Roles of microbiota in pancreatic cancer development and treatment

References

• Kleeff J, Korc M, Apte M, La Vecchia C, Johnson CD, Biankin AV, Neale RE, Tempero M, Tuveson DA, Hruban RH. et al. Pancreatic cancer. Nat Rev Dis Primers. 2016;2(1):1–22. doi:10.1038/nrdp.2016.22.
   Google Scholar
• Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17–48. doi:10.3322/caac.21763.
   PubMed Web of Science ®Google Scholar
• Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul J-L, Choné L, Francois E, Artru P, Biagi JJ. et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018;379(25):2395–2406. doi:10.1056/NEJMoa1809775.
   PubMed Web of Science ®Google Scholar
• Ducreux M, Cuhna AS, Caramella C, Hollebecque A, Burtin P, Goéré D, Seufferlein T, Haustermans K, Van Laethem JL, Conroy T. et al. Cancer of the pancreas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26:v56–v68. doi:10.1093/annonc/mdv295.
   PubMed Web of Science ®Google Scholar
• Crane CH, Varadhachary GR, Yordy JS, Staerkel GA, Javle MM, Safran H, Haque W, Hobbs BD, Krishnan S, Fleming JB. et al. Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression. J Clin Oncol. 2011;29(22):3037–3043. doi:10.1200/JCO.2010.33.8038.
   PubMed Web of Science ®Google Scholar
• Mukherjee S, Hurt CN, Bridgewater J, Falk S, Cummins S, Wasan H, Crosby T, Jephcott C, Roy R, Radhakrishna G. et al. Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase 2 trial. Lancet Oncol. 2013;14(4):317–326. doi:10.1016/S1470-2045(13)70021-4.
   PubMed Web of Science ®Google Scholar
• Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul J-L, Gourgou-Bourgade S, de la Fouchardière C. et al. FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer. N Engl J Med. 2011;364(19):1817–1825. doi:10.1056/NEJMoa1011923.
   PubMed Web of Science ®Google Scholar
• Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN. et al. Increased survival in pancreatic cancer with nab-paclitaxel plus Gemcitabine. N Engl J Med. 2013;369(18):1691–1703. doi:10.1056/NEJMoa1304369.
   PubMed Web of Science ®Google Scholar
• Sohal DPS, Kennedy EB, Khorana A, Copur MS, Crane CH, Garrido-Laguna I, Krishnamurthi S, Moravek C, O’Reilly EM, Philip PA. et al. Metastatic pancreatic cancer: ASCO clinical practice guideline update. J Clin Oncol. 2018;36(24):2545–2556. doi:10.1200/JCO.2018.78.9636.
   PubMed Web of Science ®Google Scholar
• Zeng S. Chemoresistance in pancreatic cancer. Int J Mol Sci. 2019;20(18):4504–4519. doi:10.3390/ijms20184504.
   PubMed Web of Science ®Google Scholar
• O’Reilly EM, Oh D-Y, Dhani N, Renouf DJ, Lee MA, Sun W, Fisher G, Hezel A, Chang S-C, Vlahovic G. et al. Durvalumab with or without tremelimumab for patients with metastatic pancreatic ductal adenocarcinoma: a phase 2 randomized clinical trial. JAMA Oncol. 2019;5(10):1431–1438. doi:10.1001/jamaoncol.2019.1588.
   PubMed Web of Science ®Google Scholar
• Ho WJ, Jaffee EM, Zheng L. The tumour microenvironment in pancreatic cancer — clinical challenges and opportunities. Nat Rev Clin Oncol. 2020;17(9):527–540. doi:10.1038/s41571-020-0363-5.
   PubMed Web of Science ®Google Scholar
• Espinet E, Klein L, Puré E, Singh SK. Mechanisms of PDAC subtype heterogeneity and therapy response. Trends Cancer. 2022;8(12):1060–1071. doi:10.1016/j.trecan.2022.08.005.
   PubMed Web of Science ®Google Scholar
• Ferreira RMM, Sancho R, Messal HA, Nye E, Spencer-Dene B, Stone RK, Stamp G, Rosewell I, Quaglia A, Behrens A. et al. Duct- and acinar-derived pancreatic ductal adenocarcinomas show distinct tumor progression and marker expression. Cell Rep. 2017;21(4):966–978. doi:10.1016/j.celrep.2017.09.093.
   PubMed Web of Science ®Google Scholar
• Lee AYL, Dubois CL, Sarai K, Zarei S, Schaeffer DF, Sander M, Kopp JL. Cell of origin affects tumour development and phenotype in pancreatic ductal adenocarcinoma. Gut. 2019;68(3):487–498. doi:10.1136/gutjnl-2017-314426.
   PubMed Web of Science ®Google Scholar
• Flowers BM, Xu H, Mulligan AS, Hanson KJ, Seoane JA, Vogel H, Curtis C, Wood LD, Attardi LD. Cell of origin influences pancreatic cancer subtype. Cancer Discov. 2021;11(3):660–677. doi:10.1158/2159-8290.CD-20-0633.
   PubMed Web of Science ®Google Scholar
• Habbe N, Shi G, Meguid RA, Fendrich V, Esni F, Chen H, Feldmann G, Stoffers DA, Konieczny SF, Leach SD. et al. Spontaneous induction of murine pancreatic intraepithelial neoplasia (mPanIN) by acinar cell targeting of oncogenic Kras in adult mice. Proc Natl Acad Sci U S A. 2008;105(48):18913–18918. doi:10.1073/pnas.0810097105.
   PubMed Web of Science ®Google Scholar
• Hu HF, Ye Z, Qin Y, Xu X-W, Yu X-J, Zhuo Q-F, Ji S-R. Mutations in key driver genes of pancreatic cancer: molecularly targeted therapies and other clinical implications. Acta Pharmacol Sin. 2021;42(11):1725–1741. doi:10.1038/s41401-020-00584-2.
   PubMed Web of Science ®Google Scholar
• Afzaal M, Saeed F, Shah YA, Hussain M, Rabail R, Socol CT, Hassoun A, Pateiro M, Lorenzo JM, Rusu AV. et al. Human gut microbiota in health and disease: unveiling the relationship. Front Microbiol. 2022;13:1–14. doi:10.3389/fmicb.2022.999001.
