Identification of Gut Microbiota Profile Associated with Colorectal Cancer in Saudi Population

SIMPLE SUMMARY: Colorectal cancer (CRC) is the third most common malignancy in the world and is the second most common cancer in Saudi Arabia. The faecal-associated microbiota has been dynamically linked to CRC worldwide, which, in turn, may offer evidence for procarcinogenic bacterial effectors-associated with CRC pathophysiology. Studies in gut microbiome and CRC are lacking on Saudi population, which is unique in lifestyle, diet, and genetic backgrounds. Data from CRC-associated intestinal micobiome provided a deeper understanding of CRC and serve as baseline for CRC predicators. In this project, 16S rRNA (V3-V4) gene sequencing analyses coupled with patient’s demographic, diet, and clinical data were deployed to identify microbiota associated with late stages of CRC. Understanding CRC pathophysiology in relation to intestinal microbiota allows early screening of CRC and prognostic option, which has the potential to treat patients at early stage and follow up with patient status. This will result in better outcomes and more cost-effective treatments. This comprehensive approach stratified CRC patients resulting in a potential better health care. ABSTRACT: 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 analyze 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. A cluster of ortholog genes’ (COG) functional annotations and the 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 Streptococcus salivarius, S. parasanguins, S. anginosus, Lactobacillus mucosae, L. gasseri, Peptostreptococcus, Eubacterium, Aerococcus, Family XIII_AD3001 Group, Erysipelatoclostridium, Escherichia-Shigella, Klebsiella, Enterobacter, Alistipes, Ralstonia, and Pseudomonas (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 between 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 CRC and its potential implications for use in diagnostic, prevention, and treatment strategies.