The human microbiota is a complex ecosystem that colonizes body surfaces and interacts with host organ systems, especially the immune system. Since the composition of this ecosystem depends on a variety of internal and external factors, each individual harbors a unique set of microbes. These differences in microbiota composition make individuals either more or less susceptible to various diseases, including cancer. Specific microbes are associated with cancer etiology and pathogenesis and several mechanisms of how they drive the typical hallmarks of cancer were recently identified. Although most microbes reside in the distal gut, they can influence cancer initiation and progression in distant tissues, as well as modulate the outcomes of established cancer therapies. Here, we describe the mechanisms by which microbes influence carcinogenesis and discuss their current and potential future applications in cancer diagnostics and management.

Department of Oncology 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Prague Czech Republic

Laboratory of Cellular and Molecular Immunology Institute of Microbiology v v i Czech Academy of Sciences Vídeňská 1083 142 00 Prague 4 Krč Czech Republic

See more in PubMed

Abrams GD, Bauer H, Sprinz H (1963) Influence of the normal flora on mucosal morphology and cellular renewal in the ileum. A comparison of germ-free and conventional mice. Lab Invest 12:355–364 PubMed

Akazawa Y, Cazanave S, Mott JL et al (2010) Palmitoleate attenuates palmitate-induced Bim and PUMA up-regulation and hepatocyte lipoapoptosis. J Hepatol 52(4):586–593 PubMed PMC

Alexander JL, Wilson ID, Teare J et al (2017) Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat Rev Gastroenterol Hepatol 14(6):356–365 PubMed

Alpdundar Bulut E, Bayyurt Kocabas B, Yazar V et al (2020) Human gut commensal membrane vesicles modulate inflammation by generating M2-like macrophages and myeloid-derived suppressor cells. J Immunol 205(10):2707–2718 PubMed

Al-Sabbagh R, Sinicrope FA, Sellin JH et al (1996) Evaluation of short-chain fatty acid enemas: treatment of radiation proctitis. Am J Gastroenterol 91(9):1814–1816 PubMed

Arpaia N, Campbell C, Fan X et al (2013) Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504(7480):451–455 PubMed PMC

Auchtung TA, Fofanova TY, Stewart CJ et al (2018) Investigating colonization of the healthy adult gastrointestinal tract by fungi. mSphere. 10.1128/mSphere.00092-18 PubMed PMC

Aviello G, Knaus UG (2017) ROS in gastrointestinal inflammation: rescue or sabotage? Br J Pharmacol 174(12):1704–1718 PubMed PMC

Badoual C, Hans S, Rodriguez J et al (2006) Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clin Cancer Res 12(2):465–472 PubMed

Bajer L, Kverka M, Kostovcik M et al (2017) Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis. World J Gastroenterol 23(25):4548–4558 PubMed PMC

Balachandran VP, Luksza M, Zhao JN et al (2017) Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature 551(7681):512–516 PubMed PMC

Balmer ML, Ma EH, Thompson AJ et al (2020) Memory CD8(+) T cells balance pro- and anti-inflammatory activity by reprogramming cellular acetate handling at sites of infection. Cell Metab 32(3):457-467 e455 PubMed

Baruch EN, Youngster I, Ben-Betzalel G et al (2021) Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science 371(6529):602–609 PubMed

Bayik D, Tross D, Haile LA et al (2017) Regulation of the maturation of human monocytes into immunosuppressive macrophages. Blood Adv 1(26):2510–2519 PubMed PMC

Belkaid Y, Bouladoux N, Hand TW (2013) Effector and memory T cell responses to commensal bacteria. Trends Immunol 34(6):299–306 PubMed PMC

Berg RD, Garlington AW (1979) Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs in a gnotobiotic mouse model. Infect Immun 23(2):403–411 PubMed PMC

Bergounioux J, Elisee R, Prunier AL et al (2012) Calpain activation by the Shigella flexneri effector VirA regulates key steps in the formation and life of the bacterium’s epithelial niche. Cell Host Microbe 11(3):240–252 PubMed

Bertocchi A, Carloni S, Ravenda PS et al (2021) Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver. Cancer Cell 39(5):708–724 PubMed

Boesch M, Baty F, Rothschild SI et al (2021) Tumour neoantigen mimicry by microbial species in cancer immunotherapy. Br J Cancer 125(3):313–323 PubMed PMC

Broderick NA, Buchon N, Lemaitre B (2014) Microbiota-induced changes in drosophila melanogaster host gene expression and gut morphology. Mbio 5(3):e01117-e11114 PubMed PMC

Buchta Rosean C, Bostic RR, Ferey JCM et al (2019) Preexisting commensal dysbiosis is a host-intrinsic regulator of tissue inflammation and tumor cell dissemination in hormone receptor-positive breast cancer. Cancer Res 79(14):3662–3675 PubMed PMC

Camarillo-Guerrero LF, Almeida A, Rangel-Pineros G et al (2021) Massive expansion of human gut bacteriophage diversity. Cell 184(4):1098-1109 e1099 PubMed PMC

Cani PD, Jordan BF (2018) Gut microbiota-mediated inflammation in obesity: a link with gastrointestinal cancer. Nat Rev Gastroenterol Hepatol 15(11):671–682 PubMed

Castellarin M, Warren RL, Freeman JD et al (2012) PubMed PMC

Chaput N, Lepage P, Coutzac C et al (2017) Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann Oncol 28(6):1368–1379 PubMed

Chen W, Jin W, Hardegen N et al (2003) Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198(12):1875–1886 PubMed PMC