   Web of Science ®Google Scholar
• Zhang T, Gao G, Sakandar HA, Kwok LY, Sun Z. Gut dysbiosis in pancreatic diseases: a causative factor and a novel therapeutic target. Front Nutr. 2022;9:1–20. doi:10.3389/fnut.2022.814269.
   Web of Science ®Google Scholar
• Pushalkar S, Hundeyin M, Daley D, Zambirinis CP, Kurz E, Mishra A, Mohan N, Aykut B, Usyk M, Torres LE. et al. The pancreatic cancer microbiome promotes oncogenesis by induction of innate and adaptive immune suppression. Cancer Discov. 2018;8(4):403–416. doi:10.1158/2159-8290.CD-17-1134.
   PubMed Web of Science ®Google Scholar
• Thomas RM, Gharaibeh RZ, Gauthier J, Beveridge M, Pope JL, Guijarro MV, Yu Q, He Z, Ohland C, Newsome R. et al. Intestinal microbiota enhances pancreatic carcinogenesis in preclinical models. Carcinogenesis. 2018;39(8):1068–1078. doi:10.1093/carcin/bgy073.
   PubMed Web of Science ®Google Scholar
• Sethi V, Kurtom S, Tarique M, Lavania S, Malchiodi Z, Hellmund L, Zhang L, Sharma U, Giri B, Garg B. et al. Gut microbiota promotes tumor growth in mice by modulating immune response. Gastroenterology. 2018;155(1):33–37.e6. doi:10.1053/j.gastro.2018.04.001.
   PubMed Web of Science ®Google Scholar
• Geller LT, Barzily-Rokni M, Danino T, Jonas OH, Shental N, Nejman D, Gavert N, Zwang Y, Cooper ZA, Shee K. et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science. 2017;1160(6356):1156–1160. doi:10.1126/science.aah5043.
   Google Scholar
• Tintelnot J, Xu Y, Lesker TR, Schönlein M, Konczalla L, Giannou AD, Pelczar P, Kylies D, Puelles VG, Bielecka AA. et al. Microbiota-derived 3-IAA influences chemotherapy efficacy in pancreatic cancer. Nature. 2023;615(7950):168–174. doi:10.1038/s41586-023-05728-y.
   PubMed Web of Science ®Google Scholar
• Farrell JJ, Zhang L, Zhou H, Chia D, Elashoff D, Akin D, Paster BJ, Joshipura K, Wong DTW. Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer. Gut. 2012;61(4):582–588. doi:10.1136/gutjnl-2011-300784.
   PubMed Web of Science ®Google Scholar
• Olson SH, Satagopan J, Xu Y, Ling L, Leong S, Orlow I, Saldia A, Li P, Nunes P, Madonia V. et al. The oral microbiota in patients with pancreatic cancer, patients with IPMNs, and controls: a pilot study. Cancer Causes Control. 2017;28(9):959–969. doi:10.1007/s10552-017-0933-8.
   PubMed Web of Science ®Google Scholar
• Vogtmann E, Han Y, Caporaso JG, Bokulich N, Mohamadkhani A, Moayyedkazemi A, Hua X, Kamangar F, Wan Y, Suman S. et al. Oral microbial community composition is associated with pancreatic cancer: a case-control study in Iran. Cancer Med. 2020;9(2):797–806. doi:10.1002/cam4.2660.
   PubMed Web of Science ®Google Scholar
• Wei A-L, Mao L, Wei-Ming H, Zhen-Lu L, Yuan J, Liu H-Y, Zhou L-L, Li K, Ang L, Rosemary Fu M. et al. Oral microbiome and pancreatic cancer. WJG. 2020;9327(48):7679–7692. doi:10.3748/wjg.v26.i48.7679.
   Google Scholar
• Nagata N, Nishijima S, Kojima Y, Hisada Y, Imbe K, Miyoshi-Akiyama T, Suda W, Kimura M, Aoki R, Sekine K. et al. Metagenomic identification of microbial signatures predicting pancreatic cancer from a multinational study. Gastroenterology. 2022;163(1):222–238. doi:10.1053/j.gastro.2022.03.054.
   PubMed Web of Science ®Google Scholar
• Kartal E, Schmidt TSB, Molina-Montes E, Rodríguez-Perales S, Wirbel J, Maistrenko OM, Akanni WA, Alashkar Alhamwe B, Alves RJ, Carrato A. et al. A faecal microbiota signature with high specificity for pancreatic cancer. Gut. 2022;71(7):1359–1372. doi:10.1136/gutjnl-2021-324755.
   PubMed Web of Science ®Google Scholar
• Lu H, Ren Z, Li A, Li J, Xu S, Zhang H, Jiang J, Yang J, Luo Q, Zhou K. et al. Tongue coating microbiome data distinguish patients with pancreatic head cancer from healthy controls. J Oral Microbiol. 2019;11(1):1563409. doi:10.1080/20002297.2018.1563409.
   PubMed Web of Science ®Google Scholar
• Fan X, Alekseyenko AV, Wu J, Peters BA, Jacobs EJ, Gapstur SM, Purdue MP, Abnet CC, Stolzenberg-Solomon R, Miller G. et al. Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study. Gut. 2018;67(1):120–127. doi:10.1136/gutjnl-2016-312580.
   PubMed Web of Science ®Google Scholar
• Petrick JL, Wilkinson JE, Michaud DS, Cai Q, Gerlovin H, Signorello LB, Wolpin BM, Ruiz-Narváez EA, Long J, Yang Y. et al. The oral microbiome in relation to pancreatic cancer risk in African Americans. Br J Cancer. 2022;126(2):287–296. doi:10.1038/s41416-021-01578-5.
   PubMed Web of Science ®Google Scholar
• Michaud DS, Joshipura K, Giovannucci E, Fuchs CS. A prospective study of periodontal disease and pancreatic cancer in US male health professionals. J Natl Cancer Inst. 2007;99(2):171–175. doi:10.1093/jnci/djk021.
   PubMedGoogle Scholar
• Yu J, Ploner A, Chen MS, Zhang J, Sandborgh-Englund G, Ye W. Poor dental health and risk of pancreatic cancer: a nationwide registry-based cohort study in Sweden, 2009–2016. Br J Cancer. 2022;127(12):2133–2140. doi:10.1038/s41416-022-02018-8.
