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Epidemiology and Population Health

Spot-light on microbiota in obesity and cancer

International Journal of Obesity volume 45, pages 2291–2299 (2021)Cite this article

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Abstract

Over the last few years, the complexity and diversity of gut microbiota within and across individuals has been detailed in relation to human health. Further, understanding of the bidirectional association between gut microbiota and metabolic disorders has highlighted a complimentary, yet crucial role for microbiota in the onset and progression of obesity-related cancers. While strategies for cancer prevention and cure are known to work efficiently when supported by healthy diet and lifestyle choices and physical activity, emerging evidence suggests that the complex interplay relating microbiota both to neoplastic and metabolic diseases could aid strategies for cancer treatment and outcomes. This review will explore the experimental and clinical grounds supporting the functional role of gut microbiota in the pathophysiology and progression of cancers in relation to obesity and its metabolic correlates. Therapeutic approaches aiding microbiota restoration in connection with cancer treatments will be discussed.

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Fig. 1: A schematic representation of the association between obesity, microbiota, and cancer.

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References

  1. World Health Organization (WHO). Fact-sheets on cardiovascular disease. 2017. Available at: https://www.who.int/en/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds).

  2. Arnold M, Leitzmann M, Freisling H, Bray F, Romieu I, Renehan A, et al. Obesity and cancer: an update of the global impact. Cancer Epidemiol. 2016;41:8–15.

    Article  PubMed  Google Scholar 

  3. Doll R, Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Canc Inst. 1981;66:1191–308.

    Article  CAS  Google Scholar 

  4. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348:1625–38.

    Article  PubMed  Google Scholar 

  5. Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K, et al. Body Fatness and Cancer–Viewpoint of the IARC Working Group. N Engl J Med. 2016;375:794–8.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Investig. 2011;121:2094–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Investig. 2007;117:175–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res. 2005;46:2347–55.

    Article  CAS  PubMed  Google Scholar 

  9. Lee JY, Sohn KH, Rhee SH, Hwang D. Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. J Biol Chem. 2001;276:16683–9.

    Article  CAS  PubMed  Google Scholar 

  10. Fantuzzi G, Faggioni R. Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leuk Biol. 2000;68:437–46.

    Article  CAS  Google Scholar 

  11. Lee BC, Lee J. Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. Biochim Biophys Acta. 2014;1842:446–62.

    Article  CAS  PubMed  Google Scholar 

  12. Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016;65:1038–48.

    Article  CAS  PubMed  Google Scholar 

  13. Poloz Y, Stambolic V. Obesity and cancer, a case for insulin signaling. Cell Death Dis. 2015;6:e2037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Clemmons DR, Underwood LE. Nutritional regulation of IGF-I and IGF binding proteins. Ann Rev Nutr. 1991;11:393–412.

    Article  CAS  Google Scholar 

  15. Plymate SR, Matej LA, Jones RE, Friedl KE. Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin. J Clin Endocrinol Metabol. 1988;67:460–4.

    Article  CAS  Google Scholar 

  16. Neuhouser ML, Aragaki AK, Prentice RL, Manson JE, Chlebowski R, Carty CL, et al. Overweight, obesity, and postmenopausal invasive breast cancer risk: a secondary analysis of the women’s health initiative randomized clinical trials. JAMA Oncol. 2015;1:611–21.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Park J, Kusminski CM, Chua SC, Scherer PE. Leptin receptor signaling supports cancer cell metabolism through suppression of mitochondrial respiration in vivo. Am J Pathol. 2010;177:3133–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chang CC, Wu MJ, Yang JY, Camarillo IG, Chang CJ. Leptin-STAT3-G9a signaling promotes obesity-mediated breast cancer progression. Cancer Res. 2015;75:2375–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lipsey CC, Harbuzariu A, Daley-Brown D, Gonzalez-Perez RR. Oncogenic role of leptin and Notch interleukin-1 leptin crosstalk outcome in cancer. World J Methodol. 2016;6:43–55.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Gunter MJ, Leitzmann MF. Obesity and colorectal cancer: epidemiology, mechanisms and candidate genes. J Nutr Biochem. 2006;17:145–56.

