Targeting colorectal cancer-associated bacteria: A new area of research for personalized treatments

Faïs, Tiphanie; Delmas, Julien; Cougnoux, Antony; Dalmasso, Guillaume; Bonnet, Richard

doi:10.1080/19490976.2016.1155020

Cited by 20 publications

(16 citation statements)

References 35 publications

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“…In many existing studies, there are also other bacteria to be proved to play an indispensable role across stages of colorectal carcinogenesis, including Butyricicoccus, E. coli [25,35], Parvimonas micra and Solobacterium moorei [26], Bacteroides fragilis [27,36], Parvimonas micra and Peptostreptococcus [28,37], Prevotella [38], Campylobacter jejuni [3], Faecalibacterium prausnitzii, Bifidobacterium, and lactobacillus genus [31]. Another unique feature of our study is that animal experiments are used to confirm that microflora changes indeed promote the occurrence and development of CRC.…”

Section: Discussionmentioning

confidence: 99%

Study of the Relationship between Microbiome and Colorectal Cancer Susceptibility Using 16SrRNA Sequencing

Liu

Zhang

Shu

et al. 2020

BioMed Research International

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A lot of previous studies have recently reported that the gut microbiota influences the development of colorectal cancer (CRC) in Western countries, but the role of the gut microbiota in Chinese population must be investigated fully. The goal of this study was to determine the role of the gut microbiome in the initiation and development of CRC. We collected fecal samples of 206 Chinese individuals: 59 with polyp (group P), 54 with adenoma (group A), 51 with colorectal cancer (group CC), and 42 healthy controls (group HC).16S ribosomal RNA (rRNA) was used to compare the microbiota community structures among healthy controls, patients with polyp, and those with adenoma or colorectal cancer. Our study proved that intestinal flora, as a specific indicator, showed significant differences in its diversity and composition. Sobs, Chao, and Ace indexes of group CC were significantly lower than those of the healthy control group (CC group: Sobs, Chao, and Ace indexes were 217.3 ± 69, 4265.1 ± 80.7, and 268.6 ± 78.1, respectively; HC group: Sobs, Chao, and Ace indexes were 228.8 ± 44.4, 272.9 ± 58.6, and 271.9 ± 57.2, respectively). When compared with the healthy individuals, the species richness and diversity of intestinal flora in patients with colorectal cancer were significantly reduced: PCA and PCoA both revealed that a significant separation in bacterial community composition between the CC group and HC group (with PCA using the first two principal component scores of PC1 14.73% and PC2 10.34% of the explained variance, respectively; PCoA : PC1 = 14%, PC2 = 9%, PC3 = 6%). Wilcox tests was used to analyze differences between the two groups, it reveals that Firmicutes (P=0.000356), Fusobacteria (P=0.000001), Proteobacteria (P=0.000796), Spirochaetes (P=0.013421), Synergistetes (P=0.005642) were phyla with significantly different distributions between cases and controls. The proportion of microorganism composition is varying at different stages of colon cancer development: Bacteroidetes (52.14%) and Firmicutes (35.88%) were enriched in the healthy individuals; on the phylum level, the abundance of Bacteroidetes (52.14%-53.92%-52.46%–47.06%) and Firmicutes (35.88%-29.73%-24.27%–25.36%) is decreasing with the development of health-polyp-adenomas-CRC, and the abundance of Proteobacteria (9.33%-12.31%-16.51%–22.37%) is increasing. PCA and PCOA analysis showed there was no significant (P<0.05) difference in species similarity between precancerous and carcinogenic states. However, the composition of the microflora in patients with precancerous lesions (including patients with adenoma and polyp) was proved to have no significant disparity (P<0.05). Our study provides insights into new angles to dig out potential biomarkers in diagnosis and treatment of colorectal cancer and to provide scientific advice for a healthy lifestyle for the sake of gut microbiota.