   PubMed Web of Science ®Google Scholar
• Michaud DS, Izard J, Wilhelm-Benartzi CS, You D-H, Grote VA, Tjønneland A, Dahm CC, Overvad K, Jenab M, Fedirko V. et al. Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study. Gut. 2013;62(12):1764–1770. doi:10.1136/gutjnl-2012-303006.
   PubMed Web of Science ®Google Scholar
• Huang J, Roosaar A, Axéll T, Ye W. A prospective cohort study on poor oral hygiene and pancreatic cancer risk. Int J Cancer. 2016;138(2):340–347. doi:10.1002/ijc.29710.
   PubMed Web of Science ®Google Scholar
• Chung L-M, Liang J-A, Lin C-L, Sun L-M, Kao C-H. Cancer risk in patients with candidiasis: a nationwide population-based cohort study. Oncotarget. 2017;8(38):63562–63573. doi:10.18632/oncotarget.18855.
   PubMedGoogle Scholar
• Wei A, Zhao H, Cong X, Wang L, Chen Y, Gou J, Hu Z, Hu X, Tian Y, Li K. et al. Oral mycobiota and pancreatic ductal adenocarcinoma. BMC Cancer. 2022;22(1):1–13. doi:10.1186/s12885-022-10329-5.
   PubMed Web of Science ®Google Scholar
• Hall MW, Singh N, Ng KF, Lam DK, Goldberg MB, Tenenbaum HC, Neufeld JD, G Beiko R, Senadheera DB. Inter-personal diversity and temporal dynamics of dental, tongue, and salivary microbiota in the healthy oral cavity. Npj Biofilms Microbiomes. 2017;3(1):0–1. doi:10.1038/s41522-016-0011-0.
   Google Scholar
• Wu J, Peters BA, Dominianni C, Zhang Y, Pei Z, Yang L, Ma Y, Purdue MP, Jacobs EJ, Gapstur SM. et al. Cigarette smoking and the oral microbiome in a large study of American adults. ISME J. 2016;10(10):2435–2446. doi:10.1038/ismej.2016.37.
   PubMed Web of Science ®Google Scholar
• Ren Z, Jiang J, Xie H, Li A, Lu H, Xu S, Zhou L, Zhang H, Cui G, Chen X. et al. Gut microbial profile analysis by MiSeq sequencing of pancreatic carcinoma patients in China. Oncotarget. 2017;8(56):95176–95191. doi:10.18632/oncotarget.18820.
   PubMedGoogle Scholar
• Zhou W, Zhang D, Li Z, Jiang H, Li J, Ren R, Gao X, Li J, Wang X, Wang W. et al. The fecal microbiota of patients with pancreatic ductal adenocarcinoma and autoimmune pancreatitis characterized by metagenomic sequencing. J Transl Med. 2021;19(1):1–12. doi:10.1186/s12967-021-02882-7.
   PubMed Web of Science ®Google Scholar
• Half E, Keren N, Reshef L, Dorfman T, Lachter I, Kluger Y, Reshef N, Knobler H, Maor Y, Stein A. et al. Fecal microbiome signatures of pancreatic cancer patients. Sci Rep. 2019;9(1):1–12. doi:10.1038/s41598-019-53041-4.
   PubMedGoogle Scholar
• Nejman D, Livyatan I, Fuks G, Gavert N, Zwang Y, Geller LT, Rotter-Maskowitz A, Weiser R, Mallel G, Gigi E. et al. The human tumor microbiome is composed of tumor type–specific intracellular bacteria. Science. 2020;368(6494):973–980. doi:10.1126/science.aay9189.
   PubMed Web of Science ®Google Scholar
• Del Castillo E, Meier R, Chung M, Koestler DC, Chen T, Paster BJ, Charpentier KP, Kelsey KT, Izard J, Michaud DS. et al. The microbiomes of pancreatic and duodenum tissue overlap and are highly subject specific but differ between pancreatic cancer and noncancer subjects. Cancer Epidemiol Biomarkers Prev. 2019;28(2):370–383. doi:10.1158/1055-9965.EPI-18-0542.
   PubMed Web of Science ®Google Scholar
• Aykut B, Pushalkar S, Chen R, Li Q, Abengozar R, Kim JI, Shadaloey SA, Wu D, Preiss P, Verma N. et al. The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL. Nature. 2019;574(7777):264–267. doi:10.1038/s41586-019-1608-2.
   PubMed Web of Science ®Google Scholar
• Tan Q, Ma X, Yang B, Liu Y, Xie Y, Wang X, Yuan W, Ma J. Periodontitis pathogen porphyromonas gingivalis promotes pancreatic tumorigenesis via neutrophil elastase from tumor-associated neutrophils. Gut Microbes. 2022;14(1). doi:10.1080/19490976.2022.2073785.
   Web of Science ®Google Scholar
• Sethi V, Vitiello GA, Saxena D, Miller G, Dudeja V. The role of the microbiome in immunologic development and its implication for pancreatic cancer immunotherapy. Gastroenterology. 2019;156(7):2097–2115.e2. doi:10.1053/j.gastro.2018.12.045.
   PubMed Web of Science ®Google Scholar
• Diehl GE, Longman RS, Zhang J-X, Breart B, Galan C, Cuesta A, Schwab SR, Littman DR. Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX 3 CR1 hi cells. Nature. 2013;494(7435):116–120. doi:10.1038/nature11809.
   PubMed Web of Science ®Google Scholar
• Thomas RM, Jobin C. Microbiota in pancreatic health and disease: the next frontier in microbiome research. Nat Rev Gastroenterol Hepatol. 2020;17(1):53–64. doi:10.1038/s41575-019-0242-7.
   PubMed Web of Science ®Google Scholar
• Ahuja M, Schwartz DM, Tandon M, Son A, Zeng M, Swaim W, Eckhaus M, Hoffman V, Cui Y, Xiao B. et al. Orai1-mediated antimicrobial secretion from pancreatic acini shapes the gut microbiome and regulates gut innate immunity. Cell Metab. 2017;25(3):635–646. doi:10.1016/j.cmet.2017.02.007.
   PubMed Web of Science ®Google Scholar
• Huang Y, Zhu N, Zheng X, Liu Y, Lu H, Yin X, Hao H, Tan Y, Wang D, Hu H. et al. Intratumor microbiome analysis identifies positive association between megasphaera and survival of Chinese patients with pancreatic ductal adenocarcinomas. Front Immunol. 2022;13:1–12. doi:10.3389/fimmu.2022.785422.
