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Table 2 Summary of the main results of the included studies

From: Role of the intestinal microbiome in colorectal cancer surgery outcomes

Authors, yearBacteria1Bacterial characteristics in tissuesAssociation between microbiota composition and tumor stageResults
Short-term outcomes
 Van Praagh et al., 2017Lachnospiraceae
Bacteroidaceae
High abundance +
Low microbial diversity in patients with or without C-seal
Not reported- AL patients without a C-seal showed a significant lower microbial diversity, more Bacteroides, more Lachnospiraceae, and less Prevotella and Streptococci than C-seal patients who developed AL.
- AL cases of non-C-seal patients seem to be almost without exception dominated by Lachnospiraceae and Bacteroidaceae with correspondingly low microbial diversity scores
- Relation between the composition of the intestinal microbiota and the subsequent development of AL after stapled colorectal anastomoses, but only in patients who underwent surgery without the additional C-seal that covered the anastomoses
Long-term outcomes
 Flanagan et al., 2014F. nucleatumHigh vs. low or fold increase from normalNo significant differences between patients with no/low or high F. nucleatum, in TNM/Dukes staging.- A significant difference in survival between patients without detected F. nucleatum in tumor tissue or low fold increase vs. those with high fold increase.
- Median survival of subjects with high F. nucleatum fold increase is 2 years, whereas all subjects with low tumor to normal ratio survive more than 3 years (HR = 19.96, 95% CI = 1.42–281.42, p = 0.0266).
 Flemer et al., 2018Pathogen CAG
Prevotella CAG
Bacteroides CAG
Firmicutes CAG
Relative abundanceNot specified- Pathogen CAG-type microbiota was associated with longer survival (HR = 0.8, CI = 0.6–1.06; p = 0.12)
- Prevotella CAG-type microbiota was associated with longer survival (HR = 0.36, CI = 0.12–1.1; p = 0.075).
- Bacteroidetes CAG was associated with longer survival (HR = 0.75, CI = 0.58–1.03; p = 0.078).
- Firmicutes CAG 2 was associated with shorter survival (HR = 1.52, CI = 0.84–2.75; p = 0.17)
 Kosumi et al., 2018BifidobacteriumNegative vs. low vs. high DNA weightDifference in Bifidobacteria was not associated with disease stageNo significant associations of the amount of Bifidobacteria with colorectal cancer-specific mortality or overall mortality
 Mima et al., 2016F. nucleatumHigh vs. low vs. negative DNA loadThe amount of tissue F. NUCLEATUM DNA was associated with higher pT stage (p = 0.0007). The association was not statistically significant with pN or M stage.- Compared with F. nucleatum-negative cases, F. nucleatum-high cases had an HR = 1.58 (95% CI = 1.04–2.39) for cancer-specific mortality
- A higher amount of tissue F. nucleatum DNA was associated with shorter colorectal cancer-specific survival (p = 0.023) but no difference in overall mortality rate
 Wei et al., 2016B. fragilis
F. nucleatum
F. prausnitzii
High vs. low abundance- High abundance of F. nucleatum was significantly correlated with positive lymph node metastasis
- High abundance of F. prausnitzii and F. nucleatum was significantly correlated with worse depth of invasion
- Higher level of B. fragilis (9.75% vs. 2.62%, FDR = 0.017) in non-survival group than in survival group,
- F. prausnitzii (2.96% vs. 0.92%, FDR = 0.028) and Methylobacterium suomiense (1.91% vs. 0.78%, FDR = 0.098) were more abundant in the survival group.
- F. nucleatum was higher in non-survival group than survival group (5.66% vs. 1.08%, FDR = 0.076) and it exhibited a greater abundance in the recurrence group than in survival group (5.10% vs. 1.08%, FDR = 0.08)
- B. fragilis and F. prausnitzii might be correlated with patient’s survival in CRC
- 3-year OS was significantly lower in patients with high B. fragilis and F. nucleatum than in those with low abundance of these two microbiota (p = 0.001, p = 0.003).
- Low abundance of F. prausnitzii showed worse 3-year OS, (p = 0.06).
- B. fragilis (HR = 2.01; 95% CI = 1.02–3.96; p = 0.044) and F. nucleatum (HR = 1.99; 95% CI = 1.02–3.87; p = 0.042) were independent predictor of the 3-year OS
- B. fragilis (HR = 2.04; 95% CI = 1.11–3.73; p = 0.021) and F. nucleatum (HR = 1.82; 95% CI = 1–3.34; p = 0.05) were associated with poor 3-year DFS both
 Yan et al., 2017F. nucleatumHigh vs. low level- In both stage III and IV tumor, F. nucleatum level was significantly higher in CRC tissues than in adjacent normal tissues
- F. nucleatum was found to significantly associated with tumor invasion (p = 0.015), LNM status (p = 0.008), and distant metastasis (p = 0.020).
- Stage IIIA patients with low F. nucleatum level had no better CSS and DFS than those with high F. nucleatum level
- High F. nucleatum level was significantly associated with worse CSS and DFS in stage IIIB and IV patients
- Patients with high F. nucleatum level had a significantly worse CSS and DFS than those with low F. nucleatum level
For CSS: HR = 2.22; 95% CI = 1.48–3.32; p < 0.001
For DFS: HR = 2.0; 95% CI = 1.39–2.86; p < 0.001
 Yu et al., 2017F. nucleatumHigh vs. low amountThe amount of F. nucleatum was positively associated with the AJCC stage and tumor size- The 5-year RFS was substantially shorter in the F. nucleatum-high group than the F. nucleatum-low group.
- F. nucleatum was an independent predictor of CRC aggressiveness with significant HR for predicting clinical outcome. Its predictive value was comparable with that of the AJCC stage
  1. AL, anastomotic leakage; CAG, tissue-associated microbial co-abundance groups; CRC, colorectal cancer; HR, hazard ratios; OS, overall survival; CSS, cancer-specific survival; DFS, disease-free survival; RFS, recurrence-free survival; NS, not stated in the manuscript; LNM, lymph node metastasis
  2. 1Bacteria specifically associated with analyzed outcome