Abstract
Cancer develops in multicellular organisms from cells that ignore the rules of cooperation and escape the mechanisms of anti-cancer surveillance. Tumorigenesis is jointly encountered by the host and microbiota, a vast collection of microorganisms that live on the external and internal epithelial surfaces of the body. The largest community of human microbiota resides in the gastrointestinal tract where commensal, symbiotic and pathogenic microorganisms interact with the intestinal barrier and gut mucosal lymphoid tissue, creating a tumor microenvironment in which cancer cells thrive or perish. Aberrant composition and function of the gut microbiota (dysbiosis) has been associated with tumorigenesis by inducing inflammation, promoting cell growth and proliferation, weakening immunosurveillance, and altering food and drug metabolism or other biochemical functions of the host. However, recent research has also identified several mechanisms through which gut microbiota support the host in the fight against cancer. These mechanisms include the use of antigenic mimicry, biotransformation of chemotherapeutic agents, and other mechanisms to boost anti-cancer immune responses and improve the efficacy of cancer immunotherapy. Further research in this rapidly advancing field is expected to identify additional microbial metabolites with tumor suppressing properties, map the complex interactions of host-microbe ‘transkingdom network’ with cancer cells, and elucidate cellular and molecular pathways underlying the impact of specific intestinal microbial configurations on immune checkpoint inhibitor therapy.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aktipis CA, Nesse RM (2013) Evolutionary foundations for cancer biology. Evol Appl 6:144–159. https://doi.org/10.1111/eva.12034
Aktipis CA, Boddy AM, Jansen G, Hibner U, Hochberg ME, Maley CC, Wilkinson GS (2015) Cancer across the tree of life: cooperation and cheating in multicellularity. Philos Trans R Soc Lond B Biol Sci 370:pii: 20140219. https://doi.org/10.1098/rstb.2014.0219
Ang Z, Ding JL (2016) GPR41 and GPR43 in obesity and inflammation – protective or causative? Front Immunol 7:28. https://doi.org/10.3389/fimmu.2016.00028
Arkan MC (2017) The intricate connection between diet, microbiota, and cancer: a jigsaw puzzle. Semin Immunol 32:35–42. https://doi.org/10.1016/j.smim.2017.08.009
Arumugam M et al (2011) Enterotypes of the human gut microbiome. Nature 473:174–180. https://doi.org/10.1038/nature09944
Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI (2005) Host-bacterial mutualism in the human intestine. Science 307:1915–1920. https://doi.org/10.1126/science.1104816
Balachandran VP et al (2017) Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature 551:512–516. https://doi.org/10.1038/nature24462
Bhatt AP, Redinbo MR, Bultman SJ (2017) The role of the microbiome in cancer development and therapy. CA Cancer J Clin 67:326–344. https://doi.org/10.3322/caac.21398
Bouziat R, Jabri B (2015) Breaching the gut-vascular barrier. Science 350:742–743. https://doi.org/10.1126/science.aad6768
Brand K (1997) Aerobic glycolysis by proliferating cells: protection against oxidative stress at the expense of energy yield. J Bioenerg Biomembr 29:355–364
Buc E et al (2013) High prevalence of mucosa-associated E. coli producing cyclomodulin and genotoxin in colon cancer. PLoS One 8:e56964. https://doi.org/10.1371/journal.pone.0056964
Bultman SJ (2016) The microbiome and its potential as a cancer preventive intervention. Semin Oncol 43:97–106. https://doi.org/10.1053/j.seminoncol.2015.09.001
Chen H, Lin F, Xing K, He X (2015) The reverse evolution from multicellularity to unicellularity during carcinogenesis. Nat Commun 6:6367. https://doi.org/10.1038/ncomms7367
Comstock LE, Coyne MJ (2003) Bacteroides thetaiotaomicron: a dynamic, niche-adapted human symbiont. Bioessays 25:926–929. https://doi.org/10.1002/bies.10350
Costerton JW, Stewart PS, Greenberg EP (1999) Bacterial biofilms: a common cause of persistent infections. Science 284:1318–1322