    Article  CAS  PubMed  Google Scholar 

  21. Mutoh M, Teraoka N, Takasu S, Takahashi M, Onuma K, Yamamoto M, et al. Loss of adiponectin promotes intestinal carcinogenesis in Min and wild-type mice. Gastroenterology. 2011;140:2000–8.

    Article  CAS  PubMed  Google Scholar 

  22. Liu Z, Brooks RS, Ciappio ED, Kim SJ, Crott JW, Bennett G, et al. Diet-induced obesity elevates colonic TNF-alpha in mice and is accompanied by an activation of Wnt signaling: a mechanism for obesityassociated colorectal cancer. J Nutr Biochem. 2012;23:1207–13.

    Article  CAS  PubMed  Google Scholar 

  23. Matsui S, Okabayashi K, Tsuruta M, Shigeta K, Seishima R, Ishida T, et al. Interleukin-13 and its signaling pathway is associated with obesity-related colorectal tumorigenesis. Cancer Sci. 2019;110:2156–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Sanford NN, Giovannucci EL, Ahn C, Dee EC, Mahal BA. Obesity and younger versus older onset colorectal cancer in the United States, 1998-2017. J Gastrointest Oncol. 2020;11:121–6.

    Article  PubMed  PubMed Central  Google Scholar 

  25. European Association for the Study of the Liver (EASL); European Association for the Study of547 Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64:1388–402.

  26. Rajesh Y, Sarkar D. Molecular Mechanisms Regulating Obesity-Associated Hepatocellular Carcinoma. Cancers. 2020;12:1290.

    Article  CAS  PubMed Central  Google Scholar 

  27. Larsson SC, Wolk A. Overweight, obesity and risk of liver cancer: a meta-analysis of cohort studies. Br J Cancer. 2007;97:1005–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371:569–78.

    Article  PubMed  Google Scholar 

  29. Singh S, Sharma AN, Murad MH, Buttar NS, El-Serag HB, Katzka DA, et al. Central adiposity is associated with increased risk of esophageal inflammation, metaplasia, and adenocarcinoma: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2013;11:1399–412.

    Article  PubMed  Google Scholar 

  30. Rubenstein JH, Shaheen NJ. Epidemiology, diagnosis, and management of esophageal adenocarcinoma. Gastroenterology. 2015;149:302–17.e1.

    Article  PubMed  Google Scholar 

  31. Bianconi E, Piovesan A, Facchin F, Beraudi A, Casadei R, Frabetti F, et al. An estimation of the number of cells in the human body. Ann Hum Biol. 2013;40:463–71.

    Article  PubMed  Google Scholar 

  32. Sommer F, Anderson JM, Bharti R, Raes J, Rosenstiel P. The resilience of the intestinal microbiota influences health and disease. Nature Rev Microbiol. 2017;15:630–8.

    Article  CAS  Google Scholar 

  33. Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, et al. Host-gut microbiota metabolic interactions. Science. 2012;336:1262–7.

    Article  CAS  PubMed  Google Scholar 

  34. Everard A, Geurts L, Van Roye M, Delzenne NM, Cani PD. Tetrahydro Iso-alpha Acids from Hops Improve Glucose Homeostasis and Reduce Body Weight Gain and Metabolic Endotoxemia in High-fat Diet-fed Mice. PLoS ONE. 2012;7:e33858.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, et al. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007;50:2374–83.

    Article  CAS  PubMed  Google Scholar 

  36. Marzullo P, Di Renzo L, Pugliese G, De Siena M, Barrea L, Muscogiuri G, et al. From obesity through gut microbiota to cardiovascular diseases: a dangerous journey. Int J Obes Suppl. 2020;10:35–49.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457:480–4.

    Article  CAS  PubMed  Google Scholar 

  38. Mitsuoka T, Hayakawa K. Die Faecalflora bei Menschen. I. Die Zusammensetzung der Faecalflora der verschiedenen Altergruppen [The fecal flora in man. I. Composition of the fecal flora of various age groups]. Zentralbl Bakteriol Orig A. 1973;223:333–42.