Chen S, Su T, Zhang Y et al (2020a) PubMed PMC

Chen Y, Qiu X, Wang W et al (2020b) Human papillomavirus infection and cervical intraepithelial neoplasia progression are associated with increased vaginal microbiome diversity in a Chinese cohort. BMC Infect Dis 20(1):629 PubMed PMC

Chen Z, Wang B, Dong J et al (2021) Gut microbiota-derived l-histidine/imidazole propionate axis fights against the radiation-induced cardiopulmonary injury. Int J Mol Sci 22(21):11436 PubMed PMC

Chronopoulos A, Kalluri R (2020) Emerging role of bacterial extracellular vesicles in cancer. Oncogene 39(46):6951–6960 PubMed PMC

Clark NM, Martinez LM, Murdock S et al (2020) Regulatory T cells support breast cancer progression by opposing IFN-gamma-dependent functional reprogramming of myeloid cells. Cell Rep 33(10):108482 PubMed PMC

Comerford SA, Huang Z, Du X et al (2014) Acetate dependence of tumors. Cell 159(7):1591–1602 PubMed PMC

Copland A, Sparrow A, Hart P et al (2019) Bacillus Calmette-Guerin induces PD-L1 expression on antigen-presenting cells via autocrine and paracrine interleukin-STAT3 circuits. Sci Rep 9(1):3655 PubMed PMC

Coutzac C, Jouniaux JM, Paci A et al (2020) Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer. Nat Commun 11(1):2168 PubMed PMC

Curiel TJ, Coukos G, Zou L et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10(9):942–949 PubMed

Curtis H et al (2012) Human microbiome project C: structure, function and diversity of the healthy human microbiome. Nature 486(7402):207–214 PubMed PMC

Dai Z, Coker OO, Nakatsu G et al (2018) Multi-cohort analysis of colorectal cancer metagenome identified altered bacteria across populations and universal bacterial markers. Microbiome 6(1):70 PubMed PMC

Dalmasso G, Cougnoux A, Delmas J et al (2014) The bacterial genotoxin colibactin promotes colon tumor growth by modifying the tumor microenvironment. Gut Microbes 5(5):675–680 PubMed PMC

Davar D, Dzutsev AK, McCulloch JA et al (2021) Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science 371(6529):595–602 PubMed PMC

David LA, Maurice CF, Carmody RN et al (2014) Diet rapidly and reproducibly alters the human gut microbiome. Nature 505(7484):559–563 PubMed PMC

Deleemans JM, Chleilat F, Reimer RA et al (2019) The chemo-gut study: investigating the long-term effects of chemotherapy on gut microbiota, metabolic, immune, psychological and cognitive parameters in young adult Cancer survivors; study protocol. BMC Cancer 19(1):1243 PubMed PMC

Denton AS, Andreyev HJ, Forbes A et al (2002) Systematic review for non-surgical interventions for the management of late radiation proctitis. Br J Cancer 87(2):134–143 PubMed PMC

Derosa L, Hellmann MD, Spaziano M et al (2018) Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann Oncol 29(6):1437–1444 PubMed PMC

Derosa L, Routy B, Thomas AM et al (2022) Intestinal PubMed PMC

Ding X, Li Q, Li P et al (2020) Fecal microbiota transplantation: a promising treatment for radiation enteritis? Radiother Oncol 143:12–18 PubMed

Doll R, Peto R (1981) The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst 66(6):1191–1308 PubMed

Donohoe DR, Collins LB, Wali A et al (2012) The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol Cell 48(4):612–626 PubMed PMC

Dubin K, Callahan MK, Ren B et al (2016) Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis. Nat Commun 7:10391 PubMed PMC

Dziubanska-Kusibab PJ, Berger H, Battistini F et al (2020) Colibactin DNA-damage signature indicates mutational impact in colorectal cancer. Nat Med 26(7):1063–1069 PubMed

Elkrief A, Derosa L, Kroemer G et al (2019) The negative impact of antibiotics on outcomes in cancer patients treated with immunotherapy: a new independent prognostic factor? Ann Oncol 30(10):1572–1579 PubMed

Ellingjord-Dale M, Christakoudi S, Weiderpass E et al (2021) Long-term weight change and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Int J Epidemiol. 10.1093/ije/dyab032 PubMed PMC

Ewaschuk JB, Diaz H, Meddings L et al (2008) Secreted bioactive factors from PubMed

Fabrega MJ, Aguilera L, Gimenez R et al (2016) Activation of immune and defense responses in the intestinal mucosa by outer membrane vesicles of commensal and probiotic PubMed PMC

Ferreira MR, Sands CJ, Li JV et al (2021) Impact of pelvic radiation therapy for prostate cancer on global metabolic profiles and microbiota-driven gastrointestinal late side effects: a longitudinal observational study. Int J Radiat Oncol Biol Phys 111(5):1204–1213 PubMed PMC

Flanagan L, Schmid J, Ebert M et al (2014) Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome. Eur J Clin Microbiol Infect Dis 33(8):1381–1390 PubMed

Flores R, Zhong G (2015) The chlamydia pneumoniae inclusion membrane protein Cpn1027 interacts with host cell Wnt signaling pathway regulator cytoplasmic activation/proliferation-associated protein 2 (Caprin2). PLoS ONE 10(5):e0127909 PubMed PMC

Flores R, Shi J, Fuhrman B et al (2012) Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study. J Transl Med 10:253 PubMed PMC

Fonseca DM, Hand TW, Han SJ et al (2015) Microbiota-dependent sequelae of acute infection compromise tissue-specific immunity. Cell 163(2):354–366 PubMed PMC

