Gut Microbiota and Colon Cancer: A Role for Bacterial Protein Toxins?

Fiorentini, Carla; Carlini, Francesca; Germinario, Elena; Maroccia, Zaira; Travaglione, Sara; Fabbri, Alessia

doi:10.3390/ijms21176201

Cited by 36 publications

(27 citation statements)

References 183 publications

(207 reference statements)

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“…These effects can modulate cell proliferation, replication, and death, and coincidentally cause transformation and cellular malignancies. In this regard, evaluating the presence of bacterial toxins with oncogenic potential at the transcriptional or proteomic level will provide an additional layer of information to unravel complex host-pathogen interactions with relevance to CRC in the future [ 9 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

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

Shariati

Razavi

Ghaznavi‐Rad

et al. 2021

Infect Agents Cancer

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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.

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Section: Discussionmentioning

confidence: 99%

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

Shariati

Razavi

Ghaznavi‐Rad

et al. 2021

Infect Agents Cancer

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“…All these factors contribute to carcinogenesis. As in other types of cancer, in colorectal cancer, special emphasis has been placed on protein toxins produced by the intestinal microbiota [142]. The procarcinogenic effect of these toxins could be due to the direct attack on DNA, which leads to genomic instability or proliferation and induction of resistance to apoptosis in cancer derived from cellular signaling alterations [143].…”

Section: Colorectal Cancermentioning

confidence: 99%

Impact of the Gut Microbiota Balance on the Health–Disease Relationship: The Importance of Consuming Probiotics and Prebiotics

Olvera-Rosales

Cruz‐Guerrero

Ramírez‐Moreno

et al. 2021

Foods

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Gut microbiota is a group of microorganisms that are deposited throughout the entire gastrointestinal tract. Currently, thanks to genomic tools, studies of gut microbiota have pointed towards the understanding of the metabolism of important bacteria that are not cultivable and their relationship with human homeostasis. Alterations in the composition of gut microbiota could explain, at least in part, some epidemics, such as diabetes and obesity. Likewise, dysbiosis has been associated with gastrointestinal disorders, neurodegenerative diseases, and even cancer. That is why several studies have recently been focused on the direct relationship that these types of conditions have with the specific composition of gut microbiota, as in the case of the microbiota–intestine–brain axis. In the same way, the control of microbiota is related to the diet. Therefore, this review highlights the importance of gut microbiota, from its composition to its relationship with the human health–disease condition, as well as emphasizes the effect of probiotic and prebiotic consumption on the balance of its composition.

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“…B. fragilis toxin degrades E-cadherin, upregulates ROS production, promoting irreversible DNA damage, thus, contributing to colon cancer initiation. These mechanisms were recently nicely overviewed in-depth by Fiorentini C. et al [ 21 ]. Some cancer-promoting strains of Escherichia coli sp.…”

Section: Mechanistic Links Between Microbiota and Colon Cancermentioning

confidence: 99%

“…Some cancer-promoting strains of Escherichia coli sp. produce genotoxin colibactin, which is reported to contribute to genomic instability and tumor-promoting inflammation during cancerogenesis [ 21 ]. Cancer passenger bacterium F. nucleatum has been shown to promote colon cancer by activation of E-cadherin/β-catenin signaling via FadA adhesin [ 22 ].…”

Section: Mechanistic Links Between Microbiota and Colon Cancermentioning

confidence: 99%

Drug–Microbiota Interaction in Colon Cancer Therapy: Impact of Antibiotics

et al. 2021

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Colon adenocarcinoma is one of the most common malignancies, and it is highly lethal. Chemotherapy plays an important role in the treatment of colon cancer at various stages of the disease. The gut microbiome has emerged as a key player in colon cancer development and progression, and it can also alter the therapeutic agent’s efficacy and toxicities. Antibiotics can directly and/or indirectly affect the balance of the gut microbiome and, therefore, the clinical outcomes. In this article, we provided an overview of the composition of the gut microbiome under homeostasis and the mechanistic links between gut microbiota and colon cancer. The relationship between the use of oral antibiotics and colon cancer, as well as the impact of the gut microbiome on the efficacy and toxicities of chemotherapy in colon cancer, are discussed. Potential interventions to modulate microbiota and improve chemotherapy outcomes are discussed. Further studies are indicated to address these key gaps in the field and provide a scientific basis for the design of novel microbiota-based approaches for prevention/use as adjuvant therapeutics for patients with colon cancer.

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Gut Microbiota and Colon Cancer: A Role for Bacterial Protein Toxins?

Cited by 36 publications

References 183 publications

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

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

Impact of the Gut Microbiota Balance on the Health–Disease Relationship: The Importance of Consuming Probiotics and Prebiotics

Drug–Microbiota Interaction in Colon Cancer Therapy: Impact of Antibiotics

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