186","author":"M Goudarzi","year":"2016","unstructured":"Goudarzi M, Mak TD, Jacobs JP, Moon BH, Strawn SJ, Braun J, et al. An integrated multi-omic approach to assess radiation injury on the host-microbiome axis. Radiat Res. 2016;186(3):219\u201334. https:\/\/doi.org\/10.1667\/RR14306.1.","journal-title":"Radiat Res"},{"issue":"3","key":"1735_CR53","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1007\/s00248-013-0355-4","volume":"67","author":"E Montassier","year":"2014","unstructured":"Montassier E, Batard E, Massart S, Gastinne T, Carton T, Caillon J, et al. 16S rRNA gene pyrosequencing reveals shift in patient faecal microbiota during high-dose chemotherapy as conditioning regimen for bone marrow transplantation. Microb Ecol. 2014;67(3):690\u20139. https:\/\/doi.org\/10.1007\/s00248-013-0355-4.","journal-title":"Microb Ecol"},{"issue":"1","key":"1735_CR54","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1200\/JOP.2016.018614","volume":"13","author":"K Neemann","year":"2017","unstructured":"Neemann K, Freifeld A. Clostridium difficile-associated diarrhea in the oncology patient. J Oncol Pract. 2017;13(1):25\u201330. https:\/\/doi.org\/10.1200\/JOP.2016.018614.","journal-title":"J Oncol Pract"},{"issue":"5","key":"1735_CR55","doi-asserted-by":"publisher","first-page":"e1000879","DOI":"10.1371\/journal.ppat.1000879","volume":"6","author":"MJ van Vliet","year":"2010","unstructured":"van Vliet MJ, Harmsen HJ, de Bont ES, Tissing WJ. The role of intestinal microbiota in the development and severity of chemotherapy-induced mucositis. PLoS Pathog. 2010;6(5):e1000879. https:\/\/doi.org\/10.1371\/journal.ppat.1000879.","journal-title":"PLoS Pathog"},{"issue":"6","key":"1735_CR56","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1158\/1535-7163.MCT-15-0990","volume":"15","author":"HR Wardill","year":"2016","unstructured":"Wardill HR, Gibson RJ, Van Sebille YZA, Secombe KR, Coller JK, White IA, et al. Irinotecan-induced gastrointestinal dysfunction and pain are mediated by common TLR4-dependent mechanisms. Mol Cancer Ther. 2016;15(6):1376\u201386. https:\/\/doi.org\/10.1158\/1535-7163.MCT-15-0990.","journal-title":"Mol Cancer Ther"},{"issue":"6","key":"1735_CR57","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1016\/s0016-5085(00)70363-5","volume":"118","author":"T Riehl","year":"2000","unstructured":"Riehl T, Cohn S, Tessner T, Schloemann S, Stenson WF. Lipopolysaccharide is radioprotective in the mouse intestine through a prostaglandin-mediated mechanism. Gastroenterology. 2000;118(6):1106\u201316. https:\/\/doi.org\/10.1016\/s0016-5085(00)70363-5.","journal-title":"Gastroenterology"},{"issue":"1","key":"1735_CR58","doi-asserted-by":"publisher","first-page":"G166","DOI":"10.1152\/ajpgi.00537.2002","volume":"286","author":"TE Riehl","year":"2004","unstructured":"Riehl TE, Newberry RD, Lorenz RG, Stenson WF. TNFR1 mediates the radioprotective effects of lipopolysaccharide in the mouse intestine. Am J Physiol Gastrointest Liver Physiol. 2004;286(1):G166\u201373. https:\/\/doi.org\/10.1152\/ajpgi.00537.2002.","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"8","key":"1735_CR59","doi-asserted-by":"publisher","first-page":"2452","DOI":"10.1073\/pnas.0306734101","volume":"101","author":"LJ Egan","year":"2004","unstructured":"Egan LJ, Eckmann L, Greten FR, Chae S, Li ZW, Myhre GM, et al. I\u03baB-kinase\u03b2-dependent NF-\u03baB activation provides radioprotection to the intestinal epithelium. Proc Natl Acad Sci USA. 2004;101(8):2452\u20137. https:\/\/doi.org\/10.1073\/pnas.0306734101.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1735_CR60","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.critrevonc.2019.09.003","volume":"143","author":"S Gori","year":"2019","unstructured":"Gori S, Inno A, Belluomini L, Bocus P, Bisoffi Z, Russo A, Arcaro G. Gut microbiota and cancer: how gut microbiota modulates activity, efficacy and toxicity of antitumoral therapy. Crit Rev Oncol Hematol. 