Frankel AE, Coughlin LA, Kim J et al (2017) Metagenomic shotgun sequencing and unbiased metabolomic profiling identify specific human gut microbiota and metabolites associated with immune checkpoint therapy efficacy in melanoma patients. Neoplasia 19(10):848–855 PubMed PMC

Fung TC, Bessman NJ, Hepworth MR et al (2016) Lymphoid-tissue-resident commensal bacteria promote members of the IL-10 cytokine family to establish mutualism. Immunity 44(3):634–646 PubMed PMC

Furusawa Y, Obata Y, Fukuda S et al (2013) Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504(7480):446–450 PubMed

Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9(3):162–174 PubMed PMC

Galvao-Moreira LV, da Cruz MC (2016) Oral microbiome, periodontitis and risk of head and neck cancer. Oral Oncol 53:17–19 PubMed

Geng F, Liu J, Guo Y et al (2017) Persistent exposure to porphyromonas gingivalis promotes proliferative and invasion capabilities, and tumorigenic properties of human immortalized oral epithelial cells. Front Cell Infect Microbiol 7:57 PubMed PMC

Goedert JJ, Jones G, Hua X et al (2015) Investigation of the association between the fecal microbiota and breast cancer in postmenopausal women: a population-based case-control pilot study. J Natl Cancer Inst. 10.1093/jnci/djv147 PubMed PMC

Gopalakrishnan V, Spencer CN, Nezi L et al (2018) Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 359(6371):97–103 PubMed PMC

Griffin ME, Espinosa J, Becker JL et al (2021) Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy. Science 373(6558):1040–1046 PubMed PMC

Guo S, Chen J, Chen F et al (2020) Exosomes derived from Fusobacterium nucleatum-infected colorectal cancer cells facilitate tumour metastasis by selectively carrying miR-1246/92b-3p/27a-3p and CXCL16. Gut. 10.1136/gutjnl-2020-321187 PubMed

Gupta VK, Paul S, Dutta C (2017) Geography, ethnicity or subsistence-specific variations in human microbiome composition and diversity. Front Microbiol 8:1162 PubMed PMC

Gur C, Ibrahim Y, Isaacson B et al (2015) Binding of the Fap2 protein of PubMed PMC

Gur C, Maalouf N, Shhadeh A et al (2019) PubMed PMC

Haghi F, Goli E, Mirzaei B et al (2019) The association between fecal enterotoxigenic PubMed PMC

Han T, Hu X, Li K et al (2021) PubMed PMC

Hanahan D (2022) Hallmarks of cancer: new dimensions. Cancer Discov 12(1):31–46 PubMed

Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674 PubMed

Hansen CH, Nielsen DS, Kverka M et al (2012) Patterns of early gut colonization shape future immune responses of the host. PLoS ONE 7(3):e34043 PubMed PMC

Hapfelmeier S, Lawson MA, Slack E et al (2010) Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science 328(5986):1705–1709 PubMed PMC

Harusato A, Viennois E, Etienne-Mesmin L et al (2019) Early-life microbiota exposure restricts myeloid-derived suppressor cell-driven colonic tumorigenesis. Cancer Immunol Res 7(4):544–551 PubMed PMC

Hayes MA (1949) Chronic ulcerative colitis and associated carcinoma. Am J Surg 77(3):363–370 PubMed

He Z, Gharaibeh RZ, Newsome RC et al (2019) Campylobacter jejuni promotes colorectal tumorigenesis through the action of cytolethal distending toxin. Gut 68(2):289–300 PubMed PMC

He Y, Fu L, Li Y et al (2021) Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8(+) T cell immunity. Cell Metab 33(5):988-1000 e1007 PubMed

Hegazy AN, West NR, Stubbington MJT et al (2017) Circulating and tissue-resident CD4(+) T cells with reactivity to intestinal microbiota are abundant in healthy individuals and function is altered during inflammation. Gastroenterology 153(5):1320-1337 e1316 PubMed PMC

Hieken TJ, Chen J, Hoskin TL et al (2016) The microbiome of aseptically collected human breast tissue in benign and malignant disease. Sci Rep 6:30751 PubMed PMC

Hirano T (2021) IL-6 in inflammation, autoimmunity and cancer. Int Immunol 33(3):127–148 PubMed PMC

Hoffmann C, Dollive S, Grunberg S et al (2013) Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents. PLoS ONE 8(6):e66019 PubMed PMC

Holdbrooks AT, Britain CM, Bellis SL (2018) ST6Gal-I sialyltransferase promotes tumor necrosis factor (TNF)-mediated cancer cell survival via sialylation of the TNF receptor 1 (TNFR1) death receptor. J Biol Chem 293(5):1610–1622 PubMed PMC

Holokai L, Chakrabarti J, Broda T et al (2019) Increased programmed death-ligand 1 is an early epithelial cell response to helicobacter pylori infection. PLoS Pathog 15(1):e1007468 PubMed PMC

Hu B, Elinav E, Huber S et al (2013) Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer. Proc Natl Acad Sci USA 110(24):9862–9867 PubMed PMC

Huang Y, Yang W, Liu H et al (2012) Effect of high-dose methotrexate chemotherapy on intestinal Bifidobacteria, Lactobacillus and PubMed

Huang Z, Wang J, Xu X et al (2019) Antibody neutralization of microbiota-derived circulating peptidoglycan dampens inflammation and ameliorates autoimmunity. Nat Microbiol 4(5):766–773 PubMed

IARC (2012) IARC: biological agents, vol 100. International Agency for Research on Cancer, Lyon

IARC (2018) IARC: RED meat and processed meat, vol 114. International Agency for Research on Cancer, Lyon PubMed

