Could gut microbiota serve as prognostic biomarker associated with colorectal cancer patients' survival? A pilot study on relevant mechanism

Abstract

Evidences have shown that dysbiosis could promote the progression of colorectal cancer (CRC). However, the association of dysbiosis and prognosis of CRC is barely investigated. Therefore, we used 16S rRNA gene sequencing approach to determine differences in microbiota among tumor tissues of different prognosis and found that Fusobacterium nucleatum and Bacteroides fragilis were more abundant in worse prognosis groups, while Faecalibacterium prausnitzii displayed higher abundance in survival group. To further explore the prognostic value of the found bacteria, Kaplan–Meier and Cox proportional regression analyses were used and the results exhibited that high abundance of F. nucleatum and B. fragilis were independent indicators of poor patient's survival. Besides, the expression of major inflammatory mediator were analyzed using PCR and western blot methods, and it turned out that high abundance of F. nucleatum was associated with increased expression of TNF-α, β-catenin and NF-κB, while COX-2, MMP-9 and NF-κB were positively related with high B. fragilis level, and high level of F. prausnitzii showed lower expression of β-catenin, MMP-9 and NF-κB. Moreover, immunohistochemical analysis indicated that KRAS and BRAF expression were prominent in F. nucleatum and B. fragilis high abundance group, while MLH1 showed lower expression. In conclusion, F. nucleatum, B. fragilis and F. prausnitzii can be identified as useful prognostic biomarkers for CRC, and dysbiosis might worsen the patients' prognosis by up-regulating gut inflammation level.

Structure and Function of the Fecal Microbiota in Diarrheic Neonatal Piglets

“…Fusobacterium is considered to be an inflammatory microorganism and a prognostic biomarker that inhibits T-cell responses and promotes the expression of inflammatory factors (Nosho et al, 2016; Wei et al, 2016). The increased relative abundance of Fusobacteriaceae in diarrheic piglets has also been reported in neonatal porcine diarrhea (Hermann-Bank et al, 2015) and horses with colitis (Costa et al, 2012).…”

Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

“…This is worth assessing in future studies, as in human studies and rodent models, overabundance of Fusobacterium spp. in patients or rodents with CRC does appear to have a correlation with poorer prognostic outcome 36, 51, 54…”

“…This probe array was selected to identify specific bacterial groups and individual bacterial species previously shown to be relevant in the pathogenesis of intestinal cancers in humans, rodents, and dogs. 9,14,19,22,23,27,[35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54] Tissue sections were bathed in 30μL of DNA-probe-hybridization buffer mix in a hybridization chamber maintained at 54 C overnight (12 hours). Buffer 1 (20mM Tris, 0.9M NaCl, 0.1% SDS, 20% Formamide, 10% Dextran sulfate) was used for the hybridization of Eub338, Erec482, Bacto1080, Fuso0664, Ebac1790 and Faecali698.…”

The role of intestinal bacteria in the development and progression of gastrointestinal tract neoplasms

“…These findings suggest an association between bacterial dysbiosis and the development of colorectal tumors. Studies have revealed an enrichment of Fusobacterium nucleatum in human colorectal adenomas and carcinomas compared with adjacent normal tissues [83,108–116]. Recent studies have demonstrated that a high amount of tissue Fusobacterium nucleatum is associated with advanced disease stage [108,109,117], a lower density of T cells in colorectal carcinoma tissue [83], and worse patient survival [111].…”

“…A few human studies have suggested a potential link between enterotoxigenic Bacteroides fragilis and colorectal cancer. Studies suggest that enterotoxigenic Bacteroides fragilis is detected significantly more often in the colon mucosa tissue or stool specimens of colorectal cancer cases than in the controls and that a higher amount of enterotoxigenic Bacteroides fragilis is associated with advanced disease stage [116,128,129]. Although experimental studies suggest that Enterococcus faecalis may promote the development of gastric and colorectal tumors [14–18], one clinical study has suggested that Enterococcus faecalis is detected significantly more often in the stool specimens of colorectal cancer cases than in the controls [130].…”