2019;143:139\u201347. https:\/\/doi.org\/10.1016\/j.critrevonc.2019.09.003.","journal-title":"Crit Rev Oncol Hematol"},{"issue":"12","key":"1735_CR61","doi-asserted-by":"publisher","first-page":"7577","DOI":"10.1007\/s13197-015-1921-1","volume":"52","author":"KR Pandey","year":"2015","unstructured":"Pandey KR, Naik SR, Vakil BV. Probiotics, prebiotics and synbiotics\u2014a review. J Food Sci Technol. 2015;52(12):7577\u201387. https:\/\/doi.org\/10.1007\/s13197-015-1921-1.","journal-title":"J Food Sci Technol"},{"key":"1735_CR62","doi-asserted-by":"publisher","first-page":"942","DOI":"10.3389\/fimmu.2017.00942","volume":"8","author":"M Zhang","year":"2017","unstructured":"Zhang M, Sun K, Wu Y, Yang Y, Tso P, Wu Z. Interactions between intestinal microbiota and host immune response in inflammatory bowel disease. Front Immunol. 2017;8:942. https:\/\/doi.org\/10.3389\/fimmu.2017.00942.","journal-title":"Front Immunol"},{"issue":"6","key":"1735_CR63","doi-asserted-by":"publisher","first-page":"7161","DOI":"10.18632\/oncotarget.6881","volume":"7","author":"FJ Cousin","year":"2016","unstructured":"Cousin FJ, Jouan-Lanhouet S, Th\u00e9ret N, Brenner C, Jouan E, Le Moigne-Muller G, et al. The probiotic Propionibacterium freudenreichii as a new adjuvant for TRAIL-based therapy in colorectal cancer. Oncotarget. 2016;7(6):7161\u201378. https:\/\/doi.org\/10.18632\/oncotarget.6881.","journal-title":"Oncotarget"},{"issue":"9","key":"1735_CR64","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1007\/s00535-015-1158-9","volume":"51","author":"M Lenoir","year":"2016","unstructured":"Lenoir M, Del Carmen S, Cortes-Perez NG, Lozano-Ojalvo D, Mu\u00f1oz-Provencio D, Chain F, et al. Lactobacillus casei BL23 regulates Treg and Th17 T-cell populations and reduces DMH-associated colorectal cancer. J Gastroenterol. 2016;51(9):862\u201373. https:\/\/doi.org\/10.1007\/s00535-015-1158-9.","journal-title":"J Gastroenterol"},{"key":"1735_CR65","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.intimp.2016.11.017","volume":"42","author":"S Del Carmen","year":"2017","unstructured":"Del Carmen S, de Moreno de LeBlanc A, Levit R, Levit R, Azevedo V, Langella P, et al. Anti-cancer effect of lactic acid bacteria expressing antioxidant enzymes or IL-10 in a colorectal cancer mouse model. Int Immunopharmacol. 2017;42:122\u20139. https:\/\/doi.org\/10.1016\/j.intimp.2016.11.017.","journal-title":"Int Immunopharmacol."},{"issue":"4","key":"1735_CR66","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1089\/rej.2013.1537","volume":"17","author":"D Mohania","year":"2014","unstructured":"Mohania D, Kansal VK, Kruzliak P, Kumari A. Probiotic Dahi containing Lactobacillus acidophilus and Bifidobacterium bifidum modulates the formation of aberrant crypt foci, mucin-depleted foci, and cell proliferation on 1,2-dimethylhydrazine-induced colorectal carcinogenesis in Wistar rats. Rejuvenation Res. 2014;17(4):325\u201333. https:\/\/doi.org\/10.1089\/rej.2013.1537.","journal-title":"Rejuvenation Res"},{"issue":"1","key":"1735_CR67","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41551-017-0181-y","volume":"2","author":"CL Ho","year":"2018","unstructured":"Ho CL, Tan HQ, Chua KJ, Kang A, Lim KH, Ling KL, et al. Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention. Nat Biomed Eng. 2018;2(1):27\u201337. https:\/\/doi.org\/10.1038\/s41551-017-0181-y.","journal-title":"Nat Biomed Eng"},{"issue":"6","key":"1735_CR68","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.jamcollsurg.2019.09.002","volume":"229","author":"J Franko","year":"2019","unstructured":"Franko J, Raman S, Krishnan N, Frankova D, Tee MC, Brahmbhatt R, et al. Randomized trial of perioperative probiotics among patients undergoing major abdominal operation. J Am Coll Surg. 2019;229(6):533-40.e1. https:\/\/doi.org\/10.1016\/j.jamcollsurg.2019.09.002.","journal-title":"J