Ibrahim-Hashim A, Estrella V (2019) Acidosis and cancer: from mechanism to neutralization. Cancer Metastasis Rev 38(1–2):149–155 PubMed PMC

Iida N, Dzutsev A, Stewart CA et al (2013) Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342(6161):967–970 PubMed PMC

Inaba H, Sugita H, Kuboniwa M et al (2014) Porphyromonas gingivalis promotes invasion of oral squamous cell carcinoma through induction of proMMP9 and its activation. Cell Microbiol 16(1):131–145 PubMed PMC

Jackson DN, Theiss AL (2020) Gut bacteria signaling to mitochondria in intestinal inflammation and cancer. Gut Microbes 11(3):285–304 PubMed PMC

Jakubowska K, Pryczynicz A, Januszewska J et al (2016) Expressions of matrix metalloproteinases 2, 7, and 9 in carcinogenesis of pancreatic ductal adenocarcinoma. Dis Markers 2016:9895721 PubMed PMC

Jang BS, Chang JH, Chie EK et al (2020) Gut microbiome composition is associated with a pathologic response after preoperative chemoradiation in patients with rectal cancer. Int J Radiat Oncol Biol Phys 107(4):736–746 PubMed

Jia X, Lu S, Zeng Z et al (2020) Characterization of gut microbiota, bile acid metabolism, and cytokines in intrahepatic cholangiocarcinoma. Hepatology 71(3):893–906 PubMed

Jin Y, Dong H, Xia L et al (2019) The diversity of gut microbiome is associated with favorable responses to anti-programmed death 1 immunotherapy in Chinese patients with NSCLC. J Thorac Oncol 14(8):1378–1389 PubMed

Kadosh E, Snir-Alkalay I, Venkatachalam A et al (2020) The gut microbiome switches mutant p53 from tumour-suppressive to oncogenic. Nature 586(7827):133–138 PubMed PMC

Kalkeri R, Walters K, Van Der Pol W et al (2021) Changes in the gut microbiome community of nonhuman primates following radiation injury. BMC Microbiol 21(1):93 PubMed PMC

Katayama Y, Yamada T, Shimamoto T et al (2019) The role of the gut microbiome on the efficacy of immune checkpoint inhibitors in Japanese responder patients with advanced non-small cell lung cancer. Transl Lung Cancer Res 8(6):847–853 PubMed PMC

Kim YS, Kim J, Park SJ (2015) High-throughput 16S rRNA gene sequencing reveals alterations of mouse intestinal microbiota after radiotherapy. Anaerobe 33:1–7 PubMed

Kim IY, Kwon HY, Park KH et al (2017a) Anaphase-promoting complex 7 is a prognostic factor in human colorectal cancer. Ann Coloproctol 33(4):139–145 PubMed PMC

Kim OY, Park HT, Dinh NTH et al (2017b) Bacterial outer membrane vesicles suppress tumor by interferon-gamma-mediated antitumor response. Nat Commun 8(1):626 PubMed PMC

Kim JY, Whon TW, Lim MY et al (2020) The human gut archaeome: identification of diverse haloarchaea in Korean subjects. Microbiome 8(1):114 PubMed PMC

Kindt A, Liebisch G, Clavel T et al (2018) The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice. Nat Commun 9(1):3760 PubMed PMC

Klimesova K, Kverka M, Zakostelska Z et al (2013) Altered gut microbiota promotes colitis-associated cancer in IL-1 receptor-associated kinase M-deficient mice. Inflamm Bowel Dis 19(6):1266–1277 PubMed PMC

Komorowski AS, Pezo RC (2020) Untapped “-omics”: the microbial metagenome, estrobolome, and their influence on the development of breast cancer and response to treatment. Breast Cancer Res Treat 179(2):287–300 PubMed

Kostic AD, Chun E, Robertson L et al (2013) Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14(2):207–215 PubMed PMC

Krausova M, Korinek V (2014) Wnt signaling in adult intestinal stem cells and cancer. Cell Signal 26(3):570–579 PubMed

Kuen DS, Kim BS, Chung Y (2020) IL-17-producing cells in tumor immunity: friends or foes? Immune Netw 20(1):e6 PubMed PMC

Kulkarni AA, Ebadi M, Zhang S et al (2020) Comparative analysis of antibiotic exposure association with clinical outcomes of chemotherapy versus immunotherapy across three tumour types. ESMO Open 5(5):e000803 PubMed PMC

Kverka M, Tlaskalova-Hogenova H (2017) Intestinal microbiota: facts and fiction. Dig Dis 35(1–2):139–147 PubMed

Kwon SK, Park JC, Kim KH et al (2021) Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice. Gut. 10.1136/gutjnl-2021-324489 PubMed

Lanca T, Silva-Santos B (2012) The split nature of tumor-infiltrating leukocytes: Implications for cancer surveillance and immunotherapy. Oncoimmunology 1(5):717–725 PubMed PMC

Laniewski P, Ilhan ZE, Herbst-Kralovetz MM (2020) The microbiome and gynaecological cancer development, prevention and therapy. Nat Rev Urol 17(4):232–250 PubMed PMC

Lazar V, Ditu LM, Pircalabioru GG et al (1830) Aspects of gut microbiota and immune system interactions in infectious diseases, immunopathology, and cancer. Front Immunol 9:1830 PubMed PMC

Lee HS, Boulton IC, Reddin K et al (2007) Neisserial outer membrane vesicles bind the coinhibitory receptor carcinoembryonic antigen-related cellular adhesion molecule 1 and suppress CD4+ T lymphocyte function. Infect Immun 75(9):4449–4455 PubMed PMC

