Table 2.
Intestinal microbial action on cancer mechanism
| No. | Types of cancer | Intestinal microbes | Molecules | Tumor promoter or suppressor | Mechanism | First author, year |
|---|---|---|---|---|---|---|
| 1 | Colon cancer | Fusobacterium nucleatum | Promoter | Fusobacterium nucleatum increases tumor multiplicity and selectively recruits tumor-infiltrating myeloid cells, which can promote tumor progression. | Kostic A.D., 2013 242 | |
| 2 | Colon cancer | Fusobacterium nucleatum | Promoter | Fap2 protein of F. nucleatum directly interacted with TIGIT, leading to the inhibition of NK cell cytotoxicity. | Gur C., 2015 130 | |
| 3 | Colon cancer | Fusobacterium nucleatum | Promoter | Fusobacterium nucleatum is inversely associated with CD3+ T-cell density in colorectal carcinoma tissue. | Mima K., 2015 188 |
|
| 4 | Colon cancer | Fusobacterium nucleatum | Fap2 (fusobacterial lectin) | Promoter | Fap2 mediates attachment of F. nucleatum to Gal-GalNAc which is highly expressed in human CRC, metastases, and a preclinical CRC model. | Abed J., 2016 131 |
| 5 | Colon cancer | Fusobacterium nucleatum | Promoter | F. nucleatum activates TLR4 signaling to MYD88, leading to activation of NFκB and increased expression of miR21; this miRNA reduces levels of the RAS GTPase RASA1. | Yang Y., 2017 243 | |
| 6 | Colon cancer | Fusobacterium nucleatum | Promoter | Fusobacterium nucleatum induces Annexin A1 expression in cancerous cells through FadA and E-cadherin, and FadA, E-cadherin, Annexin A1, and β-catenin form a complex. | Rubinstein M.R., 2019 133 | |
| 7 | Colon cancer |
Escherichia coli |
Promoter | Colibactin-producing E. coli contribute to the emergence of senescent cells, which enhance tumour promotion via growth factor secretion. | Cougnoux A., 2014 244 | |
| 8 | Colon cancer |
Escherichia coli |
Promoter | Colon cancer-associated E. coli bacteria induce COX-2 expression in human macrophages by p38 MAPK. | Raisch J.,2015 137 | |
| 9 | Colon cancer |
Bacteroides fragilis |
Promoter | ETBF-triggered colon tumorigenesis is associated with an IL-17-driven myeloid signature characterized by subversion of steady-state myelopoiesis in favor of the generation of protumoral monocytic-MDSCs. | Thiele Orberg E., 2017 141 | |
| 10 | Colon cancer |
Bacteroides fragilis |
Promoter | BFT triggers a pro-carcinogenic, multi-step inflflammatory cascade requiring IL-17R, NF-κB, and Stat3 signaling in colonic epithelial cells. | Chung L., 2018 140 | |
| 11 | Colon cancer | (1)Lachnospiraceae bacterium A4 (2)Helicobacter hepaticus (3) Mucispirillum schaedleri |
Suppressor; promoter; promoter | (1)Lachnospiraceae bacterium A4 is related to the production of Butyrate by promoting butyrate kinase synthes. (2)Helicobacter hepaticus has increased RNA counts of genes involved in oxidative phosphorylation,which suggests it exerts an oncogenic effect through oxidative damage. (3) Mucispirillum schaedleri is increasing inflammation through increased LPS production. |
Daniel S.G., 2017 127 | |
| 12 | Colon cancer | Commensal gut fungi | Suppressor | Commensal gut fungi mediate inflammasome activation by SYK-CARD9 Signaling Axis to restrict colon cancer. | Malik A., 2018 146 | |
| 13 | Colon cancer | Sirtuin-3 (Sirt3) | Suppressor | Gut microbiota (mainly Escherichia/Shigella, Lactobacillus reuteri and Lactobacillus taiwanensis) and Sirtuin-3 can interact with another and exert an anti-inflammatory and tumor-suppressing impact. | Zhang Y., 2018 245 | |
| 14 | Colon cancer | Campylobacter jejuni | Cytolethal distending toxin (microbial metabolites) |
Promoter | Campylobacter jejuni promotes colorectal cancer through the genotoxic action of cytolethal distending toxin, which has DNAse activity and causes DNA double-strand breaks. | He Z., 2019 144 |
