Table 1.
The Bacteria Discussed in This Review and Their Connections to Colorectal Cancer
| Increase or Reduction | Phyla–Class | Genus or Species (Subspecies) | Metabolism Effect | Mechanism | Clinicopathologic Features | Prognosis |
|---|---|---|---|---|---|---|
| Over- colonisation | Fusobacteria17,18,22 –Fusobacterium17,31 |
Fusobacterium nucleatum9,18,22,25,26,31-36,33,37,43,46,48,49 (subsp. Vincentii, subsp. animalis22) | / | Less E-cadherin on tumor cells9 Less infiltrating T cells9 More N-cadherin and nanog on tumor cells9 NK cells inhibition via Fap2 protein35 E-cadherin/β-catenin pathway36 Upregulation of REG3A, REG1A and REG1P49 |
NS between stages in Germany22 Abundant in early-stage26 Regional lymph node metastasis31 Liver metastasis32 MSI-H, CIMP-high, LINE-1 hypomethylation, and BRAF mutation33 Abundant at the ascending and transverse colons (compared to cecum, spleen to the sigmoid colon, sigmoid colon, and rectum)33 A linear trend from rectal cancer (2.5%) to cecal cancer (11%)34 Younger and black ethnicity patients in South African37 Over-colonization in stage III rather than I and II37 NS between ≤60 and >60 in Chinese43 Positive lymph node status and advanced tumor invasion43 Peak in stage II33 abundant in pT3 rather than pT1-233 NS between pN stages33 Poorly differentiated carcinoma46 Significant increase in inflammatory and DNA damage pathways49 |
Poorer overall survival and disease-free survival43 High disease-specific and disease-free survival in stage III or IV patients48 |
| Clostridia–Clostridiales |
Peptostreptococcus stomatis18,22,25 Peptostreptococcus anaerobius27 |
/ | / | / | / | |
| Clostridia–Clostridiales | Clostridium symbiosum22,42,43 | / | / | Peaking in stage II or III42 NS between ≤60 and >60 in Chinese43 Widespread tumor invasion43 |
/ | |
| Clostridia–Clostridiales | Parvimonas micra18,22,25,26 | / | / | Abundant in early-stage26 | / | |
| Bacteroidetes–Bacteroidetes | Enterotoxigenic Bacteroides fragilis (ETBF)28,37-40,43,47 | / | IL-17-dependent NF-κB activation in the colon epithelium39 CXCR2+ immature myeloid cells39 (Bft and IL-17) Activated colonic epithelial cells promote MDSC differentiation40 |
Higher in stage III and IV than stage I and II37 NS between ≤60 and >60 in Chinese43 An increasing trend from stage I to stage IV38 Low CD3+ T cell infiltration47 |
/ | |
| Bacteroidetes–Bacteroidetes | Bacteroides fragilis22,26,42,43,46,47 | / | / | Abundant in early-stage26 Peaking in stage II or III42 Intestinal extramural vascular invasion46 |
Poorer overall survival and disease-free survival43 | |
| Bacteroidetes–Bacteroidetes | Unclassified Prevotella22 Prevotella intermedia26,47 |
/ | / | Abundant in early-stage26 Low CD3+ T cell infiltration47 |
Shorter survival compared to high CD3+ T cell infiltration47 | |
| Bacteroidetes–Bacteroidetes | Alistipes finegoldii26 | / | / | Abundant in early-stage26 | / | |
| Bacteroidetes18–Bacteroidales | Porphyromonas asaccharolytica18,21,22,26 | / | / | Abundant in early-stage26 | / | |
| Firmicutes–Bacilli | Enterococcus faecalis28,49 | / | Upregulation of CXCL10 and BMI149 | MSI-H, CIMP-high49 Significant increase in inflammatory and DNA damage pathways49 |
/ | |
| Firmicutes46–Bacilli |
F. streptococcus spp.46 F. Solobacterium spp.46 Clostridium XI46 |