    CAS  PubMed  Google Scholar 

  39. Mueller S, Saunier K, Hanisch C, Norin E, Alm L, Midtvedt T, et al. Differences in fecal microbiota in different European study populations in relation to age, gender, and country: a cross-sectional study. Appl Environ Microbiol. 2006;72:1027–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Org E, Mehrabian M, Parks BW, Shipkova P, Liu X, Drake TA, Lusis AJ. Sex differences and hormonal effects on gut microbiota composition in mice. Gut Microbes. 2016;7:313–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Bolnick DI, Snowberg LK, Hirsch PE, Lauber CL, Org E, Parks B, et al. Individual diet has sex-dependent effects on vertebrate gut microbiota. Nat Commun. 2014;5:4500.

    Article  CAS  PubMed  Google Scholar 

  42. Fuhrman BJ, Feigelson HS, Flores R, Gail MH, Xu X, Ravel J, Goedert JJ. Associations of the fecal microbiome with urinary estrogens and estrogen metabolites in postmenopausal women. J Clin Endocrinol Metab. 2014;99:4632–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Schwabe RF, Jobin C. The microbiome and cancer. Nat Rev Cancer. 2013;13:800–12.

  44. Gérard P. Gut microbiota and obesity. Cell Mol Life Sci. 2016;73:147–62.

    Article  PubMed  CAS  Google Scholar 

  45. Lazar V, Ditu LM, Pircalabioru GG, Gheorghe I, Curutiu C, Holban AM, et al. Aspects of gut microbiota and immune system interactions in infectious diseases, immunopathology, and cancer. Front Immunol. 2018;9:1830.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Yu LC. Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: exploring a common ground hypothesis. J Biomed Sci. 2018;25:79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. de Martel C, Ferlay J, Franceschi S, Vignat J, Bray F, Forman D, et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol. 2012;13:607–15.

    Article  PubMed  Google Scholar 

  48. Schistosomes, liver flukes and Helicobacter pylori. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 7-14 June 1994. IARC Monogr Eval Carcinog Risks Hum. 1994;61:1-241.

  49. Wroblewski LE, Peek RM Jr. Helicobacter pylori in gastric carcinogenesis: mechanisms. Gastroenterol Clin North Am. 2013;42:285–98.

    Article  PubMed  PubMed Central  Google Scholar 

  50. 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;22:299–306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Dalmasso G, Cougnoux A, Delmas J, Darfeuille-Michaud A, Bonnet R. The bacterial genotoxin colibactin promotes colon tumor growth by modifying the tumor microenvironment. Gut Microbes. 2014;5:675–80.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Sears CL, Geis AL, Housseau F. Bacteroides fragilis subverts mucosal biology: from symbiont to colon carcinogenesis. J Clin Investig. 2014;124:4166–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Farrell JJ, Zhang L, Zhou H, Chia D, Elashoff D, Akin D, et al. Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer. Gut. 2012;61:582–8.

    Article  CAS  PubMed  Google Scholar 

  54. Zeng XT, Xia LY, Zhang YG, Li S, Leng WD, Kwong JS. Periodontal disease and incident lung cancer risk: a meta-analysis of cohort studies. J Periodontol. 2016;87:1158–64.

    Article  PubMed  Google Scholar 

  55. Hieken TJ, Chen J, Hoskin TL, Walther-Antonio M, Johnson S, Ramaker S, et al. The microbiome of aseptically collected human breast tissue in benign and malignant disease. Sci Rep. 2016;6:30751.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Xuan C, Shamonki JM, Chung A, Dinome ML, Chung M, Sieling PA, et al. Microbial dysbiosis is associated with human breast cancer. PLoS One. 2014;9:e83744.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Urbaniak C, Gloor GB, Brackstone M, Scott L, Tangney M, Reid G. The microbiota of breast tissue and its association with breast cancer. Appl Environ Microbiol. 2016;82:5039–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Wang H, Altemus J, Niazi F, Green H, Calhoun BC, Sturgis C, et al. Breast tissue, oral and urinary microbiomes in breast cancer. Oncotarget. 2017;8:88122–38.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Yang J, Tan Q, Fu Q, Zhou Y, Hu Y, Tang S, Zhou Y, et al. Gastrointestinal microbiome and breast cancer: correlations, mechanisms and potential clinical implications. Breast Cancer. 2017;24:220–8.