   Web of Science ®Google Scholar
• Mitsuhashi K, Nosho K, Sukawa Y, Matsunaga Y, Ito M, Kurihara H, Kanno S, Igarashi H, Naito T, Adachi Y. et al. Association of fusobacterium species in pancreatic cancer tissues with molecular features and prognosis. Oncotarget. 2015;6(9):7209–7220. doi:10.18632/oncotarget.3109.
   PubMedGoogle Scholar
• Gaiser RA, Halimi A, Alkharaan H, Lu L, Davanian H, Healy K, Hugerth LW, Ateeb Z, Valente R, Fernández Moro C. et al. Enrichment of oral microbiota in early cystic precursors to invasive pancreatic cancer. Gut. 2019;68(12):2186–2194. doi:10.1136/gutjnl-2018-317458.
   PubMed Web of Science ®Google Scholar
• Riquelme E, Zhang Y, Zhang L, Montiel M, Zoltan M, Dong W, Quesada P, Sahin I, Chandra V, San Lucas A. et al. Tumor microbiome diversity and composition article tumor microbiome diversity and composition influence pancreatic cancer outcomes. Cell. 2019;178(4):795–806.e12. doi:10.1016/j.cell.2019.07.008.
   PubMed Web of Science ®Google Scholar
• Guo W, Zhang Y, Guo S, Mei Z, Liao H, Dong H, Wu K, Ye H, Zhang Y, Zhu Y. et al. Tumor microbiome contributes to an aggressive phenotype in the basal-like subtype of pancreatic cancer. Commun Biol. 2021;4(1):1019. doi:10.1038/s42003-021-02557-5.
   PubMed Web of Science ®Google Scholar
• Narunsky-Haziza L, Sepich-Poore GD, Livyatan I, Asraf O, Martino C, Nejman D, Gavert N, Stajich JE, Amit G, González A. et al. Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions. Cell. 2022;185(20):3789–3806.e17. doi:10.1016/j.cell.2022.09.005.
   PubMed Web of Science ®Google Scholar
• Alam A, Levanduski E, Denz P, Villavicencio HS, Bhatta M, Alhorebi L, Zhang Y, Gomez EC, Morreale B, Senchanthisai S. et al. Article fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer ll article fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer. Cancer Cell. 2022;40(2):153–167.e11. doi:10.1016/j.ccell.2022.01.003.
   PubMed Web of Science ®Google Scholar
• Eckhoff AM, Fletcher AA, Kelly MS, Dohlman A, McIntyre CA, Shen X, Iyer MK, Nussbaum DP, Allen PJ. Comprehensive assessment of the intrinsic pancreatic microbiome. bioRxiv. 2023;2023(8):12.553074. doi:10.1101/2023.08.12.553074.
   Google Scholar
• Poore GD, Kopylova E, Zhu Q, Carpenter C, Fraraccio S, Wandro S, Kosciolek T, Janssen S, Metcalf J, Song SJ. et al. Microbiome analyses of blood and tissues suggest cancer diagnostic approach. Nature. 2020;579(7800):567–574. doi:10.1038/s41586-020-2095-1.
   PubMed Web of Science ®Google Scholar
• Gihawi A, Ge Y, Lu J, Puiu D, Xu A, Cooper CS, Brewer DS, Pertea M, Salzberg SL. Major data analysis errors invalidate cancer microbiome findings. Am Soc Microbiol. 2023;14(5):e01607–23. doi:10.1128/mbio.01607-23.
   Google Scholar
• Fletcher AA, Kelly MS, Eckhoff AM, Allen PJ. Revisiting the intrinsic mycobiome in pancreatic cancer. Nature. 2023;620(7972):E1–E6. doi:10.1038/s41586-023-06292-1.
   PubMed Web of Science ®Google Scholar
• Rubinstein MR, Wang X, Liu W, Hao Y, Cai G, Han Y. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-Cadherin/β-catenin signaling via its FadA Adhesin. Cell Host Microbe. 2013;14(2):195–206. doi:10.1016/j.chom.2013.07.012.
   PubMed Web of Science ®Google Scholar
• Bullman S, Pedamallu CS, Sicinska E, Clancy TE, Zhang X, Cai D, Neuberg D, Huang K, Guevara F, Nelson T. et al. Analysis of fusobacterium persistence and antibiotic response in colorectal cancer. Science. 2017;358(6369):1443–1448. doi:10.1126/science.aal5240.
   PubMed Web of Science ®Google Scholar
• Amieva M, Peek RM. Pathobiology of Helicobacter pylori–induced gastric cancer. Gastroenterology. 2016;150(1):64–78. doi:10.1053/j.gastro.2015.09.004.
   PubMed Web of Science ®Google Scholar
• Udayasuryan B, Ahmad RN, Nguyen TT&, Umaña A, Monét Roberts L, Sobol P, Jones SD, Munson JM, Slade DJ, Verbridge SS. et al. Fusobacterium nucleatum induces proliferation and migration in pancreatic cancer cells through host autocrine and paracrine signaling. Sci Signal. 2022;15(756):eabn4948. doi:10.1126/scisignal.abn4948.
   PubMed Web of Science ®Google Scholar
• Coker OO, Nakatsu G, Dai RZ, Wu WKK, Wong SH, Ng SC, Chan FKL, Sung JJY, Yu J. Enteric fungal microbiota dysbiosis and ecological alterations in colorectal cancer. Gut. 2019;68(4):654–662. doi:10.1136/gutjnl-2018-317178.
   PubMed Web of Science ®Google Scholar
• Sam QH, Chang MW, Chai LYA. The fungal mycobiome and its interaction with gut bacteria in the host. Int J Mol Sci. 2017;18(2):330. doi:10.3390/ijms18020330.
   PubMed Web of Science ®Google Scholar
• Iida N, Dzutsev A, Stewart CA, Smith L, Bouladoux N, Weingarten RA, Molina DA, Salcedo R, Back T, Cramer S. et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science. 2013;342(6161):967–970. doi:10.1126/science.1240527.
   PubMed Web of Science ®Google Scholar
• 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):356–365. doi:10.1038/nrgastro.2017.20.
   PubMed Web of Science ®Google Scholar
• García-González AP, Ritter AD, Shrestha S, Andersen EC, Yilmaz LS, Walhout AJM. Bacterial metabolism affects the C. elegans response to cancer chemotherapeutics. Cell. 2017;169(3):431–441.e8. doi:10.1016/j.cell.2017.03.046.