Levy M, Kolodziejczyk AA, Thaiss CA et al (2017) Dysbiosis and the immune system. Nat Rev Immunol 17(4):219–232 PubMed

Li B, Vincent A, Cates J et al (2009) Low levels of tumor necrosis factor alpha increase tumor growth by inducing an endothelial phenotype of monocytes recruited to the tumor site. Cancer Res 69(1):338–348 PubMed PMC

Li X, Chen Y, Qi H et al (2016) Synonymous mutations in oncogenesis and apoptosis versus survival unveiled by network modeling. Oncotarget 7(23):34599–34616 PubMed PMC

Li H, Boakye D, Chen X et al (2021) Association of body mass index with risk of early-onset colorectal cancer: systematic review and meta-analysis. Am J Gastroenterol 116(11):2173–2183 PubMed PMC

Limeta A, Ji B, Levin M et al (2020) Meta-analysis of the gut microbiota in predicting response to cancer immunotherapy in metastatic melanoma. JCI Insight. 10.1172/jci.insight.140940 PubMed PMC

Lin LY, Du LM, Cao K et al (2016) Tumour cell-derived exosomes endow mesenchymal stromal cells with tumour-promotion capabilities. Oncogene 35(46):6038–6042 PubMed PMC

Lin S, Li Y, Zamyatnin AA Jr et al (2018) Reactive oxygen species and colorectal cancer. J Cell Physiol 233(7):5119–5132 PubMed

Liu J, Zhang N, Li Q et al (2011) Tumor-associated macrophages recruit CCR6+ regulatory T cells and promote the development of colorectal cancer via enhancing CCL20 production in mice. PLoS ONE 6(4):e19495 PubMed PMC

Liu C, Chikina M, Deshpande R et al (2019a) Treg cells promote the SREBP1-dependent metabolic fitness of tumor-promoting macrophages via repression of CD8(+) T cell-derived interferon-gamma. Immunity 51(2):381-397 e386 PubMed PMC

Liu F, Li J, Guan Y et al (2019b) Dysbiosis of the gut microbiome is associated with tumor biomarkers in lung cancer. Int J Biol Sci 15(11):2381–2392 PubMed PMC

Liu J, Liu C, Yue J (2021) Radiotherapy and the gut microbiome: facts and fiction. Radiat Oncol 16(1):9 PubMed PMC

Lombardo E, Alvarez-Barrientos A, Maroto B et al (2007) TLR4-mediated survival of macrophages is MyD88 dependent and requires TNF-alpha autocrine signalling. J Immunol 178(6):3731–3739 PubMed

Lu H, Wang Q, Liu W et al (2021) Precision strategies for cancer treatment by modifying the tumor-related bacteria. Appl Microbiol Biotechnol 105(16–17):6183–6197 PubMed

Ma C, Han M, Heinrich B et al (2018) Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells. Science. 10.1126/science.aan5931 PubMed PMC

Macpherson AJ, Uhr T (2004) Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science 303(5664):1662–1665 PubMed

Mager LF, Burkhard R, Pett N et al (2020) Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy. Science 369(6510):1481–1489 PubMed

Maisonneuve C, Tsang DKL, Foerster EG et al (2021) Nod1 promotes colorectal carcinogenesis by regulating the immunosuppressive functions of tumor-infiltrating myeloid cells. Cell Rep 34(4):108677 PubMed

Marques-Fernandez F, Planells-Ferrer L, Gozzelino R et al (2013) TNFalpha induces survival through the FLIP-L-dependent activation of the MAPK/ERK pathway. Cell Death Dis 4:e493 PubMed PMC

Marshall BJ, Warren JR (1984) Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1(8390):1311–1315 PubMed

Marzec M, Zhang Q, Goradia A et al (2008) Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7–H1). Proc Natl Acad Sci USA 105(52):20852–20857 PubMed PMC

Mathiasen SL, Gall-Mas L, Pateras IS et al (2021) Bacterial genotoxins induce T cell senescence. Cell Rep 35(10):109220 PubMed

Matson V, Fessler J, Bao R et al (2018) The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 359(6371):104–108 PubMed PMC

Matsukawa H, Iida N, Kitamura K et al (2021) Dysbiotic gut microbiota in pancreatic cancer patients form correlation networks with the oral microbiota and prognostic factors. Am J Cancer Res 11(6):3163–3175 PubMed PMC

Miao R, Badger TC, Groesch K et al (2020) Assessment of peritoneal microbial features and tumor marker levels as potential diagnostic tools for ovarian cancer. PLoS ONE 15(1):e0227707 PubMed PMC

Michaud DS, Lu J, Peacock-Villada AY et al (2018) Periodontal disease assessed using clinical dental measurements and cancer risk in the ARIC study. J Natl Cancer Inst 110(8):843–854 PubMed PMC

Michels KB (2005) The role of nutrition in cancer development and prevention. Int J Cancer 114(2):163–165 PubMed

Mima K, Sukawa Y, Nishihara R et al (2015) PubMed PMC

Mima K, Nishihara R, Qian ZR et al (2016) Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut 65(12):1973–1980 PubMed PMC

Mira-Pascual L, Cabrera-Rubio R, Ocon S et al (2015) Microbial mucosal colonic shifts associated with the development of colorectal cancer reveal the presence of different bacterial and archaeal biomarkers. J Gastroenterol 50(2):167–179 PubMed

Mitra A, MacIntyre DA, Lee YS et al (2015) Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity. Sci Rep 5:16865 PubMed PMC

Mitra A, MacIntyre DA, Ntritsos G et al (2020) The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions. Nat Commun 11(1):1999 PubMed PMC