    Article  PubMed  Google Scholar 

  60. Shapira I, Sultan K, Lee A, Taioli E. Evolving concepts: how diet and the intestinal microbiome act as modulators of breast malignancy. ISRN Oncol. 2013;2013:693920.

    PubMed  PubMed Central  Google Scholar 

  61. Zaineddin AK, Vrieling A, Buck K, Becker S, Linseisen J, Flesch-Janys D, et al. Serum enterolactone and postmenopausal breast cancer risk by estrogen, progesterone and herceptin 2 receptor status. Int J Cancer. 2012;130:1401–10.

    Article  CAS  PubMed  Google Scholar 

  62. Onoue M, Kado S, Sakaitani Y, Uchida K, Morotomi M. Specific species of intestinal bacteria influence the induction of aberrant crypt foci by 1,2-dimethylhydrazine in rats. Cancer Lett. 1997;113:179–186.

    Article  CAS  PubMed  Google Scholar 

  63. Yu J, Feng Q, Wong SH, Zhang D, Liang QY, Qin Y, et al. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut. 2017;66:70–78.

    Article  CAS  PubMed  Google Scholar 

  64. Dai Z, Coker OO, Nakatsu G, Wu WKK, Zhao L, Chen Z, et al. Multi-cohort analysis of colorectal cancer metagenome identified altered bacteria across populations and universal bacterial markers. Microbiome. 2018;6:70.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Wong SH, Yu J. Gut microbiota in colorectal cancer: mechanisms of action and clinical applications. Nat Rev Gastroenterol Hepatol. 2019;16:690–704.

    Article  CAS  PubMed  Google Scholar 

  66. Dapito DH, Mencin A, Gwak GY, Pradere JP, Jang MK, Mederacke I, et al. Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell. 2012;21:504–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Yu LX, Yan HX, Liu Q, Yang W, Wu HP, Dong W, et al. Endotoxin accumulation prevents carcinogen-induced apoptosis and promotes liver tumorigenesis in rodents. Hepatology. 2010;52:1322–33.

    Article  CAS  PubMed  Google Scholar 

  68. Yoshimoto S, Loo TM, Atarashi K, Kanda H, Sato S, Oyadomari S, et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature. 2013;499:97–101.

    Article  CAS  PubMed  Google Scholar 

  69. Pai R, Tarnawski AS, Tran T. Deoxycholic acid activates beta-catenin signaling pathway and increases colon cell cancer growth and invasiveness. Mol Biol Cell. 2004;15:2156–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Gadaleta RM, Oldenburg B, Willemsen EC, Spit M, Murzilli S, Salvatore L, et al. Activation of bile salt nuclear receptor FXR is repressed by pro-inflammatory cytokines activating NF-κB signaling in the intestine. Biochim Biophys Acta. 2011;1812:851–8.

    Article  CAS  PubMed  Google Scholar 

  71. Sfanos KS, Canene-Adams K, Hempel H, Yu S-H, Simons B, Schaeffer A, et al. Bacterial prostatitis enhances 2-amino-1-methyl-6-phenylimidazo[4,5-β]pyridine (PhIP)-induced cancer at multiple sites. Cancer Prev Res. 2015;8:683–92.

    Article  CAS  Google Scholar 

  72. Shoskes DA, Altemus J, Polackwich AS, Tucky B, Wang H, Eng C. The urinary microbiome differs significantly between patients with chronic prostatitis/chronic pelvic pain syndrome and controls as well as between patients with different clinical phenotypes. Urology. 2016;92:26–32.

    Article  PubMed  Google Scholar 

  73. Shrestha E, White JR, Yu S-H, Kulac I, Ertunc O, De Marzo AM, et al. Profiling the urinary microbiome in men with positive versus negative biopsies for prostate cancer. J Urol. 2018;199:161–71.

    Article  PubMed  Google Scholar 

  74. Sfanos KS, Yegnasubramanian S, Nelson WG, De Marzo AM. The inflammatory microenvironment and microbiome in prostate cancer development. Nat Rev Urol. 2018;15:11–24.

    Article  PubMed  Google Scholar 

  75. Vignozzi L, Gacci M, Maggi M. Lower urinary tract symptoms, benign prostatic hyperplasia and metabolic syndrome. Nat Rev Urol. 2016;13:108–19.