   PubMed Web of Science ®Google Scholar
• Scott TA, Quintaneiro LM, Norvaisas P, Lui PP, Wilson MP, Leung K-Y, Herrera-Dominguez L, Sudiwala S, Pessia A, Clayton PT. et al. Host-miCrobe co-metabolism dictates cancer drug efficacy in C. elegans. Cell. 2017;169(3):442–456.e18. doi:10.1016/j.cell.2017.03.040.
   PubMed Web of Science ®Google Scholar
• Yu TC, Guo F, Yu Y, Sun T, Ma D, Han J, Qian Y, Kryczek I, Sun D, Nagarsheth N. et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell. 2017;170(3):548–563.e16. doi:10.1016/j.cell.2017.07.008.
   PubMed Web of Science ®Google Scholar
• Zhang S, Yang Y, Weng W, Guo B, Cai G, Ma Y, Cai S. Fusobacterium nucleatum promotes chemoresistance to 5-fluorouracil by upregulation of BIRC3 expression in colorectal cancer. J Exp Clin Cancer Res. 2019;38(1):1–13. doi:10.1186/s13046-018-0985-y.
   PubMedGoogle Scholar
• Imai H, Saijo K, Komine K, Yoshida Y, Sasaki K, Suzuki A, Ouchi K, Takahashi M, Takahashi S, Shirota H. et al. Antibiotics improve the treatment efficacy of oxaliplatin-based but not irinotecan-based therapy in advanced colorectal cancer patients. J Oncol. 2020;2020:1–8. doi:10.1155/2020/1701326.
   Web of Science ®Google Scholar
• Yuan L, Zhang S, Li H, Yang F, Mushtaq N, Ullah S, Shi Y, An C, Xu J. The influence of gut microbiota dysbiosis to the efficacy of 5-fluorouracil treatment on colorectal cancer. Biomed Pharmacother. 2018;108:184–193. doi:10.1016/j.biopha.2018.08.165.
   PubMed Web of Science ®Google Scholar
• Roberti MP, Yonekura S, Duong CPM, Picard M, Ferrere G, Tidjani Alou M, Rauber C, Iebba V, Lehmann CHK, Amon L. et al. Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer. Nat Med. 2020;26(6):919–931. doi:10.1038/s41591-020-0882-8.
   PubMed Web of Science ®Google Scholar
• Fulop DJ, Zylberberg HM, Wu YL, Aronson A, Labiner AJ, Wisnivesky J, Cohen DJ, Sigel KM, Lucas AL. Association of antibiotic receipt with survival among patients with metastatic pancreatic ductal adenocarcinoma receiving chemotherapy. JAMA Netw Open. 2023;6(3):E234254. doi:10.1001/jamanetworkopen.2023.4254.
   PubMed Web of Science ®Google Scholar
• Imai H, Saijo K, Komine K, Otsuki Y, Ohuchi K, Sato Y, Okita A, Takahashi M, Takahashi S, Shirota H. et al. Antibiotic therapy augments the efficacy of gemcitabine-containing regimens for advanced cancer: a retrospective study. Cancer Manag Res. 2019;11:7953–7965. doi:10.2147/CMAR.S215.697.
   PubMed Web of Science ®Google Scholar
• Yue B, Gao R, Wang Z, Dou W. Microbiota-host-irinotecan axis: a new insight toward irinotecan chemotherapy. Front Cell Infect Microbiol. 2021;11:1–15. doi:10.3389/fcimb.2021.710945.
   Web of Science ®Google Scholar
• Wallace BD, Wang H, Lane KT, Scott JE, Orans J, Koo JS, Venkatesh M, Jobin C, Yeh L-A, Mani S. et al. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science. 2010;330(6005):831–835. doi:10.1126/science.1191175.
   PubMed Web of Science ®Google Scholar
• Lin HY, Chen C-Y, Lin T-C, Yeh L-F, Hsieh W-C, Gao S, Burnouf P-A, Chen B-M, Hsieh T-J, Dashnyam P. et al. Entropy-driven binding of gut bacterial β-glucuronidase inhibitors ameliorates irinotecan-induced toxicity. Commun Biol. 2021;4(1):1–10. doi:10.1038/s42003-021-01815-w.
   PubMed Web of Science ®Google Scholar
• Pedroso SHSP, Vieira AT, Bastos RW, Oliveira JS, Cartelle CT, Arantes RME, Soares PMG, Generoso SV, Cardoso VN, Teixeira MM. et al. Evaluation of mucositis induced by irinotecan after microbial colonization in germ-free mice. Microbiology. 2015;161(10):1950–1960. doi:10.1099/mic.0.000149.
   PubMedGoogle Scholar
• Kehrer DFS, Sparreboom A, Verweij J, de Bruijn P, Nierop CA, van de Schraaf J, Ruijgrok EJ, de Jonge MJ. Advances in brief modulation of irinotecan-induced diarrhea by cotreatment with neomycin in cancer patients. Clin Cancer Res. 2001;7:1136–1141.
   PubMed Web of Science ®Google Scholar
• de Jong FA, Kehrer DFS, Mathijssen RHJ, Creemers G-J, de Bruijn P, van Schaik RHN, Planting AST, van der Gaast A, Eskens FALM, Janssen JTP. et al. Prophylaxis of irinotecan-induced diarrhea with neomycin and potential role for UGT1A1*28 genotype screening: a double-blind, randomized, placebo-controlled study. Oncologist. 2006;11(8):944–954. doi:10.1634/theoncologist.11-8-944.
   PubMed Web of Science ®Google Scholar
• Sharma R, Tobin P, Clarke SJ. Management of chemotherapy-induced nausea, vomiting, oral mucositis, and diarrhoea. Lancet Oncol. 2005;6(2):93–102. doi:10.1016/S1470-2045(05)01735-3.
   PubMed Web of Science ®Google Scholar
• Makihara K, Nakamura S, Miyagi K, Ueno H, Nakata I. Clarithromycin co-administration does not increase irinotecan (CPT-11) toxicity in colorectal cancer patients. Cancer Chemother Pharmacol. 2017;80(3):527–533. doi:10.1007/s00280-017-3388-4.