/ | / | Lymphatic vessel infiltration46 Poorly differentiated tumors46 |
/ | |
| Firmicutes17–Bacilli | Gemella spp.22 | / | / | / | / | |
| Firmicutes17–Bacilli | Lactococcus17 | / | / | / | / | |
| Firmicutes17–Clostridia | Thermanaerovibrio acidaminovorans26 | / | / | Abundant in early-stage26 | / | |
| Proteobacteria18–Gammaproteobacteria | afaC- or pks-Escherichia coli37,44 | / | Inflammatory cells infiltration44 | Over-colonization in stage T4 and M144 Relevance ratio peaks in stage II (I:43%, II:80%, III/IV:68%)44 |
/ | |
| Proteobacteria18–Gammaproteobacteria | Aggregatibacter spp.46 | / | / | KRAS mutations46 | / | |
| Actinobacteria–Actinobacteria | Atopobium21 | / | / | / | / | |
| / | Fretibacterium47 | / | / | Low CD3+ T cell infiltration47 | Shorter survival compared to high CD3+ T cell infiltration47 | |
| / | Solobacterium moorei25 | / | / | / | / | |
| Colonisation reduction | Firmicutes–Bacilli | Streptococcus salivarius22 | / | / | / | / |
| Firmicutes46–Clostridia | F. subdoligranulum46 | / | / | / | / | |
| Firmicutes–Clostridia | Faecalibacterium prausnitzii29,30 | / | / | / | / | |
| Firmicutes–Clostridia18,21,23 |
Coprococcus21 Lachnospiraceae21,42 |
Ferments dietary fiber and other complex carbohydrates into butyric acids21,23 | / | Peaking in stage II or III42 | / | |
| Firmicutes–Clostridia |
Eubacterium rectale22,23,29 Eubacterium ventriosum22,23,25 Eubacterium eligens22,23 |
Butyric acid-producing23 | / | / | / | |
| Firmicutes–Clostridia | Unclassified Ruminococcus sp.22,23 | Butyrate-producing bacteria23 | / | / | / | |
| Firmicutes–Clostridia | Lachnospiraceae18,43 | / | / | Abundant in surviving patients (compared to non-surviving ones)43 | / | |
| Proteobacteria–Alphaproteobacteria |
Methylobacterium43 Sphingomonas43 |
/ | / | Abundant in surviving patients (compared to non-surviving ones)43 Abundant in recurrence-free survival patients (compared to relapse ones)43 |
/ | |
| Proteobacteria–Deltaproteobacteria | Desulfovibrio47 | / | / | High CD3+ T cell infiltration47 | Longer survival compared to low CD3+ T cell infiltration47 | |
| Proteobacteria–Gammaproteobacteria | Shewanella43 | / | / | Abundant in surviving patients (compared to non-surviving ones)43 | / | |
| Proteobacteria17–Gammaproteobacteria |
Pseudomonas17 Escherichia-Shigella17 |
/ | / | / | / | |
| Spirochaetes–Spirochaetes | Treponema47 | / | / | High CD3+ T cell infiltration47 | Longer survival compared to low CD3+ T cell infiltration47 | |
| / | Alloprevotella47 | / | / | High CD3+ T cell infiltration47 | Longer survival compared to low CD3+ T cell infiltration47 |
Abbreviations: NK, nature killer; BRAF, B-Raf proto-oncogene, serine/threonine kinase; KRAS, KRAS proto-oncogene, GTPase; CD, cluster of differentiation; ETBF, enterotoxigenic Bacteroides fragilis; TNM, tumor, node, metastasis stage system; pN, pathological lymph node stage; REG, regenerating islet derived protein; MSI-H, high microsatellite instability; CIMP, CpG island methylator phenotype; LINE-1, long interspersed nuclear element-1; NS, no significance; IL-17, interleukin-17; NF-κB, NF-kappaB inhibitor alpha; CXCR2, C-X-C motif receptor; Bft, Bacteroides fragilis toxin; MDSC, myeloid-derived suppressor cell; CXCL10, C-X-C motif ligand; BMI1, B-cell-specific moloney leukemia virus insert site 1.