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. 2018 Jul 4;9(4):369-373.
doi: 10.1080/19490976.2018.1435246. Epub 2018 Apr 13.

Tumour-associated and non-tumour-associated microbiota: Addendum

Burkhardt Flemer  1   2 , Maeve Herlihy  3 , Micheal O'Riordain  3 , Fergus Shanahan  1   3 , Paul W O'Toole  1   2
Affiliations

Tumour-associated and non-tumour-associated microbiota: Addendum

Burkhardt Flemer et al. Gut Microbes. .

Abstract

In a recent study1 we reported that tissue-associated microbial Co-abundance Groups (CAGs) were differentially associated with colorectal cancer (CRC). Two of the CAGs, which we named Pathogen CAG and Prevotella CAG, were correlated with a gene expression signature indicative of a TH17 response. A TH17 response has been associated with decreased survival in patients with CRC2, and members of the Pathogen CAG such as Fusobacterium nucleatum, Escherichia coli and Bacteroides fragilis have been repeatedly reported to be associated with CRC-development. Thus we hypothesized that the abundance of these CAGs may be associated with poor survival. In this Addendum we extend our analysis of the at-surgery microbiota to microbiota profiles obtained after surgery for CRC which we analyzed in the context of survival data for patients with CRC. Surprisingly we found that high tissue-associated abundance of the previously defined Prevotella- and Pathogen-CAGs at surgery was associated with longer survival. Furthermore, we detected an association of the Bacteroidetes CAG in pre-surgery faecal microbiota with stability of the microbiota after surgery.

Keywords: colorectal cancer; gut microbiota; survival.

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Figures

Figure 1.
Figure 1.
AJCC staging is a strong prognostic marker for survival. The graph shows the Kaplan-Meier curves of 67 individuals, stratified below by tumour stage at surgery. Time is in days. Significance values were calculated using a Log-rank test.
Figure 2.
Figure 2.
Tumour-associated microbiota composition may be associated with disease prognosis in CRC. Shown are the Kaplan-Meier curves for individuals stratified by cancer-tissue-associated relative abundance of the Prevotella-CAG (A) and Firmicutes CAG 2 (B). All other variables (tumour stage, age, treatment, site) were kept constant. Strata: 1 = below or equal median abundance, n = 24; 2 = above median abundance, n = 23.
Figure 3.
Figure 3.
A CRC patient's faecal microbiota after surgery is similar to their microbiota before surgery. Shown is the PCoA based on the unweighted (top left panel) or weighted (top right panel) UniFrac distance and the Bray-Curtis distance (bottom left panel). P-values were determined using PERMANOVA. after: faecal microbiota of samples collected after surgical resection; before: faecal microbiota of samples collected before surgical resection.
Figure 4.
Figure 4.
The faecal microbiota profile before surgery correlates with stability of the microbiota after surgery. The plot shows the PCoA based on the Bray-Curtis distance. Circles: faecal microbiota before surgery. Arrow heads: faecal microbiota after surgery. The Bray-Curtis distance of the samples after surgery from their pre-surgery counterpart is smaller for samples in the left-bottom corner of the PCoA. Pearson's correlation coefficient ρ and P-values are given for the correlation between distance of samples after surgery from their pre-surgery counterpart and location of the pre-surgery sample on the PCoA. The colour of the arrows and the circles is associated with the Bray-Curtis distance of the sample after surgery from the sample before surgery (log-scale), as per the colour scale to the right.
Figure 5.
Figure 5.
The stability of the faecal microbiota after surgery is positively associated with the pre-surgery abundance of sporadic colonizers and negatively associated with the Bacteroidetes CAG and genus Lachnospira abundance. Graphs are the scatter-plots of the Bray-Curtis distance of samples after surgery compared to their pre-surgery sample (x-axis) and the combined centered log-ratio, pre-surgery abundance (y-axis) of bacteria found in less than 37% of individuals (i.e. bacteria which only sporadically colonize the human gut; panel to the left), of the Bacteroidetes CAG as defined in Supplementary Figure 2 (middle panel) and the genus Lachnospira (panel to the right). OTUs of this genus were mainly found in the Bacteroidetes CAG and had the highest negative correlation of all single genera with microbiota change after surgery. Linear regression trendlines are displayed.
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