| 15 | Colon cancer | P-cresol (microbial metabolites) |
Promoter | Exogenous p-cresol further increased DNA damage, and independently p-cresol induced DNA damage in a dose-dependent manner against HT29 and Caco-2 cells and influenced cell cycle kinetics. | Al Hinai E.A., 2019 246 | |
| 16 | Colon cancer | Flagellin (microbial componments) | Promoter | Flagellin increase IL6 and CCL2/MCP-1 mRNA and IL6 excretion and cytotoxicity, decrease caspase-1 activity and the production of reactive oxygen species of CRC cells. | Pekkala S., 2019 148 | |
| 17 | Colon cancer liver metastasis | Lipopolysaccharide (microbial componments) | promoter | LPS promote CRC metastasis by stimulating TLR4 signaling and increasing β1 integrin-mediated cell adhesion. | Hsu R.Y., 2011 247 | |
| 18 | Colon cancer liver metastasis | Lipopolysaccharide (microbial componments) | Promoter | Trapping LPS reduced liver metastasis of primary CRC and attenuated metastasized tumor growth in the liver. | Song W., 2018 248 | |
| 19 | Gastric cancer |
Helicobacter, intestinal commensals |
Promoter | The gastric carcinoma microbiota is dysbiotic and characterised by reduced microbial diversity, reduced Helicobacter abundance and over-representation of bacterial genera that include intestinal commensals.The microbial community found in gastric carcinoma has increased nitrosating functions consistent with increased genotoxic potential. | Ferreira RM, 2018 249 | |
| 20 | Gastric cancer | Helicobacter pylori | P-cresol (microbial metabolites) | Promoter | H. pylori increase proliferation in a strain-specific manner in a novel gastroid system. H. pylori also alter expression and localisation of claudin-7 in gastroids and human epithelial cells, which is mediated by β-catenin and snail activation. | Wroblewski LE, 2015 250 |
| 21 | Gastric cancer | Helicobacter pylori | CagPAI | Promoter | EMT-like morphological changes, specifically induced by cagPAI+ H. pylori in gastric epithelial cells, are associated to enhanced expression of mesenchymal genes and are regulated by a tripartite NF-κB/ZEB1 signaling pathway | Jessica Baud, 2013 251 |
| 22 | Gastric cancer | Helicobacter pylori | CagA | Promoter | Degradation of p53 induced by bacterial CagA protein is mediated by host HDM2 and ARF-BP1 E3 ubiquitin ligases, while the p14ARF protein counteracts H. pylori-induced signalling. | Jinxiong Wei, 2015 252 |
| 23 | Gastric cancer | Bacterial overgrowth and diversification |
Promoter | Lactobacillus and Lachnospiraceae uncultured are enriched in GAC. The gastric microbiota is altered in patients with GAC and is correlated with bacterial overgrowth and diversification. Enrichment of microbiota potentially associated with cancerpromoting activities. | Wang, 2016 253 | |
| 24 | Gastric cancer | LAB, oral bacterial species | SCFA, lactic | Promoter | 16S rRNA transcript sequencing Helicobacter pylori infection status affects overall constitution of the gastric microbiota. Increased bacterial diversity in GAC. Enrichment of proinflammatory oral bacterial species in GAC. Increased abundance of LAB and upregulated SCFAs production metabolism. | Castaño-Rodriguez, 2017 254 |
| 25 | Liver cancer | Bile acids | Promoter | The altered gut microbiota causes sustained retention of high concentrations of hepatic bile acids, and then promote liver carcinogenesis. | Xie G., 2016 27 | |
| 26 | Liver cancer | Lipoteichoic acid (microbial componments) deoxycholic acid (microbial metabolites) | Promoter | Deoxycholic acid and lipoteichoic acid derived from the gram-positive gut microbiota cooperated to upregulate the expression of SASP factors and COX2 in DCA-induced senescent hepatic stellate cells through TLR2. | Loo T.M., 2017 172 | |
