Association between colorectal cancer and Fusobacterium nucleatum and Bacteroides fragilis bacteria in Iranian patients: a preliminary study

Abstract

Background and aim Recent studies have proposed that commensal bacteria might be involved in the development and progression of gastrointestinal disorders such as colorectal cancer (CRC). Therefore, in this study, the relative abundance of Fusobacterium nucleatum, Bacteroides fragilis, Streptococcus bovis/gallolyticus, and Enteropathogenic Escherichia coli (EPEC) in CRC tissues, and their association with clinicopathologic characteristics of CRC was investigated in Iranian patients. Moreover, the role of these bacteria in the CRC-associated mutations including PIK3CA, KRAS, and BRAF was studied. Method To these ends, the noted bacteria were quantified in paired tumors and normal tissue specimens of 30 CRC patients, by TaqMan quantitative Real-Time Polymerase Chain Reaction (qPCR). Next, possible correlations between clinicopathologic factors and mutations in PIK3CA, KRAS, and BRAF genes were analyzed. Results In studied samples, B. fragilis was the most abundant bacteria that was detected in 66 and 60% of paired tumor and normal samples, respectively. Furthermore, 15% of the B. fragilis-positive patients were infected with Enterotoxigenic B. fragilis (ETBF) in both adenocarcinoma and matched adjacent normal samples. F. nucleatum was also identified in 23% of tumors and 13% of adjacent normal tissue samples. Moreover, the relative abundance of these bacteria determined by 2-ΔCT was significantly higher in CRC samples than in adjacent normal mucosa (p < 0.05). On the other hand, our findings indicated that S. gallolyticus and EPEC, compared to adjacent normal mucosa, were not prevalent in CRC tissues. Finally, our results revealed a correlation between F. nucleatum-positive patients and the KRAS mutation (p = 0.02), while analyses did not show any association between bacteria and mutation in PIK3CA and BRAF genes. Conclusion The present study is the first report on the analysis of different bacteria in CRC tissue samples of Iranian patients. Our findings revealed that F. nucleatum and B. fragilis might be linked to CRC. However, any link between gut microbiome dysbiosis and CRC remains unknown.

The Role of Fecal Fusobacterium nucleatum and pks+ Escherichia coli as Early Diagnostic Markers of Colorectal Cancer

“…Enrichment of F. nucleatum has been identified in CRC patients and is associated with worse outcomes [ 28 , 29 ]. CRC tissues have a higher abundance of F. nucleatum and B. fragilis bacteria than normal tissues in Iranian patients, and it has been recommended that the role of CRC-associated bacteria in CRC be further investigated in vivo and in vitro [ 30 ]. As it can be detected in both CRC tissues and feces of patients with CRC [ 31 ], F. nucleatum could serve as a potential marker for diagnosing patients with CRC.…”

High frequency of enterotoxigenic Bacteroides fragilis and Enterococcus faecalis in the paraffin-embedded tissues of Iranian colorectal cancer patients

“…Furthermore, Shariati et al (2021) showed a significantly higher abundance of B. fragilis and F. nucleatum in fresh frozen biopsies of colorectal lesions of Iranian CRC patients compared to adjacent normal mucosal tissues. However, they could not detect such a relation for S. gallolyticus and EPEC [ 16 ].…”

“…Their findings could potentially be explained through ethnic differences in susceptibility to colorectal colonization of S. gallolyticus or geographical differences in S. gallolyticus distribution. Furthermore, these discrepancies may also be related to application of diverse specimens (like fresh frozen tissues, FFPE and stool) and different detection methods (such as qPCR, pyrosequencing, Fluorescence In Situ Hybridization) used for detection of S. gallolyticus [ 1 , 5 , 16 ].…”

“…Furthermore, Bundgaard-Nielsen et al (2019) showed that F. nucleatum was distributed equally in tumors, paired normal tissue and diverticula, but significantly less present in adenomas [ 1 ]. However, F. nucleatum abundance in CRC patients varied between 13 and 87% in different countries [ 5 , 6 , 9 , 16 , 23 , 24 ]. According to Shariati et al (2021) and Kashani et al (2020) from Iran, F. nucleatum was highly abundant in CRC tissues (23 and 68%, respectively) compared to adjacent normal mucosa [ 16 , 24 ].…”

“…However, F. nucleatum abundance in CRC patients varied between 13 and 87% in different countries [ 5 , 6 , 9 , 16 , 23 , 24 ]. According to Shariati et al (2021) and Kashani et al (2020) from Iran, F. nucleatum was highly abundant in CRC tissues (23 and 68%, respectively) compared to adjacent normal mucosa [ 16 , 24 ]. Environmental factors such as weight, body mass index, diet, and geographical location may play an active role in bringing about this variation [ 16 ].…”