Am Coll Surg"},{"issue":"6","key":"1735_CR69","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1097\/SLA.0000000000003581","volume":"271","author":"AH Chowdhury","year":"2020","unstructured":"Chowdhury AH, Adiamah A, Kushairi A, Varadhan KK, Krznaric Z, Kulkarni AD, et al. Perioperative probiotics or synbiotics in adults undergoing elective abdominal surgery: a systematic review and meta-analysis of randomized controlled trials. Ann Surg. 2020;271(6):1036\u201347. https:\/\/doi.org\/10.1097\/SLA.0000000000003581.","journal-title":"Ann Surg"},{"key":"1735_CR70","doi-asserted-by":"publisher","DOI":"10.1007\/s12602-019-09611-z","author":"J Casas-Sol\u00eds","year":"2019","unstructured":"Casas-Sol\u00eds J, Huizar-L\u00f3pez MDR, Irecta-N\u00e1jera CA, Pita-L\u00f3pez ML, Santerre A. Immunomodulatory effect of lactobacillus casei in a murine model of colon carcinogenesis. Probiotics Antimicrob Proteins. 2019. https:\/\/doi.org\/10.1007\/s12602-019-09611-z.","journal-title":"Probiotics Antimicrob Proteins"},{"issue":"1","key":"1735_CR71","first-page":"35","volume":"40","author":"B Krebs","year":"2016","unstructured":"Krebs B. Prebiotic and synbiotic treatment before colorectal surgery\u2013randomised double blind trial. Coll Antropol. 2016;40(1):35\u201340.","journal-title":"Coll Antropol"},{"issue":"12","key":"1735_CR72","doi-asserted-by":"publisher","first-page":"E340","DOI":"10.1177\/000313481307901202","volume":"79","author":"B Krebs","year":"2013","unstructured":"Krebs B, Horvat M, Golle A, Krznaric Z, Pape\u0161 D, Augustin G, et al. A randomized clinical trial of synbiotic treatment before colorectal cancer surgery. Am Surg. 2013;79(12):E340\u20132.","journal-title":"Am Surg"},{"issue":"3","key":"1735_CR73","doi-asserted-by":"publisher","first-page":"578","DOI":"10.3945\/ajcn.2009.28106","volume":"90","author":"DL Worthley","year":"2009","unstructured":"Worthley DL, Le Leu RK, Whitehall VL, Conlon M, Christophersen C, Belobrajdic D, et al. A human, double-blind, placebo-controlled, crossover trial of prebiotic, probiotic, and synbiotic supplementation: effects on luminal, inflammatory, epigenetic, and epithelial biomarkers of colorectal cancer. Am J Clin Nutr. 2009;90(3):578\u201386. https:\/\/doi.org\/10.3945\/ajcn.2009.28106.","journal-title":"Am J Clin Nutr"},{"issue":"5","key":"1735_CR74","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.3390\/cancers12051162","volume":"12","author":"P Lamichhane","year":"2020","unstructured":"Lamichhane P, Maiolini M, Alnafoosi O, Hussein S, Alnafoosi H, Umbela S, et al. Colorectal cancer and probiotics: are bugs really drugs? Cancers (Basel). 2020;12(5):1162. https:\/\/doi.org\/10.3390\/cancers12051162.","journal-title":"Cancers (Basel)"},{"issue":"6","key":"1735_CR75","doi-asserted-by":"publisher","first-page":"e0178870","DOI":"10.1371\/journal.pone.0178870","volume":"12","author":"MM Liu","year":"2017","unstructured":"Liu MM, Li ST, Shu Y, Zhan HQ. Probiotics for prevention of radiation-induced diarrhea: a meta-analysis of randomized controlled trials. PLoS ONE. 2017;12(6):e0178870. https:\/\/doi.org\/10.1371\/journal.pone.0178870.","journal-title":"PLoS ONE"},{"issue":"8","key":"1735_CR76","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/nrgastro.2017.75","volume":"14","author":"GR Gibson","year":"2017","unstructured":"Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, et al. Expert consensus document: the international scientific association for probiotics and prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14(8):491\u2013502. https:\/\/doi.org\/10.1038\/nrgastro.2017.75.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"8","key":"1735_CR77","doi-asserted-by":"publisher","first-page":"465","DOI":"10.3390\/nu8080465","volume":"8","author":"TR Qamar","year":"2016","unstructured":"Qamar TR, Syed F, Nasir M, Rehman H, Zahid MN, Liu RH, et al. Novel combination of prebiotics galacto-oligosaccharides and inulin-inhibited aberrant crypt foci formation and biomarkers of colon cancer in Wistar rats. Nutrients. 