Coyte KZ, Schluter J, Foster KR (2015) The ecology of the microbiome: networks, competition, and stability. Science 350:663–666. https://doi.org/10.1126/science.aad2602
de Martel C, Ferlay J, Franceschi S, Vignat J, Bray F, Forman D, Plummer M (2012) Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol 13:607–615. https://doi.org/10.1016/S1470-2045(12)70137-7
DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7:11–20. https://doi.org/10.1016/j.cmet.2007.10.002
Dejea CM et al (2014) Microbiota organization is a distinct feature of proximal colorectal cancers. Proc Natl Acad Sci U S A 111:18321–18326. https://doi.org/10.1073/pnas.1406199111
Devkota S et al (2012) Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice. Nature 487:104–108. https://doi.org/10.1038/nature11225
Donia MS, Fischbach MA (2015) Small molecules from the human microbiota. Science 349:1254766. https://doi.org/10.1126/science.1254766
Donohoe DR, Collins LB, Wali A, Bigler R, Sun W, Bultman SJ (2012) The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol Cell 48:612–626. https://doi.org/10.1016/j.molcel.2012.08.033
Drewes JL, Housseau F, Sears CL (2016) Sporadic colorectal cancer: microbial contributors to disease prevention, development and therapy. Br J Cancer 115:273–280. https://doi.org/10.1038/bjc.2016.189
Dupont A, Heinbockel L, Brandenburg K, Hornef MW (2014) Antimicrobial peptides and the enteric mucus layer act in concert to protect the intestinal mucosa. Gut Microbes 5:761–765. https://doi.org/10.4161/19490976.2014.972238
Dutta U, Garg PK, Kumar R, Tandon RK (2000) Typhoid carriers among patients with gallstones are at increased risk for carcinoma of the gallbladder. Am J Gastroenterol 95:784–787. https://doi.org/10.1111/j.1572-0241.2000.01860.x
Everard A et al (2013) Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A 110:9066–9071. https://doi.org/10.1073/pnas.1219451110
Fais T, Delmas J, Barnich N, Bonnet R, Dalmasso G (2018) Colibactin: more than a new bacterial toxin. Toxins (Basel) 10:pii: E151. https://doi.org/10.3390/toxins10040151
Fallarino F et al (2006) The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol 176:6752–6761
Fan CA, Reader J, Roque DM (2018) Review of immune therapies targeting ovarian cancer. Curr Treat Options Oncol 19:74. https://doi.org/10.1007/s11864-018-0584-3
Fischbach MA, Sonnenburg JL (2011) Eating for two: how metabolism establishes interspecies interactions in the gut. Cell Host Microbe 10:336–347. https://doi.org/10.1016/j.chom.2011.10.002
Foster KR, Schluter J, Coyte KZ, Rakoff-Nahoum S (2017) The evolution of the host microbiome as an ecosystem on a leash. Nature 548:43–51. https://doi.org/10.1038/nature23292
Fulbright LE, Ellermann M, Arthur JC (2017) The microbiome and the hallmarks of cancer. PLoS Pathog 13:e1006480. https://doi.org/10.1371/journal.ppat.1006480
Galloway-Pena JR, Jenq RR, Shelburne SA (2017) Can consideration of the microbiome improve antimicrobial utilization and treatment outcomes in the oncology patient? Clin Cancer Res 23:3263–3268. https://doi.org/10.1158/1078-0432.CCR-16-3173
Gao J et al (2018) Impact of the gut microbiota on intestinal immunity mediated by tryptophan metabolism. Front Cell Infect Microbiol 8:13. https://doi.org/10.3389/fcimb.2018.00013
Garrett WS (2015) Cancer and the microbiota. Science 348:80–86. https://doi.org/10.1126/science.aaa4972
Garrett WS, Gordon JI, Glimcher LH (2010) Homeostasis and inflammation in the intestine. Cell 140:859–870. https://doi.org/10.1016/j.cell.2010.01.023
Giannelli V, Di Gregorio V, Iebba V, Giusto M, Schippa S, Merli M, Thalheimer U (2014) Microbiota and the gut-liver axis: bacterial translocation, inflammation and infection in cirrhosis. World J Gastroenterol 20:16795–16810. https://doi.org/10.3748/wjg.v20.i45.16795
Gopalakrishnan V, Helmink BA, Spencer CN, Reuben A, Wargo JA (2018a) The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy. Cancer Cell 33:570–580. https://doi.org/10.1016/j.ccell.2018.03.015
Gopalakrishnan V et al (2018b) Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 359:97–103. https://doi.org/10.1126/science.aan4236