   PubMed Web of Science ®Google Scholar
• Kurita A, Kado S, Matsumoto T, Asakawa N, Kaneda N, Kato I, Uchida K, Onoue M, Yokokura T. Streptomycin alleviates irinotecan-induced delayed-onset diarrhea in rats by a mechanism other than inhibition of β-glucuronidase activity in intestinal lumen. Cancer Chemother Pharmacol. 2011;67(1):201–213. doi:10.1007/s00280-010-1310-4.
   PubMed Web of Science ®Google Scholar
• Lo EKK, Leung HKM, Zhang F, El-Nezami H. Gut microbiota: Impact on 5-fluorouracil efficacy and toxicity. Curr Opin Toxicol. 2023;36:100423. doi:10.1016/j.cotox.2023.100423.
   Web of Science ®Google Scholar
• Shen S, Lim G, You Z, Ding W, Huang P, Ran C, Doheny J, Caravan P, Tate S, Hu K. et al. Gut microbiota is critical for the induction of chemotherapy-induced pain. Nat Neurosci. 2017;20(9):1213–1216. doi:10.1038/nn.4606.
   PubMed Web of Science ®Google Scholar
• Panebianco C, Adamberg K, Jaagura M, Copetti M, Fontana A, Adamberg S, Kolk K, Vilu R, Andriulli A, Pazienza V. et al. Influence of gemcitabine chemotherapy on the microbiota of pancreatic cancer xenografted mice. Cancer Chemother Pharmacol. 2018;81(4):773–782. doi:10.1007/s00280-018-3549-0.
   PubMed Web of Science ®Google Scholar
• Hamouda N, Sano T, Oikawa Y, Ozaki T, Shimakawa M, Matsumoto K, Amagase K, Higuchi K, Kato S. Apoptosis, dysbiosis and expression of inflammatory cytokines are sequential events in the development of 5-fluorouracil-induced intestinal mucositis in mice. Basic Clin Pharmacol Toxicol. 2017;121(3):159–168. doi:10.1111/bcpt.12793.
   PubMed Web of Science ®Google Scholar
• Goel N, Nadler A, Reddy S, Hoffman JP, Pitt HA. Biliary microbiome in pancreatic cancer: alterations with neoadjuvant therapy. Hpb. 2019;21(12):1753–1760. doi:10.1016/j.hpb.2019.04.005.
   PubMed Web of Science ®Google Scholar
• Nadeem SO, Jajja MR, Maxwell DW, Pouch SM, Sarmiento JM. Neoadjuvant chemotherapy for pancreatic cancer and changes in the biliary microbiome. Am J Surg. 2021;222(1):3–7. doi:10.1016/j.amjsurg.2020.09.042.
   PubMed Web of Science ®Google Scholar
• Balachandran VP, Łuksza M, Zhao JN, Makarov V, Moral JA, Remark R, Herbst B, Askan G, Bhanot U, Senbabaoglu Y. et al. Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature. 2017;551(7681):S512–S516. doi:10.1038/nature24462.
   PubMed Web of Science ®Google Scholar
• Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N, Flament C, Rusakiewicz S, Routy B, Roberti MP, Duong CPM. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350(6264):1079–1084. doi:10.1126/science.aad1329.
   PubMed Web of Science ®Google Scholar
• Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, Benyamin FW, Man Lei Y, Jabri B, Alegre M-L. et al. Commensal bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy. Science. 2015;350(6264):1084–1089. doi:10.1126/science.aac4255.
   PubMed Web of Science ®Google Scholar
• Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP. et al. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science. 2018;359(6371):91–97. doi:10.1126/science.aan3706.
   PubMed Web of Science ®Google Scholar
• Si W, Liang H, Bugno J, Xu Q, Ding X, Yang K, Fu Y, Weichselbaum RR, Zhao X, Wang L. et al. Lactobacillus rhamnosus GG induces cGAS/STING- dependent type i interferon and improves response to immune checkpoint blockade. Gut. 2022;71(3):521–533. doi:10.1136/gutjnl-2020-323426.
   PubMed Web of Science ®Google Scholar
• Tanoue T, Morita S, Plichta DR, Skelly AN, Suda W, Sugiura Y, Narushima S, Vlamakis H, Motoo I, Sugita K. et al. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature. 2019;565(7741):600–605. doi:10.1038/s41586-019-0878-z.
   PubMed Web of Science ®Google Scholar
• Davar D, Dzutsev AK, McCulloch JA, Rodrigues RR, Chauvin J-M, Morrison RM, Deblasio RN, Menna C, Ding Q, Pagliano O. et al. Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients. Science. 2021;371(6529):595–602. doi:10.1126/science.abf3363.
   PubMed Web of Science ®Google Scholar
• Baruch EN, Youngster I, Ben-Betzalel G, Ortenberg R, Lahat A, Katz L, Adler K, Dick-Necula D, Raskin S, Bloch N. et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science. 2021;371(6529):602–609. doi:10.1126/science.abb5920.
   PubMed Web of Science ®Google Scholar
• Postler TS, Ghosh S. Understanding the holobiont: how microbial metabolites affect human health and shape the immune system. Cell Metab. 2017;26(1):110–130. doi:10.1016/j.cmet.2017.05.008.
   PubMed Web of Science ®Google Scholar
• Natoni F, Diolordi L, Santoni C, Gilardini Montani MS. Sodium butyrate sensitises human pancreatic cancer cells to both the intrinsic and the extrinsic apoptotic pathways. Biochim Biophys Acta - Mol Cell Res. 2005;1745(3):318–329. doi:10.1016/j.bbamcr.2005.07.003.
   Web of Science ®Google Scholar
• Bülow R, Fitzner B, Sparmann G, Emmrich J, Liebe S, Jaster R. Antifibrogenic effects of histone deacetylase inhibitors on pancreatic stellate cells. Biochem Pharmacol. 2007;74(12):1747–1757. doi:10.1016/j.bcp.2007.08.023.
   PubMed Web of Science ®Google Scholar
• Panebianco C, Villani A, Pisati F, Orsenigo F, Ulaszewska M, Latiano TP, Potenza A, Andolfo A, Terracciano F, Tripodo C. et al. Butyrate, a postbiotic of intestinal bacteria, affects pancreatic cancer and gemcitabine response in in vitro and in vivo models. Biomed Pharmacother. 2022;151:113163. doi:10.1016/j.biopha.2022.113163.