2016;8(8):465. https:\/\/doi.org\/10.3390\/nu8080465.","journal-title":"Nutrients"},{"issue":"11","key":"1735_CR78","doi-asserted-by":"publisher","first-page":"1884","DOI":"10.1158\/1055-9965","volume":"28","author":"MB Skiba","year":"2019","unstructured":"Skiba MB, Kohler LN, Crane TE, Jacobs ET, Shadyab AH, Kato I, et al. The association between prebiotic fiber supplement use and colorectal cancer risk and mortality in the women\u2019s health initiative. Cancer Epidemiol Biomark Prev. 2019;28(11):1884\u201390. https:\/\/doi.org\/10.1158\/1055-9965.","journal-title":"Cancer Epidemiol Biomark Prev"},{"issue":"6","key":"1735_CR79","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1080\/19490976.2020.1764309","volume":"11","author":"K Ka\u017amierczak-Siedlecka","year":"2020","unstructured":"Ka\u017amierczak-Siedlecka K, Daca A, Fic M, van de Wetering T, Folwarski M, Makarewicz W. Therapeutic methods of gut microbiota modification in colorectal cancer management\u2014fecal microbiota transplantation, prebiotics, probiotics, and synbiotics. Gut Microbes. 2020;11(6):1518\u201330. https:\/\/doi.org\/10.1080\/19490976.2020.1764309.","journal-title":"Gut Microbes"},{"issue":"8","key":"1735_CR80","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1017\/S0007114515002780","volume":"114","author":"N Eid","year":"2015","unstructured":"Eid N, Osmanova H, Natchez C, Walton G, Costabile A, Gibson G, et al. Impact of palm date consumption on microbiota growth and large intestinal health: a randomised, controlled, cross-over, human intervention study. Br J Nutr. 2015;114(8):1226\u201336. https:\/\/doi.org\/10.1017\/S0007114515002780.","journal-title":"Br J Nutr"},{"issue":"2","key":"1735_CR81","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1017\/S0007114515001750","volume":"114","author":"RK Le Leu","year":"2015","unstructured":"Le Leu RK, Winter JM, Christophersen CT, Young GP, Humphreys KJ, Hu Y, et al. Butyrylated starch intake can prevent red meat-induced O6-methyl-2-deoxyguanosine adducts in human rectal tissue: a randomised clinical trial. Br J Nutr. 2015;114(2):220\u201330. https:\/\/doi.org\/10.1017\/S0007114515001750.","journal-title":"Br J Nutr"},{"issue":"3","key":"1735_CR82","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1002\/ptr.5009","volume":"28","author":"AL Molan","year":"2014","unstructured":"Molan AL, Liu Z, Plimmer G. Evaluation of the effect of blackcurrant products on gut microbiota and on markers of risk for colon cancer in humans. Phytother Res. 2014;28(3):416\u201322. https:\/\/doi.org\/10.1002\/ptr.5009.","journal-title":"Phytother Res"},{"issue":"2","key":"1735_CR83","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1017\/S0007114514003523","volume":"113","author":"K Windey","year":"2015","unstructured":"Windey K, De Preter V, Huys G, Broekaert WF, Delcour JA, Louat T, et al. Wheat bran extract alters colonic fermentation and microbial composition, but does not affect faecal water toxicity: a randomised controlled trial in healthy subjects. Br J Nutr. 2015;113(2):225\u201338. https:\/\/doi.org\/10.1017\/S0007114514003523.","journal-title":"Br J Nutr"},{"issue":"7","key":"1735_CR84","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1001\/jamaoncol.2016.6374","volume":"3","author":"RS Mehta","year":"2017","unstructured":"Mehta RS, Nishihara R, Cao Y, Song M, Mima K, Qian ZR, et al. Association of dietary patterns with risk of colorectal cancer subtypes classified by Fusobacterium nucleatum in tumor tissue [published correction appears in JAMA Oncol. 2019;5(4):579]. JAMA Oncol. 2017;3(7):921\u20137. https:\/\/doi.org\/10.1001\/jamaoncol.2016.6374.","journal-title":"JAMA Oncol."