    Article  CAS  PubMed  Google Scholar 

  76. Stringer AM, Gibson RJ, Logan RM, Bowen JM, Yeoh AS, Keefe DM. Faecal microflora and beta-glucuronidase expression are altered in an irinotecan-induced diarrhea model in rats. Cancer Biol Ther. 2008;7:1919–25.

    Article  CAS  PubMed  Google Scholar 

  77. Wallace BD, Wang H, Lane KT, Scott JE, Orans J, Koo JS, et al. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science. 2010;330:831–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Kang MJ, Kim HG, Kim JS, Oh DG, Um YJ, Seo CS, et al. The effect of gut microbiota on drug metabolism. Expert Opin Drug Metab Toxicol. 2013;9:1295–308.

    Article  CAS  PubMed  Google Scholar 

  79. 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;342:967–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Daillère R, Vétizou M, Waldschmitt N, Yamazaki T, Isnard C, Poirier-Colame V, et al. Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects. Immunity. 2016;45:931–43.

    Article  PubMed  CAS  Google Scholar 

  81. Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillère R, Hannani D, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science. 2013;342:971–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Ghoreschi K, Laurence A, Yang XP, Tato CM, McGeachy MJ, Konkel JE, et al. Generation of pathogenic T(H)17 cells in the absence of TGF-β signalling. Nature. 2010;467:967–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Zitvogel L, Ayyoub M, Routy B, Kroemer G. Microbiome and anticancer immunosurveillance. Cell. 2016;165:276–87.

    Article  CAS  PubMed  Google Scholar 

  84. Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N, Flament C, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350:1079–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Chaput N, Lepage P, Coutzac C, Soularue E, Le Roux K, Monot C, et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann Oncol. 2017;28:1368–79.

    Article  CAS  PubMed  Google Scholar 

  86. Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359:97–103.

    Article  CAS  PubMed  Google Scholar 

  87. 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;350:1084–9. https://doi.org/10.1126/science.aac4255.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359:91–97.

    Article  CAS  PubMed  Google Scholar 

  89. Luo J, Hendryx M, Manson JE, Figueiredo JC, LaBlanc ES, Barrington W, et al. Intentional weight loss and obesity-related cancer risk. JNCI Cancer Spectr. 2019;3:pkz054.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Schmid D, Leitzmann MF. Association between physical activity and mortality among breast cancer and colorectal cancer survivors: a systematic review and metanalysis. Ann Oncol. 2014;25:1293–311.

    Article  CAS  PubMed  Google Scholar 

  91. Vance V, Mourtzakis M, McCargar L, Hanning R. Weight gain in breast cancer survivors: prevalence, pattern and health consequences. Obes Rev. 2011;12:282–294.

    Article  CAS  PubMed  Google Scholar 

  92. Belligoli A, Bettini S, Busetto L. Bariatric surgery: Is a matter of cutting calories or cutting metabolic regulators? Curr Opin Endocr Metab Res. 2019;4:83–8.

    Article  Google Scholar 

  93. Carlsson LM, Peltonen M, Ahlin S, Anveden A, Bouchard C, Carlsson B, et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med. 2012;367:695–704.

    Article  CAS  PubMed  Google Scholar 

  94. Sjöström L, Gummesson A, Sjöström CD, Narbro K, Peltonen M, Wedel H, et al. Swedish Obese Subjects Study. Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects study): a prospective, controlled intervention trial. Lancet Oncol. 2009;10:653–62.

    Article  PubMed  Google Scholar 

  95. Afshar S, Kelly SB, Seymour K, Lara J, Woodcock S, Mathers JC. The effects of bariatric surgery on colorectal cancer risk: systematic review and meta-analysis. Obes Surg. 2014;24:1793–9.

    Article  PubMed  Google Scholar 

  96. Derogar M, Hull MA, Kant P, Östlund M, Lu Y, Lagergren J. Increased risk of colorectal cancer after obesity surgery. Ann Surg. 2013;258:983–8.

    Article  PubMed  Google Scholar 

  97. Mackenzie H, Markar SR, Askari A, Faiz O, Hull M, Purkayastha S, et al. Obesity surgery and risk of cancer. Br J Surg. 2018;105:1650–7.