   PubMed Web of Science ®Google Scholar
• Shuwen H, Yangyanqiu W, Jian C, Boyang H, Gong C, Jing Z. Synergistic effect of sodium butyrate and oxaliplatin on colorectal cancer. Transl Oncol. 2023;27:101598. doi:10.1016/j.tranon.2022.101598.
   PubMed Web of Science ®Google Scholar
• Yue X, Wen S, Long-Kun D, Man Y, Chang S, Min Z, Shuang-Yu L, Xin Q, Jie M, Liang W. et al. Three important short-chain fatty acids (SCFAs) attenuate the inflammatory response induced by 5-FU and maintain the integrity of intestinal mucosal tight junction. BMC Immunol. 2022;23(1):1–13. doi:10.1186/s12865-022-00495-3.
   PubMed Web of Science ®Google Scholar
• Gao J, Xu K, Liu H, Liu G, Bai M, Peng C, Li T, Yin Y. Impact of the gut microbiota on intestinal immunity mediated by tryptophan metabolism. Front Cell Infect Microbiol. 2018;8:1–22. doi:10.3389/fcimb.2018.00013.
   PubMed Web of Science ®Google Scholar
• Hezaveh K, Shinde RS, Klötgen A, Halaby MJ, Lamorte S, Ciudad MT, Quevedo R, Neufeld L, Liu ZQ, Jin R. et al. Tryptophan-derived microbial metabolites activate the aryl hydrocarbon receptor in tumor-associated macrophages to suppress anti-tumor immunity. Immunity. 2022;55(2):324–340.e8. doi:10.1016/j.immuni.2022.01.006.
   PubMed Web of Science ®Google Scholar
• Collins SL, Stine JG, Bisanz JE, Okafor CD, Patterson AD. Bile acids and the gut microbiota: metabolic interactions and impacts on disease. Nat Rev Microbiol. 2023;21(4):236–247. doi:10.1038/s41579-022-00805-x.
   PubMed Web of Science ®Google Scholar
• Yang C, Yuan H, Gu J, Xu D, Wang M, Qiao J, Yang X, Zhang J, Yao M, Gu J. et al. ABCA8-mediated efflux of taurocholic acid contributes to gemcitabine insensitivity in human pancreatic cancer via the S1PR2-ERK pathway. Cell Death Discov. 2021;7(1). doi:10.1038/s41420-020-00390-z.
   Web of Science ®Google Scholar
• Gál E, Veréb Z, Kemény L, Rakk D, Szekeres A, Becskeházi E, Tiszlavicz L, Takács T, Czakó L, Hegyi P. et al. Bile accelerates carcinogenic processes in pancreatic ductal adenocarcinoma cells through the overexpression of MUC4. Sci Rep. 2020;10(1):1–16. doi:10.1038/s41598-020-79181-6.
   PubMed Web of Science ®Google Scholar
• Tucker ON, Dannenberg AJ, Yang EK, Fahey TJ. Bile acids induce cyclooxygenase-2 expression in human pancreatic cancer cell lines. Carcinogenesis. 2004;25(3):419–423. doi:10.1093/carcin/bgh010.
   PubMed Web of Science ®Google Scholar
• Nagathihalli NS, Beesetty Y, Lee W, Washington MK, Chen X, Lockhart AC, Merchant NB. Novel mechanistic insights into ectodomain shedding of egfr ligands amphiregulin and TGF-α: impact on gastrointestinal cancers driven by secondary bile acids. Cancer Res. 2014;74(7):2062–2072. doi:10.1158/0008-5472.CAN-13-2329.
   PubMed Web of Science ®Google Scholar
• Shrader HR, Miller AM, Tomanek-Chalkley A, McCarthy A, Coleman KL, Ear PH, Mangalam AK, Salem AK, Chan CHF. Effect of bacterial contamination in bile on pancreatic cancer cell survival. Surgery. 2021;169(3):617–622. doi:10.1016/j.surg.2020.09.029.
   PubMed Web of Science ®Google Scholar
• Mendez R, Kesh K, Arora N, Di Martino L, McAllister F, Merchant N, Banerjee S, Banerjee S. Microbial dysbiosis and polyamine metabolism as predictive markers for early detection of pancreatic cancer. Carcinogenesis. 2020;41(5):561–570. doi:10.1093/carcin/bgz116.
   PubMed Web of Science ®Google Scholar
• Nakkina SP, Gitto SB, Pandey V, Parikh JG, Geerts D, Maurer HC, Olive KP, Phanstiel O, Altomare DA. Differential expression of polyamine pathways in human pancreatic tumor progression and effects of polyamine blockade on tumor microenvironment. Cancers. 2021;13(24):6391. doi:10.3390/cancers13246391.
   PubMed Web of Science ®Google Scholar
• Lee M, Dennis C, Naqvi I, Dailey L, Lorzadeh A, Ye G, Zaytouni T, Adler A, Hitchcock DS, Lin L. et al. Ornithine aminotransferase supports polyamine synthesis in pancreatic cancer. Nature. 2023;616(7956):339–347. doi:10.1038/s41586-023-05891-2.
   PubMed Web of Science ®Google Scholar
• Tofalo R, Cocchi S, Suzzi G. Polyamines and gut microbiota. Front Nutr. 2019;6:1–5. doi:10.3389/fnut.2019.00016.
   PubMed Web of Science ®Google Scholar
• Yin J, Ren W, Huang X, Deng J, Li T, Yin Y. Potential mechanisms connecting purine metabolism and cancer therapy. Front Immunol. 2018;9:1–8. doi:10.3389/fimmu.2018.01697.
   PubMed Web of Science ®Google Scholar
• Santana-Codina N, Roeth AA, Zhang Y, Yang A, Mashadova O, Asara JM, Wang X, Bronson RT, Lyssiotis CA, Ying H. et al. Oncogenic KRAS supports pancreatic cancer through regulation of nucleotide synthesis. Nat Commun. 2018;9(1):4945. doi:10.1038/s41467-018-07472-8.
   PubMedGoogle Scholar
• Lee JS, Wang RX, Goldberg MS, Clifford GP, Kao DJ, Colgan SP. Microbiota-sourced purines support wound healing and mucous barrier function. iScience. 2020;23(6):101226. doi:10.1016/j.isci.2020.101226.
