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. 2023 Aug 29;18(1):48.
doi: 10.1186/s13027-023-00523-w.

Evaluation of enterotoxigenic Bacteroides fragilis correlation with the expression of cellular signaling pathway genes in Iranian patients with colorectal cancer

Leila Dadgar-Zankbar  1 , Aref Shariati  2   3 , Narjess Bostanghadiri  1 , Zahra Elahi  1 , Shiva Mirkalantari  1 , Shabnam Razavi  1 , Fatemeh Kamali  4 , Davood Darban-Sarokhalil  5
Affiliations

Evaluation of enterotoxigenic Bacteroides fragilis correlation with the expression of cellular signaling pathway genes in Iranian patients with colorectal cancer

Leila Dadgar-Zankbar et al. Infect Agent Cancer. .

Abstract

Background: Colorectal cancer (CRC) is one of the most common cancers all over the world, and dysbiosis in the gut microbiota may play a role in colorectal carcinogenesis. Bacteroides fragilis can lead to tumorigenesis by changing signaling pathways, including the WNT/β-catenin pathway. Therefore, in the present study, we investigated the correlation between the enterotoxigenic B. fragilis amount and the expression of signaling pathway genes involved in CRC.

Materials and methods: B. fragilis was determined in 30 tumors and adjacent healthy tissues by the qPCR method. Next, the relationship between enterotoxigenic B. fragilis and the expression of signaling pathway genes, including CCND1, TP53, BCL2, BAX, WNT, TCF, AXIN, APC, and CTNNB1 was investigated. Additionally, possible correlations between clinicopathological features of the tumor samples and the abundance of B. fragilis were analyzed.

Results: The results showed that B. fragilis was detected in 100% of tumor samples and 86% of healthy tissues. Additionally, enterotoxigenic B. fragilis colonized 47% of all samples, and bft-1 toxin was the most frequently found isotype among the samples. The analysis showed that the high level of B. fragilis has a significant relationship with the high expression of AXIN, CTNNB1, and BCL2 genes. On the other hand, our results did not show any possible correlation between this bacterium and the clinicopathological features of the tumor sample.

Conclusion: B. fragilis had a higher abundance in the tumor samples than in healthy tissues, and this bacterium may lead to CRC by making changes in cellular signaling pathways and genes. Therefore, to better understand the physiological effects of B. fragilis on the inflammatory response and CRC, future research should focus on dissecting the molecular mechanisms by which this bacterium regulates cellular signaling pathways.

Keywords: BCL2; Bacteroides fragilis; Colorectal cancer; TP53; WNT/β-catenin.

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Conflict of interest statement

The authors declare that there are no potential conflicts of interest in the present study.

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Relative quantification of B. fragilis and signaling pathway genes. The relative quantity of B. fragilis (n = 30, p < 0.01**) was significantly higher in CRC samples than in adjacent normal tissues. The relative quantity of CTNNB1 (n = 30, p < 0.01**), BCL2, APC, TCF, WNT, and AXIN (n = 30, p < 0.05*) was significantly higher in CRC samples than in the adjacent normal tissues. BAX was higher in control tissues than in tumor tissues (p < 0.05*). On the other hand, there was no significant difference (ns) in the relative quantification of TP53 and CCND1 (n = 30, p > 0.05ns) between CRC samples and non-CRC tissues
Fig. 2
Fig. 2
Prevalence of B. fragilis toxin isotypes among Iranian patients with CRC. bft-1 was the most prevalent toxin in the samples (92.8%), one sample had bft-3 (7.2%), and no sample harbored bft-2 toxin
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