Montassier E, Gastinne T, Vangay P et al (2015) Chemotherapy-driven dysbiosis in the intestinal microbiome. Aliment Pharmacol Ther 42(5):515–528 PubMed

Morgillo F, Dallio M, Della Corte CM et al (2018) Carcinogenesis as a result of multiple inflammatory and oxidative hits: a comprehensive review from tumor microenvironment to gut microbiota. Neoplasia 20(7):721–733 PubMed PMC

Morikawa A, Kawabata A, Shirahige K et al (2022) Altered cervicovaginal microbiota in premenopausal ovarian cancer patients. Gene 811:146083 PubMed

Morton AM, Sefik E, Upadhyay R et al (2014) Endoscopic photoconversion reveals unexpectedly broad leukocyte trafficking to and from the gut. Proc Natl Acad Sci USA 111(18):6696–6701 PubMed PMC

Muegge BD, Kuczynski J, Knights D et al (2011) Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science 332(6032):970–974 PubMed PMC

Nam YD, Kim HJ, Seo JG et al (2013) Impact of pelvic radiotherapy on gut microbiota of gynecological cancer patients revealed by massive pyrosequencing. PLoS ONE 8(12):e82659 PubMed PMC

Nejman D, Livyatan I, Fuks G et al (2020) The human tumor microbiome is composed of tumor type-specific intracellular bacteria. Science 368(6494):973–980 PubMed PMC

Nenclares P, Bhide SA, Sandoval-Insausti H et al (2020) Impact of antibiotic use during curative treatment of locally advanced head and neck cancers with chemotherapy and radiotherapy. Eur J Cancer 131:9–15 PubMed

Nene NR, Reisel D, Leimbach A et al (2019) Association between the cervicovaginal microbiome, BRCA1 mutation status, and risk of ovarian cancer: a case-control study. Lancet Oncol 20(8):1171–1182 PubMed

Nigro G, Rossi R, Commere PH et al (2014) The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell protection and links microbes to gut epithelial regeneration. Cell Host Microbe 15(6):792–798 PubMed

Norenhag J, Du J, Olovsson M et al (2020) The vaginal microbiota, human papillomavirus and cervical dysplasia: a systematic review and network meta-analysis. BJOG 127(2):171–180 PubMed

Numasaki M, Fukushi J, Ono M et al (2003) Interleukin-17 promotes angiogenesis and tumor growth. Blood 101(7):2620–2627 PubMed

Obregon-Tito AJ, Tito RY, Metcalf J et al (2015) Subsistence strategies in traditional societies distinguish gut microbiomes. Nat Commun 6:6505 PubMed PMC

Ohue Y, Nishikawa H (2019) Regulatory T (Treg) cells in cancer: can Treg cells be a new therapeutic target? Cancer Sci 110(7):2080–2089 PubMed PMC

Okita Y, Koi M, Takeda K et al (2020) Fusobacterium nucleatum infection correlates with two types of microsatellite alterations in colorectal cancer and triggers DNA damage. Gut Pathog 12:46 PubMed PMC

Park J, Lee SE, Hur J et al (2015) M-CSF from cancer cells induces fatty acid synthase and PPARbeta/delta activation in tumor myeloid cells leading to tumor progression. Cell Rep 10(9):1614–1625 PubMed

Pender SL, Tickle SP, Docherty AJ et al (1997) A major role for matrix metalloproteinases in T cell injury in the gut. J Immunol 158(4):1582–1590 PubMed

Perez PF, Dore J, Leclerc M et al (2007) Bacterial imprinting of the neonatal immune system: lessons from maternal cells? Pediatrics 119(3):e724-732 PubMed

Pernigoni N, Zagato E, Calcinotto A et al (2021) Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis. Science 374(6564):216–224 PubMed

Perrone F, Belluomini L, Mazzotta M et al (2021) Exploring the role of respiratory microbiome in lung cancer: a systematic review. Crit Rev Oncol Hematol 164:103404 PubMed

Pomares Bascunana RA, Veses V, Sheth CC (2021) Effectiveness of fecal microbiota transplant for the treatment of PubMed

Ponziani FR, Bhoori S, Castelli C et al (2019) Hepatocellular carcinoma is associated with gut microbiota profile and inflammation in nonalcoholic fatty liver disease. Hepatology 69(1):107–120 PubMed

Qi X, Yun C, Pang Y et al (2021) The impact of the gut microbiota on the reproductive and metabolic endocrine system. Gut Microbes 13(1):1–21 PubMed PMC

Qin J, Li R, Raes J et al (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464(7285):59–65 PubMed PMC

Ray D, Kidane D (2016) Gut microbiota imbalance and base excision repair dynamics in colon cancer. J Cancer 7(11):1421–1430 PubMed PMC

Rebe C, Ghiringhelli F (2020) Interleukin-1beta and cancer. Cancers (basel) 12(7):1791 PubMed PMC

Reddy BS, MacFie J, Gatt M et al (2007) Commensal bacteria do translocate across the intestinal barrier in surgical patients. Clin Nutr 26(2):208–215 PubMed

Rescigno M, Urbano M, Valzasina B et al (2001) Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2(4):361–367 PubMed

Rey C, Chang YY, Latour-Lambert P et al (2020) Transcytosis subversion by M cell-to-enterocyte spread promotes PubMed PMC

Ridlon JM, Wolf PG, Gaskins HR (2016) Taurocholic acid metabolism by gut microbes and colon cancer. Gut Microbes 7(3):201–215 PubMed PMC

Rios-Covian D, Ruas-Madiedo P, Margolles A et al (2016) Intestinal short chain fatty acids and their link with diet and human health. Front Microbiol 7:185 PubMed PMC