   PubMed Web of Science ®Google Scholar
• Mager LF, Burkhard R, Pett N, Cooke NCA, Brown K, Ramay H, Paik S, Stagg J, Groves RA, Gallo M. et al. Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy. Science. 2020;369(6510):1481–1489. doi:10.1126/science.abc3421.
   PubMed Web of Science ®Google Scholar
• Capurso G, Sette C. Drug resistance in pancreatic cancer: new player caught in act. EBioMedicine. 2019;40:39–40. doi:10.1016/j.ebiom.2019.02.008.
   PubMed Web of Science ®Google Scholar
• Plagemann CN, Hidalgo M, Garrido-Laguna I. From state- of-the- art treatments to novel therapies for advanced-stage pancreatic cancer. Nat Rev Clin Oncol. 2020;17(2):108–123. doi:10.1038/s41571-019-0281-6.
   PubMed Web of Science ®Google Scholar
• Zmora N, Suez J, Elinav E. You are what you eat: diet, health and the gut microbiota. Nat Rev Gastroenterol Hepatol. 2019;16(1):35–56. doi:10.1038/s41575-018-0061-2.
   PubMed Web of Science ®Google Scholar
• Yang J, Wei H, Zhou Y, Szeto C-H, Li C, Lin Y, Coker OO, Lau HCH, Chan AWH, Sung JJY. et al. High-fat diet promotes colorectal tumorigenesis through modulating gut microbiota and metabolites. Gastroenterology. 2022;162(1):135–149.e2. doi:10.1053/j.gastro.2021.08.041.
   PubMed Web of Science ®Google Scholar
• Bultman SJ. Molecular pathways: gene–environment interactions regulating dietary fiber induction of proliferation and apoptosis via butyrate for cancer prevention. Clin Cancer Res. 2014;20(4):799–803. doi:10.1158/1078-0432.CCR-13-2483.
   PubMed Web of Science ®Google Scholar
• Mao QQ, Lin Y-W, Chen H, Qin J, Zheng X-Y, Xu X, Xie L-P. Dietary fiber intake is inversely associated with risk of pancreatic cancer: a meta-analysis. Asia Pac J Clin Nutr. 2017;26(1):89–96. doi:10.6133/apjcn.102015.03.
   PubMed Web of Science ®Google Scholar
• Panebianco C, Adamberg K, Adamberg S, Saracino C, Jaagura M, Kolk K, Di Chio A, Graziano P, Vilu R, Pazienza V. et al. Engineered resistant-starch (ERS) diet shapes colon microbiota profile in parallel with the retardation of tumor growth in in vitro and in vivo pancreatic cancer models. Nutrients. 2017;9(4):331. doi:10.3390/nu9040331.
   PubMed Web of Science ®Google Scholar
• D’Aronzo M, Vinciguerra M, Mazza T, Panebianco C, Saracino C, Pereira SP, Graziano P, Pazienza V. Fasting cycles potentiate the efficacy of gemcitabine treatment in in vitro and in vivo pancreatic cancer models. Oncotarget. 2015;6(21):18545–18557. doi:10.18632/oncotarget.4186.
   PubMedGoogle Scholar
• Lin XB, Farhangfar A, Valcheva R, Sawyer MB, Dieleman L, Schieber A, Gänzle MG, Baracos V. The role of intestinal microbiota in development of irinotecan toxicity and in toxicity reduction through dietary fibres in rats. PloS One. 2014;9(1):e83644. doi:10.1371/journal.pone.0083644.
   PubMed Web of Science ®Google Scholar
• Mirmiran P, Bahadoran Z, Gaeini Z. Common limitations and challenges of dietary clinical trials for translation into clinical practices. Int J Endocrinol Metab. 2021;19(3):1–9. doi:10.5812/ijem.108170.
   Web of Science ®Google Scholar
• Fu X, Liu Z, Zhu C, Mou H, Kong Q. Nondigestible carbohydrates, butyrate, and butyrate-producing bacteria. Crit Rev Food Sci Nutr. 2019;59(sup1):S130–S152. doi:10.1080/10408398.2018.1542587.
   PubMed Web of Science ®Google Scholar
• Panebianco C, Pisati F, Ulaszewska M, Andolfo A, Villani A, Federici F, Laura M, Rizzi E, Potenza A, Latiano TP. et al. Tuning gut microbiota through a probiotic blend in gemcitabine‐treated pancreatic cancer xenografted mice. Clin Transl Med. 2021;11(11):1–7. doi:10.1002/ctm2.580.
   PubMed Web of Science ®Google Scholar
• Prajapati N, Patel J, Singh S, Yadav VK, Joshi C, Patani A, Prajapati D, Sahoo DK, Patel A. Postbiotic production: harnessing the power of microbial metabolites for health applications. Front Microbiol. 2023;14:1–16. doi:10.3389/fmicb.2023.1306192.
   Web of Science ®Google Scholar
• Chrysostomou D, Roberts LA, Marchesi JR, Kinross JM. Gut microbiota modulation of efficacy and toxicity of cancer chemotherapy and immunotherapy. Gastroenterology. 2023;164(2):198–213. doi:10.1053/j.gastro.2022.10.018.
   PubMed Web of Science ®Google Scholar
• Mohindroo C, Hasanov M, Rogers JE, Dong W, Prakash LR, Baydogan S, Mizrahi JD, Overman MJ, Varadhachary GR, Wolff RA. et al. Antibiotic use influences outcomes in advanced pancreatic adenocarcinoma patients. Cancer Med. 2021;10(15):5041–5050. doi:10.1002/cam4.3870.
   PubMed Web of Science ®Google Scholar
• Hwang YJ, Myung H. Engineered bacteriophage T7 as a potent anticancer agent in vivo. Front Microbiol. 2020;11:491001. doi:10.3389/fmicb.2020.491001.
   PubMed Web of Science ®Google Scholar
• Kabwe M, Dashper S, Tucci J. The microbiome in pancreatic cancer-implications for diagnosis and precision bacteriophage therapy for this low survival disease. Front Cell Infect Microbiol. 2022;12:1–14. doi:10.3389/fcimb.2022.871293.
   Web of Science ®Google Scholar
• Identifier: NCT04975217. Fecal microbial transplants for the treatment of pancreatic cancer. US National Library Of Medicine. (Accessed: 20th October 2023). https://classic.clinicaltrials.gov/ct2/show/NCT04975217
   Google Scholar