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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, year Bacteria1 Bacterial characteristics in tissues Association between microbiota composition and tumor stage Results
Short-term outcomes
 Van Praagh et al., 2017 Lachnospiraceae
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., 2014 F. nucleatum High vs. low or fold increase from normal No 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., 2018 Pathogen CAG
Prevotella CAG
Bacteroides CAG
Firmicutes CAG
Relative abundance Not 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., 2018 Bifidobacterium Negative vs. low vs. high DNA weight Difference in Bifidobacteria was not associated with disease stage No significant associations of the amount of Bifidobacteria with colorectal cancer-specific mortality or overall mortality
 Mima et al., 2016 F. nucleatum High vs. low vs. negative DNA load The 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., 2016 B. 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., 2017 F. nucleatum High 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., 2017 F. nucleatum High vs. low amount The 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