Rogan MR, Patterson LL, Wang JY et al (2019) Bacterial manipulation of Wnt signaling: a host-pathogen Tug-of-Wnt. Front Immunol 10:2390 PubMed PMC

Roquilly A, Jacqueline C, Davieau M et al (2020) Alveolar macrophages are epigenetically altered after inflammation, leading to long-term lung immunoparalysis. Nat Immunol 21(6):636–648 PubMed

Round JL, Mazmanian SK (2009) The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 9(5):313–323 PubMed PMC

Routy B, Le Chatelier E, Derosa L et al (2018) Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359(6371):91–97 PubMed

Rutkowski MR, Stephen TL, Svoronos N et al (2015) Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation. Cancer Cell 27(1):27–40 PubMed PMC

Salgia NJ, Bergerot PG, Maia MC et al (2020) Stool microbiome profiling of patients with metastatic renal cell carcinoma receiving anti-PD-1 immune checkpoint inhibitors. Eur Urol 78(4):498–502 PubMed

Schirbel A, Kessler S, Rieder F et al (2013) Pro-angiogenic activity of TLRs and NLRs: a novel link between gut microbiota and intestinal angiogenesis. Gastroenterology 144(3):613-623 e619 PubMed PMC

Schwabe RF, Jobin C (2013) The microbiome and cancer. Nat Rev Cancer 13(11):800–812 PubMed PMC

Scott TA, Quintaneiro LM, Norvaisas P et al (2017) Host-microbe co-metabolism dictates cancer drug efficacy in PubMed PMC

Sheng Y, Li F, Qin Z (2018) TNF receptor 2 makes tumor necrosis factor a friend of tumors. Front Immunol 9:1170 PubMed PMC

Sica A, Mantovani A (2012) Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 122(3):787–795 PubMed PMC

Sica A, Schioppa T, Mantovani A et al (2006) Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer 42(6):717–727 PubMed

Sims TT, El Alam MB, Karpinets TV et al (2021) Gut microbiome diversity is an independent predictor of survival in cervical cancer patients receiving chemoradiation. Commun Biol 4(1):237 PubMed PMC

Sivan A, Corrales L, Hubert N et al (2015) Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350(6264):1084–1089 PubMed PMC

Slots J, Bragd L, Wikstrom M et al (1986) The occurrence of PubMed

Sobko T, Reinders CI, Jansson E et al (2005) Gastrointestinal bacteria generate nitric oxide from nitrate and nitrite. Nitric Oxide 13(4):272–278 PubMed

Sommer F, Nookaew I, Sommer N et al (2015) Site-specific programming of the host epithelial transcriptome by the gut microbiota. Genome Biol 16:62 PubMed PMC

Song X, Gao H, Lin Y et al (2014) Alterations in the microbiota drive interleukin-17C production from intestinal epithelial cells to promote tumorigenesis. Immunity 40(1):140–152 PubMed

Song X, Xin N, Wang W et al (2015) Wnt/beta-catenin, an oncogenic pathway targeted by PubMed PMC

Song P, Yang D, Wang H et al (2020) Relationship between intestinal flora structure and metabolite analysis and immunotherapy efficacy in Chinese NSCLC patients. Thorac Cancer 11(6):1621–1632 PubMed PMC

Sorbara MT, Pamer EG (2019) Interbacterial mechanisms of colonization resistance and the strategies pathogens use to overcome them. Mucosal Immunol 12(1):1–9 PubMed PMC

Spencer CN, McQuade JL, Gopalakrishnan V et al (2021) Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science 374(6575):1632–1640 PubMed PMC

Stappenbeck TS, Hooper LV, Gordon JI (2002) Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci USA 99(24):15451–15455 PubMed PMC

Sun L, Yang S, Deng Q et al (2020) Salmonella effector SpvB disrupts intestinal epithelial barrier integrity for bacterial translocation. Front Cell Infect Microbiol 10:606541 PubMed PMC

Takiishi T, Fenero CIM, Camara NOS (2017) Intestinal barrier and gut microbiota: shaping our immune responses throughout life. Tissue Barriers 5(4):e1373208 PubMed PMC

Tanoue T, Morita S, Plichta DR et al (2019) A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature 565(7741):600–605 PubMed

Tchakarska G, Sola B (2020) The double dealing of cyclin D1. Cell Cycle 19(2):163–178 PubMed PMC

Tezal M, Sullivan MA, Hyland A et al (2009) Chronic periodontitis and the incidence of head and neck squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 18(9):2406–2412 PubMed

Thaiss CA, Zeevi D, Levy M et al (2014) Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell 159(3):514–529 PubMed

Tiffany CR, Baumler AJ (2019) Dysbiosis: from fiction to function. Am J Physiol Gastrointest Liver Physiol 317(5):G602–G608 PubMed PMC

Togo A, Dufour JC, Lagier JC et al (2019) Repertoire of human breast and milk microbiota: a systematic review. Future Microbiol 14:623–641 PubMed

Tonneau M, Elkrief A, Pasquier D et al (2021) The role of the gut microbiome on radiation therapy efficacy and gastrointestinal complications: a systematic review. Radiother Oncol 156:1–9 PubMed

Tremblay W, Mompart F, Lopez E et al (2021) Cytolethal distending toxin promotes replicative stress leading to genetic instability transmitted to daughter cells. Front Cell Dev Biol 9:656795 PubMed PMC

Urbaniak C, Gloor GB, Brackstone M et al (2016) The microbiota of breast tissue and its association with breast cancer. Appl Environ Microbiol 82(16):5039–5048 PubMed PMC