},{"issue":"2","key":"1735_CR85","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1158\/1940-6207.CAPR-10-0215","volume":"4","author":"PJ Limburg","year":"2011","unstructured":"Limburg PJ, Mahoney MR, Ziegler KL, Sontag SJ, Schoen RE, Benya R, et al. Randomized phase II trial of sulindac, atorvastatin, and prebiotic dietary fiber for colorectal cancer chemoprevention. Cancer Prev Res (Phila). 2011;4(2):259\u201369. https:\/\/doi.org\/10.1158\/1940-6207.CAPR-10-0215.","journal-title":"Cancer Prev Res (Phila)"},{"issue":"1","key":"1735_CR86","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1080\/01635581.2015.976317","volume":"67","author":"OC Martin","year":"2015","unstructured":"Martin OC, Lin C, Naud N, Tache S, Raymond-Letron I, Corpet DE, et al. Antibiotic suppression of intestinal microbiota reduces heme-induced lipoperoxidation associated with colon carcinogenesis in rats. Nutr Cancer. 2015;67(1):119\u201325. https:\/\/doi.org\/10.1080\/01635581.2015.976317.","journal-title":"Nutr Cancer"},{"issue":"1","key":"1735_CR87","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.bbrc.2016.05.139","volume":"478","author":"H Ushijima","year":"2016","unstructured":"Ushijima H, Horyozaki A, Maeda M. Anisomycin-induced GATA-6 degradation accompanying a decrease of proliferation of colorectal cancer cell. Biochem Biophys Res Commun. 2016;478(1):481\u20135. https:\/\/doi.org\/10.1016\/j.bbrc.2016.05.139.","journal-title":"Biochem Biophys Res Commun"},{"issue":"7","key":"1735_CR88","doi-asserted-by":"publisher","first-page":"1989","DOI":"10.1158\/0008-5472.CAN-14-2430","volume":"76","author":"VV Prabhu","year":"2016","unstructured":"Prabhu VV, Hong B, Allen JE, Zhang S, Lulla AR, Dicker DT, et al. Small-molecule prodigiosin restores p53 tumor suppressor activity in chemoresistant colorectal cancer stem cells via c-Jun-mediated \u0394Np73 inhibition and p73 activation. Cancer Res. 2016;76(7):1989\u201399. https:\/\/doi.org\/10.1158\/0008-5472.CAN-14-2430.","journal-title":"Cancer Res"},{"issue":"1","key":"1735_CR89","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1186\/s12885-016-2879-8","volume":"16","author":"J Klose","year":"2016","unstructured":"Klose J, Eissele J, Volz C, Schmitt S, Ritter A, Ying S, et al. Salinomycin inhibits metastatic colorectal cancer growth and interferes with Wnt\/\u03b2-catenin signaling in CD133+ human colorectal cancer cells. BMC Cancer. 2016;16(1):896. https:\/\/doi.org\/10.1186\/s12885-016-2879-8.","journal-title":"BMC Cancer"},{"issue":"6369","key":"1735_CR90","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1126\/science.aal5240","volume":"358","author":"S Bullman","year":"2017","unstructured":"Bullman S, Pedamallu CS, Sicinska E, Clancy TE, Zhang X, Cai D, et al. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science. 2017;358(6369):1443\u20138. https:\/\/doi.org\/10.1126\/science.aal5240.","journal-title":"Science"},{"issue":"9","key":"1735_CR91","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1158\/1940-6207.CAPR-16-0095","volume":"9","author":"DC Montrose","year":"2016","unstructured":"Montrose DC, Zhou XK, McNally EM, Sue E, Yantiss RK, Gross SS, et al. Celecoxib alters the intestinal microbiota and metabolome in association with reducing polyp burden. Cancer Prev Res (Phila). 2016;9(9):721\u201331. https:\/\/doi.org\/10.1158\/1940-6207.CAPR-16-0095.","journal-title":"Cancer Prev Res (Phila)"},{"issue":"31","key":"1735_CR92","doi-asserted-by":"publisher","first-page":"32013","DOI":"10.18632\/oncotarget.5166","volume":"6","author":"YN Yu","year":"2015","unstructured":"Yu YN, Yu TC, Zhao HJ, Sun TT, Chen HM, Chen HY, et al. Berberine may rescue Fusobacterium nucleatum-induced colorectal tumorigenesis by modulating the tumor microenvironment. Oncotarget. 