Alterations of circulating bacterial DNA in colorectal cancer and adenoma: A proof-of-concept study

Xiao, Qian; Lu, Wei; Kong, Xianglong; Shao, Yang; Hu, Yeting; Wang, Ao; Bao, Hua; Cao, Ran; Liu, Kaihua; Wang, Xiaonan; Wu, Xue; Zheng, Shu; Yuan, Ying; Ding, Kefeng

doi:10.1016/j.canlet.2020.11.030

Cited by 39 publications

(41 citation statements)

References 47 publications

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“…Colorectal cancer (CRC), also known as colorectal adenocarcinoma, is considered the second most leading cause of cancer-related mortality and is responsible for more than 1.3 million new cases per annum [ 1 , 2 ]. Such a growing rate of incidence makes it the most prevalent and significant health issue on a global scale.…”

Section: Introductionmentioning

confidence: 99%

“…In particular, Fusobacteria and Proteobacteria were more abundant in cancer specimens, whereas a significantly higher abundance of Fusobacteria and Firmicutes were observed in the stools of a colorectal patient [ 18 ]. According to recent studies, Peptosteptococcus , Clostridium , Prutella , Porphyromonas , and Bacteroides are the key bacteria linked with colorectal cancer [ 1 ]. Additionally, some other bacteria are currently considered to be linked with colorectal cancer, such as Streptococcus bovis , a Gram-positive opportunistic pathogen having the ability to grow in a 40% bile environment and cause systemic infections in the human body [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Colorectal Cancer Stage-Specific Fecal Bacterial Community Fingerprinting of the Taiwanese Population and Underpinning of Potential Taxonomic Biomarkers

et al. 2021

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Despite advances in the characterization of colorectal cancer (CRC), it still faces a poor prognosis. There is growing evidence that gut microbiota and their metabolites potentially contribute to the development of CRC. Thus, microbial dysbiosis and their metabolites associated with CRC, based on stool samples, may be used to advantage to provide an excellent opportunity to find possible biomarkers for the screening, early detection, prevention, and treatment of CRC. Using 16S rRNA amplicon sequencing coupled with statistical analysis, this study analyzed the cause–effect shift of the microbial taxa and their metabolites that was associated with the fecal gut microbiota of 17 healthy controls, 21 polyps patients, and 21 cancer patients. The microbial taxonomic shift analysis revealed striking differences among the healthy control, polyps and cancer groups. At the phylum level, Synergistetes was reduced significantly in the polyps group compared to the healthy control and cancer group. Additionally, at the genus level and in association with the cancer group, a total of 12 genera were highly enriched in abundance. In contrast, only Oscillosprira was significantly higher in abundance in the healthy control group. Comparisons of the polyps and cancer groups showed a total of 18 significantly enriched genera. Among them, 78% of the genera associated with the cancer group were in higher abundance, whereas the remaining genera showed a higher abundance in the polyps group. Additionally, the comparison of healthy control and polyp groups showed six significantly abundant genera. More than 66% of these genera showed a reduced abundance in the polyps group than in healthy controls, whereas the remaining genera were highly abundant in the polyps group. Based on tumor presence and absence, the abundance of Olsenella and Lactobacillus at the genus level was significantly reduced in the patient group compared to healthy controls. The significant microbial function prediction revealed an increase in the abundance of metabolites in the polyps and cancer groups compared to healthy controls. A correlation analysis revealed a higher contribution of Dorea in the predicted functions. This study showed dysbiosis of gut microbiota at the taxonomic level and their metabolic functions among healthy subjects and in two stages of colorectal cancer, including adenoma and adenocarcinoma, which might serve as potential biomarkers for the early diagnosis and treatment of CRC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Colorectal Cancer Stage-Specific Fecal Bacterial Community Fingerprinting of the Taiwanese Population and Underpinning of Potential Taxonomic Biomarkers

et al. 2021

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“…To our knowledge, no other study conducted an ad hoc data collection to systematically investigate blood microbiota in relation to CRC and/or IA to date. In a Chinese study, circulating bacterial DNA of 25 CRC, 10 IA and 22 healthy subjects was analysed through whole genome sequencing techniques on plasma samples [29], suggesting that the Flavobacterium DNA relative abundance was reduced in CRC and IA (<1%) as compared to control subjects (9.4%); on the contrary, there was a 10-fold increase DNA abundance of genus Ruminococcus in CRC (0.2%) as compared to controls (0.02%).…”

