Table 1.
The role of commensal microbes in tumorigenesis and progression.
| Cancer type | Microbiome | Proposed mechanism |
|---|---|---|
| Gastric cancer | Helicobacter pylori | H. pylori is a cell toxin-associated antigen A (CagA) gene-positive bacterium that adheres to gastric epithelial cells by binding to the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) through outer membrane adhesin HopQ (22) and then delivers the effector protein CagA, peptidoglycan metabolites, and DNA directly to epithelial cells through a type IV secretion system (23). |
| Colorectal cancer | Bacteroides fragilis | Enterotoxigenic Bacteroides fragilis (ETBF) that produces the metalloprotease Bacteroides fragilis toxin (BFT) promotes inflammation and disrupts the intestinal barrier function by targeting the tight junctions of intestinal epithelial cells, which is associated with acute diarrhea and inflammatory bowel disease (27–29). |
| Escherichia coli | pks+ E. coli-derived colicin causes DNA damage in colonic epithelial cells (30, 31). | |
| Fusobacterium nucleatum | F. nucleatum has been shown to bind to host epithelial and endothelial cells through FadA adhesin and induce a series of inflammatory reactions mediated by NF-κB and IL-6 (32–34). | |
| Breast cancer |
Clostridiaceae, Faecalibacterium; Ruminococcaceae, Dorea Lachnospiraceae |
The gut microbiota may affect breast cancer risk and may do so through estrogen-independent pathways (35–37). |
| Fusobacterium nucleatum | Gal-GalNAc levels increase as human breast cancer progresses, and that occurrence of F. nucleatum gDNA in breast cancer samples correlates with high Gal-GalNAc levels (38). | |
| Lung cancer |
Veillonella and Megasphaera (39), Gram-negative bacilli Escherichia coli, Haemophilus influenzae, Staphylococcus spp., Candida albicans (40), Streptococcus (41) |
Local microbiota provoke inflammation associated with lung adenocarcinoma by activating lung-resident γδ T cells (42). |
| Skin cancer | S. aureus (43) | In squamous cell carcinoma (SCC), S. aureus might promote tumor cell growth via modulation of hBD-2 expression (43). |
| Corynebacterium (44, 45) | Corynebacterium species might affect the development of MM (malignant melanoma) through an IL-17-dependent pathway (44, 45). | |
| Pancreatic cancer | Fusobacterium nucleatum (46, 47), Granulicatella adiacens (47) | The possible association of tumor Fusobacterium species status with epigenetic alterations, such as MLH1 methylation and CpG island methylator phenotype (CIMP) in pancreatic cancer. |
| Proteobacteria (48, 49) | Proteobacteria lead to T-cell anergy in a Toll-like receptor-dependent manner, accelerating tumor progression (49). | |
| Malassezia globose (50, 51) | Contributes to tumorigenesis, tumor growth, and gemcitabine resistance via mannose-binding lectin-C3 axis (50, 52) | |
| Cervical cancer | Proteobacteria, Parabacteroides, Escherichia-Shigella, Roseburia (53) | The role of Prevotella in altering host immunity by modulating immunologic pathways may also be linked to cervical cancer risk and treatment outcomes (54). |
| Prevotella, Porphyromonas, Dialister (54) | ||
| Esophageal cancer | Fusobacterium nucleatum (55) | Contributes to tumor infiltration of Treg lymphocytes in a chemokine (especially CCL20)-dependent fashion, promoting aggressive tumor behaviors (55). |
| Campylobacter (56) | Campylobacter in esophageal adenocarcinoma progression might mimic that of Helicobacter pylori in gastric cancer (57, 58). | |
| Hepatocellular carcinoma | Clostridium (59) | Inhibition of DCA production and modulation of gut microbiota are effective in preventing tumorigenesis in HCC; however, Clostridium metabolizes bile acid into DCA, thus increasing the serum level of DCA (deoxycholic acid) 0p’in HCC (59, 60). |
| Salmonella typhi | Salmonella typhi strains that maintain chronic infections secrete AvrA, which can activate epithelial β-catenin signaling (61–63). | |
| Bacteroides and Ruminococcaceae | Bacteroides and Ruminococcaceae, can contribute to the development of hepatocellular carcinoma (HCC) by exacerbating hepatic inflammation, accumulating toxic compounds, and causing liver steatosis (64). |
HCC, hepatocellular carcinoma; DCA, deoxycholic acid.