Fig 1: Fecal LPS synthesis pathway is upregulated in CA patients.a Metagenomic shotgun data were used to compare relative gene abundance of bacterial metabolic pathways. Relative abundances of significantly different metabolic pathways are shown (n = 27 non-CA, n = 121 CA, two-sided Mann–Whitney U test with Benjamini–Hochberg FDR correction). b Relative abundance of significantly different LPS synthesis pathway-related genes between non-CA and CA individuals (two-sided Mann–Whitney U test with Benjamini–Hochberg FDR correction). c Batch-corrected LPB content in peripheral plasma of non-CA and CA individuals (n = 16 for non-CA, n = 47 for CA individuals, two-tailed unpaired t test with Welch’s correction). Average data are presented as mean ± s.e.m. Blue: non-CA individuals, red: CA patients.
Fig 2: Plasma and fecal microbiome as CA biomarkers.a Correlation between individual bacterial species and circulating factors. Correlation between species identified by multi-variate differential abundance and random forest analyses (Figs. 1 and 3, Supplementary Fig. 2) and individual plasma biomarkers. Degree of correlation is color coded (also see Supplementary Table 1, Pearson’s correlation testing; red: positive correlation; blue: negative correlation). b Correlation between combination of species identified based on clinical questions and circulating factors. Correlation between combination of bacterial species identified (in Figs. 1 and 3, Supplementary Fig. 2) and individual plasma biomarkers. Degree of correlation is color coded (also see Supplementary Table 1, Pearson’s correlation testing, red: positive correlation, blue: negative correlation). c–e Comparison of best ROC curve determined by combination of bacterial species identified in Fig. 3 and Supplementary Fig. 2, individual circulating factors, and bacterial species and individual circulating factors. c Distinction between sporadic/solitary and familial/multifocal CA patients (green: bacterial species identified in Supplementary Fig. 2 (B. dorei), blue: LPB, red: combined bacterial species and LPB). d Distinction between non-aggressive and aggressive CA patients (green: bacterial species identified in Fig. 3b, c, blue: IL-10, red: combined bacterial species and IL-10). e Distinction between non-CASH and CASH patients (CASH patient, green: bacterial species identified in Fig. 3g, h, blue: CRP, red: combined bacterial species and CRP). IFN? interferon-?, TNF tumor necrosis factor; CRP C-reactive protein, TLR4 toll-like receptor 4, VEGF vascular endothelial growth factor, THBS1 thrombospondin 1, TM thrombomodulin.
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