| 27 | Liver cancer | Bile acid | Suppressor/promoter | Primary bile acids increases CXCL16 expression, which recruits CXCR6+ natural killer T cells to the liver, and mediate liver tumor inhibition, whereas secondary bile acids showed the opposite effect. | Ma C., 2018 10 | |
| 28 | Liver cancer | SCFA-producing bacteria | SCFA (microbial metabolites) | promoter | Dietary soluble fibers are fermented by gut bacteria into SCFAs, which promotes hepatocyte proliferation, liver fibrosis and induces cholestatic liver cancer. | Singh V., 2018 255 |
| 29 | Liver cancer | Interleukin-25 | promoter | Dysbiosis of gut microbiota results in secretion of IL-25, which promotes the progression of HCC through inducing alternative activation and CXCL10 secretion of macrophages in tumor microenvironment. | Li Q., 2019 256 | |
| 30 | Breast cancer |
Lithocholic acid (microbial metabolites) | Suppressor | Lithocholic acid can limit the proliferation of breast cancer cells in vitro and in vivo through activating TGR5 receptor. | Mikó E., 2018 257 | |
| 31 | Breast cancer |
Gut microbiome | Promoter | Commensal dysbiosis promoted early inflammation within the mammary gland, enhanced fibrosis and collagen deposition both systemically and locally within the tumor microenvironment and induced significant myeloid infiltration into the mammary gland and breast tumor. | Buchta Rosean C., 2019 258 | |
| 32 | Breast cancer |
Lithocholic acid (microbial metabolites) |
Suppressor | Lithocholic acid decreases nuclear factor E2-related factor 2 expression, increases KEAP1 expression via activation of TGR5 and constitutive androstane receptor, elicits oxidative stress that slows down the proliferation of breast cancer cells. | Kovács P., 2019 259 | |
| 33 | Breast cancer |
Cadaverine (microbial metabolites) | Suppressor | Cadaverine exerts fuctions through trace amino acid receptors to reduce breast cancer metastasis and induce a mesenchymal-to-epithelial transition and invasion. | Kovács T., 2019 260 | |
| 34 | Pancreatic cancer | Gut microbiome | Promoter | Gut microbiome interacts with immune system and affects cancer progression, gut microbiome depletion causes a significant anti-tumor influence in TME, such as increase in Th1 and Tc 1 cells. | Sethi V., 2018 121 | |
| 35 | Pancreatic cancer | Bifidobacterium pseudolongum | Promoter | A distinct gut microbiome was associated with immunogenic reprogramming of the PDAC tumor microenvironment. Bifidobacterium pseudolongum promoted mitigating M1 differentiation of macrophages. | Pushalkar S., 2018 120 | |
| 36 | Pancreatic cancer | Malassezia | Promoter | Malassezia acting as pathogenic fungi promote PDAC by driving the C3 complement cascade through the activation of MBL. | Aykut B., 2019 11 | |
| 37 | Esophagus cancer | Bile acids | Promoter | Bile acids exposed mice were easier to developed EAC and Barrett esophagus, with acute and chronic immune response, activate differential gene expression and expansion of gastric cardia progenitor cells. | Quante M., 2012 70 | |
| 40 | Esophagus cancer | Gut microbiome | Promoter | HFD promoted dysplasia by altering the esophageal micro-environment and gut microbiome, thereby inducing inflammation and stem cell expansion. | Münch N.S., 2019 69 | |
| 41 | Lung cancer | Propionate (microbial metabolites) | Suppressor | Propionate inhibited lung cancer cell proliferation by inducing cell cycle arrest, especially in the G2/M phase. It increased cleaved PARP-1 and caspase 3 expression by down- and upregulating survivin and p21. | Kim K., 2019 261 | |
| 42 | Melanoma | Bifidobacterium | Suppressor | Bifidobacterium showed a positive association with antitumor T cell responses within the tumor, and it promoted expression of genes associated with antitumor immunity of dendritic cells. | Sivan A., 2015 262 |