2015;6(31):32013\u201326. https:\/\/doi.org\/10.18632\/oncotarget.5166.","journal-title":"Oncotarget"},{"issue":"51","key":"1735_CR93","doi-asserted-by":"publisher","first-page":"85318","DOI":"10.18632\/oncotarget.13347","volume":"7","author":"M Wu","year":"2016","unstructured":"Wu M, Wu Y, Deng B, Li J, Cao H, Qu Y, et al. Isoliquiritigenin decreases the incidence of colitis-associated colorectal cancer by modulating the intestinal microbiota. Oncotarget. 2016;7(51):85318\u201331. https:\/\/doi.org\/10.18632\/oncotarget.13347.","journal-title":"Oncotarget"},{"issue":"11","key":"1735_CR94","doi-asserted-by":"publisher","first-page":"2483","DOI":"10.1097\/MIB.0000000000000522","volume":"21","author":"RM McFadden","year":"2015","unstructured":"McFadden RM, Larmonier CB, Shehab KW, Midura-Kiela M, Ramalingam R, Harrison CA, et al. The role of curcumin in modulating colonic microbiota during colitis and colon cancer prevention. Inflamm Bowel Dis. 2015;21(11):2483\u201394. https:\/\/doi.org\/10.1097\/MIB.0000000000000522.","journal-title":"Inflamm Bowel Dis"},{"issue":"1","key":"1735_CR95","first-page":"245","volume":"31","author":"G Tomasello","year":"2017","unstructured":"Tomasello G, Mazzola M, Jurjus A, Cappello F, Carini F, Damiani P, et al. The fingerprint of the human gastrointestinal tract microbiota: a hypothesis of molecular mapping. J Biol Regul Homeost Agents. 2017;31(1):245\u20139.","journal-title":"J Biol Regul Homeost Agents"},{"issue":"7","key":"1735_CR96","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1089\/omi.2014.0018","volume":"18","author":"M El Rakaiby","year":"2014","unstructured":"El Rakaiby M, Dutilh BE, Rizkallah MR, Boleij A, Cole JN, Aziz RK. Pharmacomicrobiomics: the impact of human microbiome variations on systems pharmacology and personalized therapeutics. OMICS. 2014;18(7):402\u201314. https:\/\/doi.org\/10.1089\/omi.2014.0018.","journal-title":"OMICS"},{"issue":"11","key":"1735_CR97","doi-asserted-by":"publisher","first-page":"2545","DOI":"10.1002\/ijc.30643","volume":"140","author":"H Cao","year":"2017","unstructured":"Cao H, Xu M, Dong W, Deng B, Wang S, Zhang Y, et al. Secondary bile acid-induced dysbiosis promotes intestinal carcinogenesis. Int J Cancer. 2017;140(11):2545\u201356. https:\/\/doi.org\/10.1002\/ijc.30643.","journal-title":"Int J Cancer"},{"issue":"2","key":"1735_CR98","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1101\/gr.126516.111","volume":"22","author":"M Castellarin","year":"2012","unstructured":"Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M, Strauss J, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012;22(2):299\u2013306. https:\/\/doi.org\/10.1101\/gr.126516.111.","journal-title":"Genome Res"},{"key":"1735_CR99","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.radonc.2020.01.011","volume":"143","author":"X Ding","year":"2020","unstructured":"Ding X, Li Q, Li P, Chen X, Xiang L, Bi L, et al. Fecal microbiota transplantation: A promising treatment for radiation enteritis? Radiother Oncol. 2020;143:12\u20138. https:\/\/doi.org\/10.1016\/j.radonc.2020.01.011.","journal-title":"Radiother Oncol"},{"issue":"1","key":"1735_CR100","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s40168-020-00845-6","volume":"8","author":"HW Xiao","year":"2020","unstructured":"Xiao HW, Cui M, Li Y, Dong JL, Zhang SQ, Zhu CC, et al. Gut microbiota-derived indole 3-propionic acid protects against radiation toxicity via retaining acyl-CoA-binding protein. Microbiome. 2020;8(1):69. https:\/\/doi.org\/10.1186\/s40168-020-00845-6.","journal-title":"Microbiome"},{"issue":"2","key":"1735_CR101","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/mi.2013.117","volume":"7","author":"EG Pamer","year":"2014","unstructured":"Pamer EG. Fecal microbiota transplantation: effectiveness, complexities, and lingering concerns. Mucosal Immunol. 