Goto Y, Kiyono H (2012) Epithelial barrier: an interface for the cross-communication between gut flora and immune system. Immunol Rev 245:147–163. https://doi.org/10.1111/j.1600-065X.2011.01078.x
Greer R, Dong X, Morgun A, Shulzhenko N (2016) Investigating a holobiont: microbiota perturbations and transkingdom networks. Gut Microbes 7:126–135. https://doi.org/10.1080/19490976.2015.1128625
Grohmann U, Fallarino F, Puccetti P (2003) Tolerance, DCs and tryptophan: much ado about IDO. Trends Immunol 24:242–248
Gur C et al (2015) Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity 42:344–355. https://doi.org/10.1016/j.immuni.2015.01.010
Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674. https://doi.org/10.1016/j.cell.2011.02.013
Hernandez P, Gronke K, Diefenbach A (2018) A catch-22: Interleukin-22 and cancer. Eur J Immunol 48:15–31. https://doi.org/10.1002/eji.201747183
Hsu PP, Sabatini DM (2008) Cancer cell metabolism: Warburg and beyond. Cell 134:703–707. https://doi.org/10.1016/j.cell.2008.08.021
Huitzil S, Sandoval-Motta S, Frank A, Aldana M (2018) Modeling the role of the microbiome in evolution. Front Physiol 9:1836. https://doi.org/10.3389/fphys.2018.01836
Human Microbiome Project C (2012) Structure, function and diversity of the healthy human microbiome. Nature 486:207–214. https://doi.org/10.1038/nature11234
Iida N et al (2013) Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342:967–970. https://doi.org/10.1126/science.1240527
Johnson CH et al (2015) Metabolism links bacterial biofilms and colon carcinogenesis. Cell Metab 21:891–897. https://doi.org/10.1016/j.cmet.2015.04.011
Joice R, Yasuda K, Shafquat A, Morgan XC, Huttenhower C (2014) Determining microbial products and identifying molecular targets in the human microbiome. Cell Metab 20:731–741. https://doi.org/10.1016/j.cmet.2014.10.003
Kroemer G, Zitvogel L (2018) Cancer immunotherapy in 2017: the breakthrough of the microbiota. Nat Rev Immunol 18:87–88. https://doi.org/10.1038/nri.2018.4
Kudo M (2018) Systemic therapy for hepatocellular carcinoma: latest advances. Cancers (Basel) 10. https://doi.org/10.3390/cancers10110412
Le Chatelier E et al (2013) Richness of human gut microbiome correlates with metabolic markers. Nature 500:541–546. https://doi.org/10.1038/nature12506
Lee WJ, Hase K (2014) Gut microbiota-generated metabolites in animal health and disease. Nat Chem Biol 10:416–424. https://doi.org/10.1038/nchembio.1535
Leong SP, Aktipis A, Maley C (2018) Cancer initiation and progression within the cancer microenvironment. Clin Exp Metastasis 35:361–367. https://doi.org/10.1007/s10585-018-9921-y
Llorente C, Schnabl B (2015) The gut microbiota and liver disease. Cell Mol Gastroenterol Hepatol 1:275–284. https://doi.org/10.1016/j.jcmgh.2015.04.003
Long SL, Gahan CGM, Joyce SA (2017) Interactions between gut bacteria and bile in health and disease. Mol Aspects Med 56:54–65. https://doi.org/10.1016/j.mam.2017.06.002
Lu R, Bosland M, Xia Y, Zhang YG, Kato I, Sun J (2017) Presence of Salmonella AvrA in colorectal tumor and its precursor lesions in mouse intestine and human specimens. Oncotarget 8:55104–55115. https://doi.org/10.18632/oncotarget.19052
Marchiando AM, Graham WV, Turner JR (2010) Epithelial barriers in homeostasis and disease. Annu Rev Pathol 5:119–144. https://doi.org/10.1146/annurev.pathol.4.110807.092135
Martin FP et al (2007) A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model. Mol Syst Biol 3:112. https://doi.org/10.1038/msb4100153
Matson V et al (2018) The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 359:104–108. https://doi.org/10.1126/science.aao3290
Maynard Smith J (1998) The units of selection. Novartis Found Symp 213:203–211. discussion 211–207
Maynard Smith J, Szathmáry E (1995) The major transitions in evolution. W.H. Freeman Spektrum, Oxford/New York
Morgillo F et al (2018) Carcinogenesis as a result of multiple inflammatory and oxidative hits: a comprehensive review from tumor microenvironment to gut microbiota. Neoplasia 20:721–733. https://doi.org/10.1016/j.neo.2018.05.002