Uribe-Herranz M, Rafail S, Beghi S et al (2020) Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response. J Clin Invest 130(1):466–479 PubMed PMC

van Nood E, Vrieze A, Nieuwdorp M et al (2013) Duodenal infusion of donor feces for recurrent PubMed

Veettil SK, Wong TY, Loo YS et al (2021) Role of diet in colorectal cancer incidence: umbrella review of meta-analyses of prospective observational studies. JAMA Netw Open 4(2):e2037341 PubMed PMC

Vetizou M, Pitt JM, Daillere R et al (2015) Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350(6264):1079–1084 PubMed PMC

Viaud S, Saccheri F, Mignot G et al (2013) The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 342(6161):971–976 PubMed PMC

Viennois E, Merlin D, Gewirtz AT et al (2017) Dietary emulsifier-induced low-grade inflammation promotes colon carcinogenesis. Cancer Res 77(1):27–40 PubMed PMC

Vitali F, Colucci R, Di Paola M et al (2022) Early melanoma invasivity correlates with gut fungal and bacterial profiles. Br J Dermatol 186(1):106–116 PubMed PMC

Wang Y, Kuang Z, Yu X et al (2017) The intestinal microbiota regulates body composition through NFIL3 and the circadian clock. Science 357(6354):912–916 PubMed PMC

Wang T, Fan C, Yao A et al (2018) The adaptor protein CARD9 protects against colon cancer by restricting mycobiota-mediated expansion of myeloid-derived suppressor cells. Immunity 49(3):504-514 e504 PubMed PMC

Warburg O (1956) On the origin of cancer cells. Science 123(3191):309–314 PubMed

Watson RW, Rotstein OD, Parodo J et al (1998) The IL-1 beta-converting enzyme (caspase-1) inhibits apoptosis of inflammatory neutrophils through activation of IL-1 beta. J Immunol 161(2):957–962 PubMed

Wei LH, Kuo ML, Chen CA et al (2001) The anti-apoptotic role of interleukin-6 in human cervical cancer is mediated by up-regulation of Mcl-1 through a PI 3-K/Akt pathway. Oncogene 20(41):5799–5809 PubMed

Wei Z, Cao S, Liu S et al (2016) Could gut microbiota serve as prognostic biomarker associated with colorectal cancer patients’ survival? A pilot study on relevant mechanism. Oncotarget 7(29):46158–46172 PubMed PMC

Wikoff WR, Anfora AT, Liu J et al (2009) Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci USA 106(10):3698–3703 PubMed PMC

Winter J, Letley D, Rhead J et al (2014) Helicobacter pylori membrane vesicles stimulate innate pro- and anti-inflammatory responses and induce apoptosis in Jurkat T cells. Infect Immun 82(4):1372–1381 PubMed PMC

Wroblewski LE, Peek RM Jr, Wilson KT (2010) Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev 23(4):713–739 PubMed PMC

Wu S, Morin PJ, Maouyo D et al (2003) Bacteroides fragilis enterotoxin induces c-Myc expression and cellular proliferation. Gastroenterology 124(2):392–400 PubMed

Wu S, Rhee KJ, Albesiano E et al (2009) A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med 15(9):1016–1022 PubMed PMC

Wu GD, Chen J, Hoffmann C et al (2011) Linking long-term dietary patterns with gut microbial enterotypes. Science 334(6052):105–108 PubMed PMC

Xiao L, Zhang Q, Peng Y et al (2020a) The effect of periodontal bacteria infection on incidence and prognosis of cancer: a systematic review and meta-analysis. Medicine (baltimore) 99(15):e19698 PubMed PMC

Xiao HW, Cui M, Li Y et al (2020b) Gut microbiota-derived indole 3-propionic acid protects against radiation toxicity via retaining acyl-CoA-binding protein. Microbiome 8(1):69 PubMed PMC

Xu J, Peng JJ, Yang W et al (2020) Vaginal microbiomes and ovarian cancer: a review. Am J Cancer Res 10(3):743–756 PubMed PMC

Yang Y, Weng W, Peng J et al (2017) PubMed PMC

Yatsunenko T, Rey FE, Manary MJ et al (2012) Human gut microbiome viewed across age and geography. Nature 486(7402):222–227 PubMed PMC

Ying S, Zeng DN, Chi L et al (2015) The influence of age and gender on skin-associated microbial communities in urban and rural human populations. PLoS ONE 10(10):e0141842 PubMed PMC

Yu T, Guo F, Yu Y et al (2017) Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell 170(3):548-563 e516 PubMed PMC

Zhang Q, Liu S, Parajuli KR et al (2017) Interleukin-17 promotes prostate cancer via MMP7-induced epithelial-to-mesenchymal transition. Oncogene 36(5):687–699 PubMed PMC

Zhang Q, Ma C, Duan Y et al (2021) Gut microbiome directs hepatocytes to recruit MDSCs and promote cholangiocarcinoma. Cancer Discov 11(5):1248–1267 PubMed PMC

Zheng D, Liwinski T, Elinav E (2020a) Interaction between microbiota and immunity in health and disease. Cell Res 30(6):492–506 PubMed PMC

Zheng Y, Fang Z, Xue Y et al (2020b) Specific gut microbiome signature predicts the early-stage lung cancer. Gut Microbes 11(4):1030–1042 PubMed PMC

Zhu Z, Huang J, Li X et al (2020) Gut microbiota regulate tumor metastasis via circRNA/miRNA networks. Gut Microbes 12(1):1788891 PubMed PMC

Zuo T, Wong SH, Lam K et al (2018) Bacteriophage transfer during faecal microbiota transplantation in PubMed PMC