2014;7(2):210\u20134. https:\/\/doi.org\/10.1038\/mi.2013.117.","journal-title":"Mucosal Immunol"},{"issue":"8","key":"1735_CR102","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1007\/s11894-013-0337-1","volume":"15","author":"TJ Borody","year":"2013","unstructured":"Borody TJ, Paramsothy S, Agrawal G. Fecal microbiota transplantation: indications, methods, evidence, and future directions. Curr Gastroenterol Rep. 2013;15(8):337. https:\/\/doi.org\/10.1007\/s11894-013-0337-1.","journal-title":"Curr Gastroenterol Rep"},{"issue":"6369","key":"1735_CR103","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.1126\/science.aaq0034","volume":"358","author":"D Hoffmann","year":"2017","unstructured":"Hoffmann D, Palumbo F, Ravel J, Roghmann MC, Rowthorn V, von Rosenvinge E. Improving regulation of microbiota transplants. Science. 2017;358(6369):1390\u20131. https:\/\/doi.org\/10.1126\/science.aaq0034.","journal-title":"Science"},{"issue":"2","key":"1735_CR104","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/s41592-018-0301-y","volume":"16","author":"C Ronda","year":"2019","unstructured":"Ronda C, Chen SP, Cabral V, Yaung SJ, Wang HH. Metagenomic engineering of the mammalian gut microbiome in situ. Nat Methods. 2019;16(2):167\u201370. https:\/\/doi.org\/10.1038\/s41592-018-0301-y.","journal-title":"Nat Methods"},{"issue":"12","key":"1735_CR105","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1038\/s41565-019-0589-5","volume":"14","author":"W Song","year":"2019","unstructured":"Song W, Anselmo AC, Huang L. Nanotechnology intervention of the microbiome for cancer therapy. Nat Nanotechnol. 2019;14(12):1093\u2013103. https:\/\/doi.org\/10.1038\/s41565-019-0589-5.","journal-title":"Nat Nanotechnol"},{"issue":"7","key":"1735_CR106","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1038\/s41591-019-0498-z","volume":"25","author":"S Chowdhury","year":"2019","unstructured":"Chowdhury S, Castro S, Coker C, Hinchliffe TE, Arpaia N, Danino T. Programmable bacteria induce durable tumor regression and systemic antitumor immunity. Nat Med. 2019;25(7):1057\u201363. https:\/\/doi.org\/10.1038\/s41591-019-0498-z.","journal-title":"Nat Med"},{"key":"1735_CR107","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1146\/annurev-food-030216-030256","volume":"8","author":"B Sola-Oladokun","year":"2017","unstructured":"Sola-Oladokun B, Culligan EP, Sleator RD. Engineered probiotics: applications and biological containment. Annu Rev Food Sci Technol. 2017;8:353\u201370. https:\/\/doi.org\/10.1146\/annurev-food-030216-030256.","journal-title":"Annu Rev Food Sci Technol"},{"issue":"7575","key":"1735_CR108","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1038\/nature15524","volume":"526","author":"S Kommineni","year":"2015","unstructured":"Kommineni S, Bretl DJ, Lam V, Chakraborty R, Hayward M, Simpson P, et al. Bacteriocin production augments niche competition by enterococci in the mammalian gastrointestinal tract. Nature. 2015;526(7575):719\u201322. https:\/\/doi.org\/10.1038\/nature15524.","journal-title":"Nature"},{"issue":"15","key":"1735_CR109","doi-asserted-by":"publisher","first-page":"6299","DOI":"10.1007\/s00253-018-9098-y","volume":"102","author":"B \u00d6zel","year":"2018","unstructured":"\u00d6zel B, \u015eim\u015fek \u00d6, Ak\u00e7elik M, Saris PEJ. Innovative approaches to nisin production. Appl Microbiol Biotechnol. 2018;102(15):6299\u2013307. https:\/\/doi.org\/10.1007\/s00253-018-9098-y.","journal-title":"Appl Microbiol Biotechnol"},{"issue":"37","key":"1735_CR110","doi-asserted-by":"publisher","first-page":"18571","DOI":"10.1073\/pnas.1906653116","volume":"116","author":"K Suwan","year":"2019","unstructured":"Suwan K, Yata T, Waramit S, Przystal JM, Stoneham CA, Bentayebi K, et al. Next-generation of targeted AAVP vectors for systemic transgene delivery against cancer. Proc Natl Acad Sci USA. 2019;116(37):18571\u20137. https:\/\/doi.org\/10.1073\/pnas.1906653116.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"8","key":"1735_CR111","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1038\/nrd4695","volume":"14","author":"K Kingwell","year":"2015","unstructured":"Kingwell K. Bacteriophage therapies re-enter clinical trials. Nat Rev Drug Discov. 