    Article  CAS  PubMed  Google Scholar 

  98. Feigelson HS, Caan B, Weinmann S, Leonard AC, Powers JD, Yenumula PR. et al. Bariatric surgery is associated with reduced risk of breast cancer in both premenopausal and postmenopausal women. Ann Surg. 2020;272:1053–1059. https://doi.org/10.1097/SLA.0000000000003331.

    Article  PubMed  Google Scholar 

  99. Tremaroli V, Karlsson F, Werling M, Stahlman M, Kovatcheva-Datchary P, Olbers T, et al. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metabolism. 2015;22:228–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Palleja A, Kashani A, Allin KH, Nielsen T, Zhang C, Li Y, et al. Roux-en-Y GAstric Bypass Surgery of Morbidly Obese Patients Induces Swift and Persistent Changes of the Individual Gut Microbiota. Genome Med. 2016;8:67.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Aron-Wisnewsky J, Prifti E, Belda E, Ichou F, Kayser BD, Dao MC, et al. Major microbiota dysbiosis in severe obesity: fate after bariatric surgery. Gut. 2019;68:70–82.

    Article  CAS  PubMed  Google Scholar 

  102. Tarashi S, Siadat SD, Ahmadi Badi S, Zali M, Biassoni R, Ponzoni M, et al. Gut bacteria and their metabolites: which one is the defendant for colorectal cancer? Microorganisms. 2019;7:561.

    Article  CAS  PubMed Central  Google Scholar 

  103. Scott KP, Antoine JM, Midtvedt T, van Hemert S. Manipulating the gut microbiota to maintain health and treat disease. Microb Ecol Health Dis. 2015;26:25877.

    PubMed  Google Scholar 

  104. Bodnaruc AM, Prud’homme D, Blanchet R, Giroux I. Nutritional modulation of endogenous glucagon-like peptide-1 secretion: a review. Nutr Metab. 2016;13:92.

    Article  CAS  Google Scholar 

  105. Taper HS, Roberfroid MB. Nontoxic potentiation of cancer chemotherapy by dietary oligofructose or inulin. Nutr Cancer. 2000;38:1–5.

    Article  CAS  PubMed  Google Scholar 

  106. Cabreiro F, Au C, Leung KY, Vergara-Irigaray N, Cochemé HM, Noori T, et al. Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell. 2013;153:228–39. https://doi.org/10.1016/j.cell.2013.02.035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11:506–14.

    Article  PubMed  Google Scholar 

  108. Gomes AC, de Sousa RG, Botelho PB, Gomes TL, Prada PO, Mota JF. The additional effects of a probiotic mix on abdominal adiposity and antioxidant status: a double-blind, randomized trial. Obesity. 2017;25:30–38.

    Article  CAS  PubMed  Google Scholar 

  109. Cai S, Kandasamy M, Rahmat JN, Tham SM, Bay BH, Lee YK, et al. Lactobacillus rhamnosus GG ACtivation of Dendritic Cells and Neutrophils Depends on the Dose and Time of Exposure. J Immunol Res. 2016;2016:7402760.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Konishi H, Fujiya M, Tanaka H, Ueno N, Moriichi K, Sasajima J, et al. Probiotic-derived ferrichrome inhibits colon cancer progression via JNK-mediated apoptosis. Nat Commun. 2016;7:12365.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Li J, Sung CY, Lee N, Ni Y, Pihlajamäki J, Panagiotou G, et al. Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice. Proc Natl Acad Sci USA. 2016;113:E1306–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Vrieze A, Van Nood E, Holleman F, Salojärvi J, Kootte RS, Bartelsman JF, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143:913–6.e7.

    Article  CAS  PubMed  Google Scholar 

  113. Kootte RS, Levin E, Salojärvi J, Smits LP, Hartstra AV, Udayappan SD, et al. Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition. Cell Metab. 2017;26:611–9.e6.

    Article  CAS  PubMed  Google Scholar 

  114. Li J, Sung CY, Lee N, Ni Y, Pihlajamäki J, Panagiotou G, et al. Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice. Proc Natl Acad Sci USA. 2016;113:E1306–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Chen D, Wu J, Jin D, Wang B, Cao H. Fecal microbiota transplantation in cancer management: current status and perspectives. Int J Cancer. 2019;145:2021–31.

