Fecal functional metagenomics reveals increased gut Bacillota/Pseudomonadota (Firmicutes/Proteobacteria) ratio and altered bacterial CAZyme profile in human colorectal cancer
摘要
Gut microbial dysbiosis has been implicated in the onset and/or progression of colorectal cancer (CC). We recently identified the emergence of low-abundance bacterial taxa affiliated with the phylum Bacillota in the gut microbiome of CC patients, as revealed by 16S rRNA gene amplicon sequencing. Here, we subjected the fecal samples from CC (n = 4) and healthy control (HC, n = 4) participants to functional metagenomics using the Illumina Novaseq 6000 platform. Metagenome-assembled genomes (MAGs) showed compositional differences among bacterial phylotypes in CC and HC. Species observed, richness (Chao1), and diversity (Shannon’s) were high in CC, whereas species abundance peaked in HC. The Bacillota to Pseudomonadota ratio was high (> 3-fold) in CC (2.45) as compared to HC (0.70). MAGs revealed a decline in the distribution frequency of COGs involved in carbohydrate transport and metabolism (G), inorganic ion transport and metabolism (P), and unknown function (S) in CC. However, CC and HC samples exhibited marginal variations in terms of G/P (1.29 and 1.18, respectively) and G/S (0.35 and 0.40, respectively) ratios. Analysis further revealed a significant increment in glycosyltransferases GT1, GT2 and GT4, particularly in CC. In contrast, the glycoside hydrolases GH5 and GH9 declined in CC. GT/GH ratios were found to increase > 2-fold in CC (3.94) compared with HC (1.37). The present pilot-scale dataset-specific work reflects perseverance of Bacillota, significant decline in Pseudomonadota, a stable G/P and G/S ratios and enrichment of glycosyltransfererases in CC. Further transcriptomic-based studies in larger cohorts are warranted to gain insights into the implications of dysbiosis and its pathophysiological relevance.