2015;14(8):515\u20136. https:\/\/doi.org\/10.1038\/nrd4695.","journal-title":"Nat Rev Drug Discov"},{"issue":"12","key":"1735_CR112","doi-asserted-by":"publisher","first-page":"960","DOI":"10.15252\/msb.20177589","volume":"13","author":"PI Costea","year":"2017","unstructured":"Costea PI, Coelho LP, Sunagawa S, Munch R, Huerta-Cepas J, Forslund K, et al. Subspecies in the global human gut microbiome. Mol Syst Biol. 2017;13(12):960. https:\/\/doi.org\/10.15252\/msb.20177589.","journal-title":"Mol Syst Biol"},{"issue":"4","key":"1735_CR113","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/s41591-019-0406-6","volume":"25","author":"J Wirbel","year":"2019","unstructured":"Wirbel J, Pyl PT, Kartal E, Zych K, Kashani A, Milanese A, et al. Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat Med. 2019;25(4):679\u201389. https:\/\/doi.org\/10.1038\/s41591-019-0406-6.","journal-title":"Nat Med"},{"issue":"6","key":"1735_CR114","doi-asserted-by":"publisher","first-page":"2370","DOI":"10.1021\/acs.jproteome.9b00054","volume":"18","author":"X Zhang","year":"2019","unstructured":"Zhang X, Figeys D. Perspective and guidelines for metaproteomics in microbiome studies. J Proteome Res. 2019;18(6):2370\u201380. https:\/\/doi.org\/10.1021\/acs.jproteome.9b00054.","journal-title":"J Proteome Res"},{"issue":"7758","key":"1735_CR115","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1038\/s41586-019-1237-9","volume":"569","author":"J Lloyd-Price","year":"2019","unstructured":"Lloyd-Price J, Arze C, Ananthakrishnan AN, Schirmer M, Avila-Pacheco J, Poon TW, et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature. 2019;569(7758):655\u201362. https:\/\/doi.org\/10.1038\/s41586-019-1237-9.","journal-title":"Nature"},{"issue":"5","key":"1735_CR116","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1007\/s12275-020-9365-3","volume":"58","author":"EK Yimagou","year":"2020","unstructured":"Yimagou EK, Baudoin JP, Abdallah RA, Di Pinto F, Bou Khalil JY, Raoult D. Full-repertoire comparison of the microscopic objects composing the human gut microbiome with sequenced and cultured communities. J Microbiol. 2020;58(5):377\u201386. https:\/\/doi.org\/10.1007\/s12275-020-9365-3.","journal-title":"J Microbiol"},{"issue":"2","key":"1735_CR117","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1111\/imm.12933","volume":"154","author":"S Haase","year":"2018","unstructured":"Haase S, Haghikia A, Wilck N, M\u00fcller DN, Linker RA. Impacts of microbiome metabolites on immune regulation and autoimmunity. Immunology. 2018;154(2):230\u20138. https:\/\/doi.org\/10.1111\/imm.12933.","journal-title":"Immunology"},{"issue":"3","key":"1735_CR118","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1080\/19490976.2015.1134082","volume":"7","author":"DJ Morrison","year":"2016","unstructured":"Morrison DJ, Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes. 2016;7(3):189\u2013200. https:\/\/doi.org\/10.1080\/19490976.2015.1134082.","journal-title":"Gut Microbes"}],"container-title":["Radiation Oncology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13014-020-01735-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13014-020-01735-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13014-020-01735-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T20:06:56Z","timestamp":1610482016000},"score":1,"resource":{"primary":{"URL":"https:\/\/ro-journal.biomedcentral.com\/articles\/10.1186\/s13014-020-01735-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,13]]},"references-count":118,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1735"],"URL":"https:\/\/doi.org\/10.1186\/s13014-020-01735-9","relation":{},"ISSN":["1748-717X"],"issn-type":[{"value":"1748-717X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,13]]},"assertion":[{"value":"17 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"9"}}