    Article  CAS  PubMed  Google Scholar 

  116. Sinh P, Barrett TA, Yun L. Clostridium difficile Infection and Inflammatory Bowel Disease: A Review. Gastroenterol Res Pract. 2011;2011:136064.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Healy ME, Lahiri S, Hargett SR, Chow JD, Byrne FL, Breen DS, et al. Dietary sugar intake increases liver tumor incidence in female mice. Sci Rep. 2016;6:22292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Caprio M, Infante M, Moriconi E, Armani A, Fabbri A, Mantovani G, et al. Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE). J Endocrinol Investig. 2019;42:1365–86.

    Article  CAS  Google Scholar 

  119. Chung HY, Park YK. Rationale, feasibility and acceptability of ketogenic diet for cancer treatment. J Cancer Prev. 2017;22:127–34.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Seyfried TN, Kiebish MA, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P. Metabolic management of brain cancer. Biochim Biophys Acta. 2011;1807:577–94.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Obesity Programs of nutrition, Education, Research and Assessment (OPERA) group members served as collaborators and approved the final version of the paper: Annamaria Colao, Carlo Alviggi, Sara Aprano, Rocco Barazzoni, Luigi Barrea, Francesco Beguinot, Annamaria Belfiore, Giuseppe Bellastella, Silvia Bettini, Giuseppe Bifulco, Maurizio Bifulco, Caterina Brasacchio, Filomena Bottiglieri, Luca Busetto, Brunella Capaldo, Massimiliano Caprio, Felipe Casanueva, Luigi Di Luigi, Andrea Di Nisio, Laura Di Renzo, Carolina Di Somma, Lorenzo Maria Donini, Katherine Esposito, Massimo Federici, Dario Giugliano, Lucio Gnessi, Gianluca Gortan Cappellari, Brunella Guida, Maria Angela Guzzardi, Daniela Laudisio, Andrea Lenzi, Alessia Liccardi, Carla Lubrano, Paolo Emidio Macchia, Silvia Magno, Paolo Marzullo, Davide Menafra, Silvia Migliaccio, Fabrizio Muratori, Giovanna Muscogiuri, Raffaele Napoli, Caterina Pelosini, Francesca Pivari, Rosario Pivonello, Eleonora Poggiogalle, Gabriella Pugliese, Gabriele Riccardi, Alberto Ritieni, Fiammetta Romano, Domenico Salvatore, Alessandro Sanduzzi, Ferruccio Santini, Silvia Savastano, Paolo Sbraccia, Giovanni Scambia Laura Soldati, Giovanni Spera, Maria Grazia Tarsitano, Dario Tuccinardi, Olga Vaccaro, Mary Venneri, Samir Sukkar, Roberto Vettor.

Funding

This article is published as part of a supplement funded by the scientific assistance of Panta Rei Impresa Sociale srl (https://www.panta-rei.eu/pantarei/).

Author information

Authors and Affiliations

  1. Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy

    Paolo Marzullo

  2. Laboratory of Metabolic Research, IRCCS Istituto Auxologico Italiano, Piancavallo, Verbania, Italy

    Paolo Marzullo

  3. Department of Medicine, University of Padova, Padova, Italy

    Silvia Bettini, Andrea Di Nisio, Luca Busetto & Roberto Vettor

  4. Department of Clinical Medicine and Surgery, Endocrinology Unit, University Faculty of Medicine Federico II of Naples, Naples, Italy

    Davide Menafra, Sara Aprano, Giovanna Muscogiuri, Luigi Barrea, Silvia Savastano & Annamaria Colao

  5. Cattedra Unesco “Educazione alla salute e allo sviluppo sostenibile”, Università “Federico II” di, Napoli, Naples, Italy

    Annamaria Colao, Annamaria Colao, Silvia Savastano, Fiammetta Romano, Giovanna Muscogiuri, Alessia Liccardi, Luigi Barrea, Gabriella Pugliese, Filomena Bottiglieri, Sara Aprano, Davide Menafra, Daniela Laudisio, Domenico Salvatore, Carolina Di Somma, Dario Giugliano, Brunella Capaldo, Gabriele Riccardi, Brunella Guida, Maurizio Bifulco, Katherine Esposito, Paolo Emidio Macchia, Francesco Beguinot, Annamaria Belfiore, Alberto Ritieni, Raffaele Napoli, Olga Vaccaro, Carlo Alviggi, Rosario Pivonello, Giuseppe Bellastella & Giuseppe Bifulco