Section: Discussionmentioning

confidence: 99%

“…In particular, differences in circulating bacterial factors can occur in CRC patients, in whom epithelial barrier dysfunction can lead to increased intestinal permeability, plausibly resulting into a greater bacterial translocation from the gastrointestinal tract to bloodstream in IA and/or CRC. Some differences in relative abundance of the bacterial DNA in plasma between healthy, IA and CRC subjects have been reported in a case-control study from China, including 57 participants, but differences in terms of total bacterial load have not been analyzed yet [29].…”

Section: Introductionmentioning

confidence: 99%

Blood bacterial DNA, intestinal adenoma and colorectal cancer

Mutignani

Penagini

Gargari

et al. 2021

Preprint

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Objective We aimed to investigate the relation of blood bacterial DNA load and profiling with intestinal adenoma (IA) and colorectal cancer (CRC) patients. Design We performed 16S rRNA gene analysis of blood from 100 incident histologically confirmed CRC cases, 100 IA and 100 healthy subjects, matched to cases by centre, sex and age. Bacterial load was analysed using multiple conditional logistic regression. Differences in terms of abundance of bacteria between groups were estimated through analysis based on negative binomial distribution normalization. Random Forest was applied to predict the group assignment. Results We found an overrepresentation of blood 16S rRNA gene copies in colon cancer as compared to tumor-free controls (IA and healthy subjects). The odds ratio of colon cancer for the highest versus the lowest three quintiles of gene copies was 2.62. (95% confidence interval=1.22-5.65). No difference was found for rectal cancer and IA. For high 16S rRNA, community diversity was higher in colon cancers than controls. CRC cases had an enrichment of Peptostreptococcaceae and Acetobacteriaceae and a reduced abundance of Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae. Identified variables predicted CRC from control and IA patients with an accuracy of 0.70. Conclusion Colon cancer patients had a higher DNA bacterial load and a different bacterial profiling as compared to healthy subjects, IA and rectal cancers, indicating a higher passage of bacteria from gastrointestinal tract to bloodstream. Further studies are needed to confirm this result and exploit it to conceive new non-invasive techniques for an early diagnosis of CRC.

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Section: Introductionmentioning

confidence: 99%

Blood Bacterial DNA Load and Profiling Differ in Colorectal Cancer Patients Compared to Tumor-Free Controls

Mutignani¹,

Penagini

Gargari

et al. 2021

Cancers

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Inflammation and immunity are linked to intestinal adenoma (IA) and colorectal cancer (CRC) development. The gut microbiota is associated with CRC risk. Epithelial barrier dysfunction can occur, possibly leading to increased intestinal permeability in CRC patients. We conducted a case-control study including 100 incident histologically confirmed CRC cases, and 100 IA and 100 healthy subjects, matched to cases by center, sex and age. We performed 16S rRNA gene analysis of blood and applied conditional logistic regression. Further analyses were based on negative binomial distribution normalization and Random Forest algorithm. We found an overrepresentation of blood 16S rRNA gene copies in colon cancer as compared to tumor-free controls. For high levels of gene copies, community diversity was higher in colon cancer cases than controls. Bacterial taxa and operational taxonomic unit abundances were different between groups and were able to predict CRC with an accuracy of 0.70. Our data support the hypothesis of a higher passage of bacteria from gastrointestinal tract to bloodstream in colon cancer. This result can be applied on non-invasive diagnostic tests for colon cancer control.

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Alterations of circulating bacterial DNA in colorectal cancer and adenoma: A proof-of-concept study

Cited by 39 publications

References 47 publications

Colorectal Cancer Stage-Specific Fecal Bacterial Community Fingerprinting of the Taiwanese Population and Underpinning of Potential Taxonomic Biomarkers

Colorectal Cancer Stage-Specific Fecal Bacterial Community Fingerprinting of the Taiwanese Population and Underpinning of Potential Taxonomic Biomarkers

Blood bacterial DNA, intestinal adenoma and colorectal cancer

Blood Bacterial DNA Load and Profiling Differ in Colorectal Cancer Patients Compared to Tumor-Free Controls

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