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Section: Discussionmentioning

confidence: 99%

Study of the Relationship between Microbiome and Colorectal Cancer Susceptibility Using 16SrRNA Sequencing

Liu

Zhang

Shu

et al. 2020

BioMed Research International

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“…Thus, inhibition of crucial proteins (Clbs) involved in colibactin synthesis has been proposed [ 45 , 67 ], and inhibitors targeting ClbP have been developed [ 67 ]. Interestingly, these molecules were able to abolish colibactin-induced DNA damage both in vitro and in a CRC mouse model, and as a result, decreased the number of tumours [ 67 , 83 ]. This proof of concept suggests that personalized medicine in the future should consider not only the genetics of the tumour but also the tumour-associated bacteria.…”

Section: Roles Of Colibactinmentioning

confidence: 99%

Colibactin: More Than a New Bacterial Toxin

Faïs

Delmas

Barnich

et al. 2018

Toxins

171

177

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Cyclomodulins are bacterial toxins that interfere with the eukaryotic cell cycle. A new cyclomodulin called colibactin, which is synthetized by the pks genomic island, was discovered in 2006. Despite many efforts, colibactin has not yet been purified, and its structure remains elusive. Interestingly, the pks island is found in members of the family Enterobacteriaceae (mainly Escherichia coli and Klebsiella pneumoniae) isolated from different origins, including from intestinal microbiota, septicaemia, newborn meningitis, and urinary tract infections. Colibactin-producing bacteria induce chromosomal instability and DNA damage in eukaryotic cells, which leads to senescence of epithelial cells and apoptosis of immune cells. The pks island is mainly observed in B2 phylogroup E. coli strains, which include extra-intestinal pathogenic E. coli strains, and pks E. coli are over-represented in biopsies isolated from colorectal cancer. In addition, pks E. coli bacteria increase the number of tumours in diverse colorectal cancer mouse models. Thus, colibactin could have a major impact on human health. In the present review, we will focus on the biological effects of colibactin, the distribution of the pks island, and summarize what is currently known about its synthesis and its structure.

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“…Some toxins can cause DNA damage, and then affect the cell cycle. E. coli harboring cytotoxic necrotizing factor (CNF) and cytolethal distending toxin (CDT) are particularly associated with CRC biopsies . In addition, DNA mismatch repair (MMR) plays a key role in sustaining genomic stability, which is a highly conserved biological pathway.…”

Section: Typical Microbial Families Contributing To Colorectal Cancermentioning

confidence: 99%

“…E. coli harboring cytotoxic necrotizing factor (CNF) and cytolethal distending toxin (CDT) are particularly associated with CRC biopsies. 71 In addition, DNA mismatch repair (MMR) plays a key role in sustaining genomic stability, 72 which is a highly conserved biological pathway. MMR acts in the DNA damage response pathway, which degrades severely damaged cells and prevents both short-term mutagenesis and long-term tumorigenesis.…”

Section: Escherichia Colimentioning

confidence: 99%

The role of microbiota in the development of colorectal cancer

Dai

Zhang

et al. 2019

Intl Journal of Cancer

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Colorectal cancer is the third largest cancer in worldwide and has been proven to be closely related to the intestinal microbiota. Many reports and clinical studies have shown that intestinal microbial behavior may lead to pathological changes in the host intestines. The changes can be divided into epigenetic changes and carcinogenic changes at the gene level, which ultimately promote the production and development of colorectal cancer. This article reviews the pathways of microbial signaling in the intestinal epithelial barrier, the role of microbiota in inflammatory colorectal tumors, and typical microbial carcinogenesis. Finally, by gaining a deeper understanding of the intestinal microbiota, we hope to achieve the goal of treating colorectal cancer using current microbiota technologies, such as fecal microbiological transplantation.

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Targeting colorectal cancer-associated bacteria: A new area of research for personalized treatments

Cited by 20 publications

References 35 publications

Study of the Relationship between Microbiome and Colorectal Cancer Susceptibility Using 16SrRNA Sequencing

Study of the Relationship between Microbiome and Colorectal Cancer Susceptibility Using 16SrRNA Sequencing

Colibactin: More Than a New Bacterial Toxin

The role of microbiota in the development of colorectal cancer

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