  6. Pisa, Italy

    Silvia Magno, Maria Angela Guzzardi, Caterina Pelosini & Ferruccio Santini

  7. Roma, Italy

    Eleonora Poggiogalle, Mary Venneri, Maria Grazia Tarsitano, Laura Di Renzo, Dario Tuccinardi, Massimiliano Caprio, Andrea Lenzi, Paolo Sbraccia, Lucio Gnessi, Carla Lubrano, Giovanni Spera, Luigi Di Luigi & Giovanni Scambia

  8. Trieste, Italy

    Gianluca Gortan Capellari & Rocco Barazzoni

  9. Milano, Italy

    Francesca Pivari, Caterina Brasacchio & Laura Soldati

  10. Como, Italy

    Fabrizio Muratori

  11. Spagna, Italy

    Felipe Casanueva

  12. Genova, Italy

    Samir Sukkar

Authors
  1. Paolo Marzullo
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  2. Silvia Bettini
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  3. Davide Menafra
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  4. Sara Aprano
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  5. Giovanna Muscogiuri
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  6. Luigi Barrea
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  7. Silvia Savastano
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  8. Annamaria Colao
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Consortia

on behalf of the Obesity Programs of nutrition, Education, Research and Assessment (OPERA) group

  • Annamaria Colao
  • , Silvia Savastano
  • , Silvia Magno
  • , Andrea Di Nisio
  • , Fiammetta Romano
  • , Giovanna Muscogiuri
  • , Eleonora Poggiogalle
  • , Mary Venneri
  • , Alessia Liccardi
  • , Maria Grazia Tarsitano
  • , Luigi Barrea
  • , Laura Di Renzo
  • , Dario Tuccinardi
  • , Massimiliano Caprio
  • , Maria Angela Guzzardi
  • , Caterina Pelosini
  • , Gabriella Pugliese
  • , Filomena Bottiglieri
  • , Paolo Marzullo
  • , Sara Aprano
  • , Silvia Bettini
  • , Davide Menafra
  • , Gianluca Gortan Capellari
  • , Daniela Laudisio
  • , Francesca Pivari
  • , Caterina Brasacchio
  • , Andrea Lenzi
  • , Fabrizio Muratori
  • , Ferruccio Santini
  • , Luca Busetto
  • , Paolo Sbraccia
  • , Laura Soldati
  • , Domenico Salvatore
  • , Carolina Di Somma
  • , Laura Di Renzo
  • , Dario Giugliano
  • , Lucio Gnessi
  • , Brunella Capaldo
  • , Gabriele Riccardi
  • , Rocco Barazzoni
  • , Brunella Guida
  • , Maurizio Bifulco
  • , Katherine Esposito
  • , Roberto Vettor
  • , Paolo Emidio Macchia
  • , Andrea Di Nisio
  • , Felipe Casanueva
  • , Carla Lubrano
  • , Francesco Beguinot
  • , Giovanni Spera
  • , Annamaria Belfiore
  • , Luigi Di Luigi
  • , Laura Soldati
  • , Alberto Ritieni
  • , Raffaele Napoli
  • , Olga Vaccaro
  • , Samir Sukkar
  • , Carlo Alviggi
  • , Rosario Pivonello
  • , Giuseppe Bellastella
  • , Giovanni Scambia
  •  & Giuseppe Bifulco

Contributions

The authors’ responsibilities were as follows: PM, SB, DM, and SA concept of this paper and drafted the manuscript. GM, LB, SS, and AC revised the manuscript and approved the final version.

Corresponding author

Correspondence to Giovanna Muscogiuri.

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The authors declare no competing interests.

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Marzullo, P., Bettini, S., Menafra, D. et al. Spot-light on microbiota in obesity and cancer. Int J Obes 45, 2291–2299 (2021). https://doi.org/10.1038/s41366-021-00866-7

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  • DOI: https://doi.org/10.1038/s41366-021-00866-7

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