Role of Fusobacteria in the serrated pathway of colorectal carcinogenesis

Abstract

Fusobacteria are associated with colorectal cancer (CRC) and are amplified during colorectal carcinogenesis. Compared to the adenoma-carcinoma sequence of carcinogenesis, serrated neoplasm has distinct clinical features and a different molecular background. We aimed to compare the gut microbiome between tubular adenoma (TA) and sessile serrated adenoma/polyp (SSA/P). Patients with TA, SSA/P, or CRC were recruited. Three pieces of colorectal mucosal tissue were obtained from each patient by endoscopic biopsy. 16S rRNA gene pyrosequencing and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) were performed. Among 26 enrolled patients, 8, 10, and 8 had TA, SSA/P, and CRC, respectively. The relative abundance of Fusobacteria did not differ significantly between the TA and SSA/P groups (4.3% and 1.9%, P = 0.739) but was higher in the CRC group (33.8%) than in the TA or SSA/P group, respectively (TA vs. CRC, P = 0.002, false discovery rate [FDR] = 0.023; SSA/P vs. CRC, P < 0.001, FDR = 0.001). PICRUSt revealed that most functions in the TA metagenome were similar to those in the SSA/P metagenome. The gut microbiome, including relative abundance of Fusobacteria, did not differ between TA and SSA/P, suggesting that Fusobacteria may contribute to both the serrated pathway and the adenoma-carcinoma sequence.

Gut microbiome of Moroccan colorectal cancer patients

“…This genus has been recurrently associated with CRC [20, 48, 50–53, 57, 96–98]. Moreover, Fusobacterium was not detected in healthy control samples, as it is a relatively uncommon bacterium in the gut microbiome.…”

Interpretable machine learning analysis of functional metagenomic profiles improves colorectal cancer prediction and reveals basic molecular mechanisms.

“…Supplementary Figure 5 contains the most relevant features, which include proteins with functionalities related to CCR, such as amino acid metabolism [56], redox metabolism [57] or more generic biomarkers of bacterial proliferation [58]. Also, some specific features of adenoma, like the coenzyme F420 hydrogenase subunit beta, related to methane metabolism, enhanced in adenoma patients [41], or the chemotaxis protein methyltransferase CheR and the pilus assembly protein FimV, both related to chemotaxis and cell motility which have been described as a distinctive feature of adenomas [42], are also listed among the most relevant features. The most relevant feature, the large subunit ribosomal protein L19e, is an archaeal protein used as bad prognostic CRC biomarker [40].…”

“…Most of them are specific features of CRC that start to appear probably in the first adenoma stages previous to the cancer. Some of them are known CRC prognostic biomarkers, such as the archaeal large subunit ribosomal protein L19e [40], while other are characteristic of the adenoma stage, like the coenzyme F420 hydrogenase subunit beta, related to methane metabolism, enhanced in adenoma patients [41] or the chemotaxis protein methyltransferase CheR, which has been described as a distinctive feature of patients with adenomas [42].…”

Acetylcholinesterase Inhibitor Pyridostigmine Bromide Attenuates Gut Pathology and Bacterial Dysbiosis in a Murine Model of Ulcerative Colitis

“…The role of Flavobacteria in the human gut has not been clearly defined; however, Flavobacteria are less abundant in human IBD [67]. Similarly, the function of Fusobacteria in the gut are unknown, but their numbers increase in colorectal cancer [68], and UC increases susceptibility to colon cancer [69]. Therefore, it is likely that PB, through increased acetylcholine levels, (a) increases mucus formation and (b) inhibits the DSS-induced loss of the epithelial barrier function by suppressing IL-13 production.…”