Muller EEL, Faust K, Widder S, Herold M, Martinez Abbas S, Wilmes P (2018) Using metabolic networks to resolve ecological properties of microbiomes. Curr Opin Syst Biol 8:73–80
Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S (2012) Host-gut microbiota metabolic interactions. Science 336:1262–1267. https://doi.org/10.1126/science.1223813
Noonan DM, De Lerma Barbaro A, Vannini N, Mortara L, Albini A (2008) Inflammation, inflammatory cells and angiogenesis: decisions and indecisions. Cancer Metastasis Rev 27:31–40. https://doi.org/10.1007/s10555-007-9108-5
Pardoll D (2015) Cancer and the immune system: basic concepts and targets for intervention. Semin Oncol 42:523–538. https://doi.org/10.1053/j.seminoncol.2015.05.003
Pavlova NN, Thompson CB (2016) The emerging hallmarks of cancer metabolism. Cell Metab 23:27–47. https://doi.org/10.1016/j.cmet.2015.12.006
Perez-Chanona E, Trinchieri G (2016) The role of microbiota in cancer therapy. Curr Opin Immunol 39:75–81. https://doi.org/10.1016/j.coi.2016.01.003
Pfeiffer T, Schuster S, Bonhoeffer S (2001) Cooperation and competition in the evolution of ATP-producing pathways. Science 292:504–507. https://doi.org/10.1126/science.1058079
Plichta DR et al (2016) Transcriptional interactions suggest niche segregation among microorganisms in the human gut. Nat Microbiol 1:16152. https://doi.org/10.1038/nmicrobiol.2016.152
Pope JL, Tomkovich S, Yang Y, Jobin C (2017) Microbiota as a mediator of cancer progression and therapy. Transl Res 179:139–154. https://doi.org/10.1016/j.trsl.2016.07.021
Quail DF, Joyce JA (2013) Microenvironmental regulation of tumor progression and metastasis. Nat Med 19:1423–1437. https://doi.org/10.1038/nm.3394
Quante M, Varga J, Wang TC, Greten FR (2013) The gastrointestinal tumor microenvironment. Gastroenterology 145:63–78. https://doi.org/10.1053/j.gastro.2013.03.052
Restifo NP, Dudley ME, Rosenberg SA (2012) Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol 12:269–281. https://doi.org/10.1038/nri3191
Reticker-Flynn NE, Engleman EG (2019) A gut punch fights cancer and infection. Nature 565:573–574. https://doi.org/10.1038/d41586-019-00133-w
Riscuta G, Xi D, Pierre-Victor D, Starke-Reed P, Khalsa J, Duffy L (2018) Diet, microbiome, and epigenetic changes in cancer. In: Dumitrescu RG, Verma M (eds) Cancer epigenetics for precision medicine. Methods in molecular biology. Humana Press, Clifton, pp 141–156
Robert C et al (2015) Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 372:2521–2532. https://doi.org/10.1056/NEJMoa1503093
Routy B et al (2018) Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359:91–97. https://doi.org/10.1126/science.aan3706
Rubinstein MR, Wang X, Liu W, Hao Y, Cai G, Han YW (2013) Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/beta-catenin signaling via its FadA adhesin. Cell Host Microbe 14:195–206. https://doi.org/10.1016/j.chom.2013.07.012
Schwabe RF, Jobin C (2013) The microbiome and cancer. Nat Rev Cancer 13:800–812. https://doi.org/10.1038/nrc3610
Sears CL (2009) Enterotoxigenic Bacteroides fragilis: a rogue among symbiotes. Clin Microbiol Rev 22:349–369. https://doi.org/10.1128/CMR.00053-08
Serpa J et al (2010) Butyrate-rich colonic microenvironment is a relevant selection factor for metabolically adapted tumor cells. J Biol Chem 285:39211–39223. https://doi.org/10.1074/jbc.M110.156026
Singh SB, Lin HC (2015) Hydrogen sulfide in physiology and diseases of the digestive tract. Microorganisms 3:866–889. https://doi.org/10.3390/microorganisms3040866
Sivan A et al (2015) Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350:1084–1089. https://doi.org/10.1126/science.aac4255
Sommer F, Backhed F (2013) The gut microbiota – masters of host development and physiology. Nat Rev Microbiol 11:227–238. https://doi.org/10.1038/nrmicro2974
Steinman RM (2007) Lasker basic medical research award. Dendritic cells: versatile controllers of the immune system. Nat Med 13:1155–1159. https://doi.org/10.1038/nm1643
Sun L, Suo C, Li ST, Zhang H, Gao P (2018) Metabolic reprogramming for cancer cells and their microenvironment: beyond the Warburg effect. Biochim Biophys Acta Rev Cancer 1870:51–66. https://doi.org/10.1016/j.bbcan.2018.06.005
