Micorbiome profiling of fecal samples from colorectal cancer in Saudi population. Identification of Gut Microbiota Profile Associated with Colo-rectal Cancer in Saudi Population

Colorectal cancer (CRC) is a significant global health concern. Microbial dysbiosis and associated metabolites have been associated with CRC occurrence and progression. This study aims to ana-lyze the gut microbiota composition and the enriched metabolic pathways in patients with late-stage CRC. In this study, a cohort of 25 CRC patients diagnosed at late stage III and IV and 25 healthy participants were enrolled. The fecal bacterial composition was investigated using V3-V4 ribosomal RNA gene sequencing, followed by clustering and linear discriminant analysis (LDA) effect size (LEfSe) analyses. Cluster of ortholog genes (COG) functional annotation and Kyoto Encyclopedia of genes and genomes (KEGG) were employed to identify enrichment pathways between the two groups. The findings showed that the fecal microbiota between the two groups varied significantly in alpha and beta diversities. CRC patients’ fecal samples had significantly enriched populations of secondary bile acid (BA) producing bacteria, lactate producing bacteria, colibactin producing bacteria, sulfolipid producing bacteria, and opportunistic pathogens. Secondary BA producing bacteria include Strepto-coccus salivarius, S. parasanguins, S. anginosus, Lactobacillus mucosae, L. gasseri, Peptostrepto-coccus, Eubacterium, Clostridium innocuum group, Aerococcus, and Family XIII_AD3001 Group. Lac-tate producing bacteria that significantly increased in our CRC were S. salivarius, S. parasanguins, S. anginosus, L. mucosae, L. gasseri, and Erysipelatoclostridium (Q<0.05). Among our CRC, colibactin producing bacteria that showed significantly elevated levels were Escherichia-Shigella, Klebsiella, and Enterobacter (Q<0.05). Only one genus of sulfanolipid-producing bacteria was identified in our CRC, which was Alistipes. Two opportunistic bacterial pathogens, Ralstonia and Pseudomonas, had significantly increased levels in our CRC (Q<0.05). The enriched pathways identified in the CRC group were amino acid transport, signaling, and metabolism, membrane biogenesis, DNA replication and mismatch repair system, and protease activity (Q<0.05). These results suggested that the imbalance of intestinal bacteria and the elevated level of the predicated functions and pathways may contribute to the development of advanced CRC tumors. Further research is warranted to elucidate the exact role of the gut microbiome in colorectal cancer and its potential implications for diagnostic, prevention, and treatment strategies