A ABCA9 ALYREF ATIC CCDC28A CDC6 CDC7 CDCA7 Acidaminococcus Bilophila Butyricimonas Christensenellacese Clostridium obacterium Oscillospira Pseudomonas Sutterella Veillonella Ruminococcaceae B TAT ZNHITS ABCAB GINS2 CCDC28A PAICS CDCA7 Butyricimonas- Bilopha GINS1 EJF3J GENT4 TMEM97 OPP10 PTGFR LOR Haemophilus Clostridium Acidaminococcus UCP3 FAM111B Veillonella 0.75 MCM4 KIAREL3 MON1 ZC3H12A TFAM UNG TEX10 CMIP Christensencaceae DPP10 CDC6 Ruminococcaceae DUOX2 DUOXA2 EIF3J 0.5 Pseudomonas LCN2 Fusobacterium DUOXA2 ATIC LAPPRC MUCSAC, FAM111B RPLP2 CDC7 CMIP FAM120C TRHDE GCNT4 HELLS NUDCD1 Oscillospira DUOX2 TICAM1 GINS1 FAM120C GINS2 0.25 NUDT14 GSTO1 NAPSA HELLS ILDR1 KIRREL3 LCN2 LRPPRC MCM4 MDN1 MRPL17 MUCSAC NAPSA NUDCD1 NUDT14 PAICS PPP1R14B PTGFR RPLP2 SESN3 TAT TBX10 TFAM 0 -0.25 -0.5 TICAM1 TMEM97 TRHDE UCP3 UNG ZC3H12A ZNHIT6 -0.75 ZNHIT6 C DUOX2 2.00 1.75 1.50 1.25 rho=-0.675,q=0.083 Christensenellaceae rho-0.759.q=0.045 DUOXA2 LCN2 rho=-0.772.q=0.04 Ruminococcaceae rho-0.698.q=0.082 . -1 -5.0 -2.5 Butyricimonas 0.0 -75-50-25 DO 25 5.0 Veillonella Fig. 3 Interactions between genes associated with colorectal cancer and gut mucosal microbes. a Correlation plot depicting gene-microbe correlations. Color and size of the squares indicate the magnitude of the correlation, asterisks indicate significance of correlation (** indicates q value < 0.05 and indicates q value <0.1). b Network visualizing significant gene-microbe correlations (solid edges, q value <0.1) and significant microbe-microbe correlations (dashed edges, SparCC |R|>=0.1 and p value <0.05). Blue edges indicate positive correlation and red edges indicate negative correlation. Edge thickness represents the strength of the correlation. c Scatterplots depicting pattern of grouping by cystic fibrosis (red) and healthy (blue) samples in a few representative gene-microbe correlations, where the strength of correlation (Spearman rho) and significance (q) is indicated at the top of each plot and dashed edges represent microbe-microbe correla- tions. This subnetwork of microbe-microbe correlations depicts correlated abundance changes in the microbiome as a function of their presence (Fig. 3b, dashed edges). For instance, Bilophila and Butyricimonas are both de- pleted in CF (q value < 0.05), and the abundance of the two genera is also correlated across individuals (SparCC R-05 pseudo-n value-0.04) On the other hand solid edges), microbial nodes have more edges on aver- age compared to genes, where Christensenellaceae and Clostridium formed distinct hubs in the network. This potentially implies that these microbes and their path- ways are shared across multiple GI cancer-associated genes. Of note, Bilophila, Clostridium, and Pseudomonas are mostly negatively correlated with Gl cancer genes, while Haemophilus Oscillosnira Veillonella Eusobacter MacBook Pro