Swartz MA et al (2012) Tumor microenvironment complexity: emerging roles in cancer therapy. Cancer Res 72:2473–2480. https://doi.org/10.1158/0008-5472.CAN-12-0122
Swidsinski A et al (2007) Comparative study of the intestinal mucus barrier in normal and inflamed colon. Gut 56:343–350. https://doi.org/10.1136/gut.2006.098160
Tanoue T et al (2019) A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature 565:600–605. https://doi.org/10.1038/s41586-019-0878-z
Thorburn AN, Macia L, Mackay CR (2014) Diet, metabolites, and “western-lifestyle” inflammatory diseases. Immunity 40:833–842. https://doi.org/10.1016/j.immuni.2014.05.014
Vetizou M et al (2015) Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350:1079–1084. https://doi.org/10.1126/science.aad1329
Wahlstrom A, Sayin SI, Marschall HU, Backhed F (2016) Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab 24:41–50. https://doi.org/10.1016/j.cmet.2016.05.005
Wallace BD et al (2010) Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 330:831–835. https://doi.org/10.1126/science.1191175
Wang R (2012) Physiological implications of hydrogen sulfide: a whiff exploration that blossomed. Physiol Rev 92:791–896. https://doi.org/10.1152/physrev.00017.2011
Warburg O, Poesener K, Negelein E (1924) Über den Stoffwechsel der Carcinomzelle. Biochem Z 152:309–344
Wasielewski H, Alcock J, Aktipis A (2016) Resource conflict and cooperation between human host and gut microbiota: implications for nutrition and health. Ann N Y Acad Sci 1372:20–28. https://doi.org/10.1111/nyas.13118
Wegiel B, Vuerich M, Daneshmandi S, Seth P (2018) Metabolic switch in the tumor microenvironment determines immune responses to anti-cancer therapy. Front Oncol 8:284. https://doi.org/10.3389/fonc.2018.00284
Wilson HL, Obradovic MR (2015) Evidence for a common mucosal immune system in the pig. Mol Immunol 66:22–34. https://doi.org/10.1016/j.molimm.2014.09.004
Wu S et al (2009) A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med 15:1016–1022. https://doi.org/10.1038/nm.2015
Wu C et al (2018) Forward genetic dissection of biofilm development by fusobacterium nucleatum: novel functions of cell division proteins FtsX and EnvC. MBio 9. https://doi.org/10.1128/mBio.00360-18
Yang T, Owen JL, Lightfoot YL, Kladde MP, Mohamadzadeh M (2013) Microbiota impact on the epigenetic regulation of colorectal cancer. Trends Mol Med 19:714–725. https://doi.org/10.1016/j.molmed.2013.08.005
Yoshimoto S et al (2013) Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499:97–101. https://doi.org/10.1038/nature12347
Yu T et al (2017) Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell 170:548–563.e516. https://doi.org/10.1016/j.cell.2017.07.008
Zelante T et al (2013) Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 39:372–385. https://doi.org/10.1016/j.immuni.2013.08.003
Zhou Z, Chen J, Yao H, Hu H (2018) Fusobacterium and colorectal cancer. Front Oncol 8:371. https://doi.org/10.3389/fonc.2018.00371
Zitvogel L, Galluzzi L, Viaud S, Vetizou M, Daillere R, Merad M, Kroemer G (2015) Cancer and the gut microbiota: an unexpected link. Sci Transl Med 7:271ps271. https://doi.org/10.1126/scitranslmed.3010473
Zitvogel L, Ayyoub M, Routy B, Kroemer G (2016) Microbiome and anticancer immunosurveillance. Cell 165:276–287. https://doi.org/10.1016/j.cell.2016.03.001
Zmora N, Suez J, Elinav E (2019) You are what you eat: diet, health and the gut microbiota. Nat Rev Gastroenterol Hepatol 16:35–56. https://doi.org/10.1038/s41575-018-0061-2
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Baffy, G. (2020). Gut Microbiota and Cancer of the Host: Colliding Interests. In: Serpa, J. (eds) Tumor Microenvironment . Advances in Experimental Medicine and Biology, vol 1219. Springer, Cham. https://doi.org/10.1007/978-3-030-34025-4_5
Download citation
DOI: https://doi.org/10.1007/978-3-030-34025-4_5
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-34024-7
Online ISBN: 978-3-030-34025-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)