scholarly journals 16S rRNA of Mucosal Colon Microbiome and CCL2 Circulating Levels Are Potential Biomarkers in Colorectal Cancer

2021 ◽  
Vol 22 (19) ◽  
pp. 10747
Author(s):  
Carmela Nardelli ◽  
Ilaria Granata ◽  
Marcella Nunziato ◽  
Mario Setaro ◽  
Fortunata Carbone ◽  
...  

Colorectal cancer (CRC) is one of the most common malignancies in the Western world and intestinal dysbiosis might contribute to its pathogenesis. The mucosal colon microbiome and C-C motif chemokine 2 (CCL2) were investigated in 20 healthy controls (HC) and 20 CRC patients using 16S rRNA sequencing and immunoluminescent assay, respectively. A total of 10 HC subjects were classified as overweight/obese (OW/OB_HC) and 10 subjects were normal weight (NW_HC); 15 CRC patients were classified as OW/OB_CRC and 5 patients were NW_CRC. Results: Fusobacterium nucleatum and Escherichia coli were more abundant in OW/OB_HC than in NW_HC microbiomes. Globally, Streptococcus intermedius, Gemella haemolysans, Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were significantly increased in CRC patient tumor/lesioned tissue (CRC_LT) and CRC patient unlesioned tissue (CRC_ULT) microbiomes compared to HC microbiomes. CCL2 circulating levels were associated with tumor presence and with the abundance of Fusobacterium nucleatum, Bacteroides fragilis and Gemella haemolysans. Our data suggest that mucosal colon dysbiosis might contribute to CRC pathogenesis by inducing inflammation. Notably, Fusobacterium nucleatum, which was more abundant in the OW/OB_HC than in the NW_HC microbiomes, might represent a putative link between obesity and increased CRC risk.

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Marco Antonio Hernández-Luna ◽  
Sergio López-Briones ◽  
Rosendo Luria-Pérez

Worldwide, neoplasms of the gastrointestinal tract have a very high incidence and mortality. Among these, colorectal cancer, which includes colon and rectum malignancies, representing both highest incidence and mortality. While gallbladder cancer, another neoplasm associated to gastrointestinal tract occurs less frequently. Genetic factors, inflammation and nutrition are important risk factors associated with colorectal cancer development. Likewise, pathogenic microorganisms inducing intestinal dysbiosis have become an important scope to determine the role of bacterial infection on tumorigenesis. Interestingly, in human biopsies of different types of gastrointestinal tract cancer, the presence of different bacterial strains, such as Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis and Salmonella enterica have been detected, and it has been considered as a high-risk factor to cancer development. Therefore, pathogens infection could contribute to neoplastic development through different mechanisms; including intestinal dysbiosis, inflammation, evasion of tumoral immune response and activation of pro-tumoral signaling pathways, such as β catenin. Here, we have reviewed the suggested bacterial molecular mechanisms and their possible role on development and progression of gastrointestinal neoplasms, focusing mainly on colon neoplasms, where the bacteria Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis and Salmonella enterica infect.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Aref Shariati ◽  
Shabnam Razavi ◽  
Ehsanollah Ghaznavi-Rad ◽  
Behnaz Jahanbin ◽  
Abolfazl Akbari ◽  
...  

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.


2020 ◽  
Vol 11 ◽  
Author(s):  
Yiwen Cheng ◽  
Zongxin Ling ◽  
Lanjuan Li

The intestinal microbiota, composed of a large population of microorganisms, is often considered a “forgotten organ” in human health and diseases. Increasing evidence indicates that dysbiosis of the intestinal microbiota is closely related to colorectal cancer (CRC). The roles for intestinal microorganisms that initiated and facilitated the CRC process are becoming increasingly clear. Hypothesis models have been proposed to illustrate the complex relationship between the intestinal microbiota and CRC. Recent studies have identified Streptococcus bovis, enterotoxigenic Bacteroides fragilis, Fusobacterium nucleatum, Enterococcus faecalis, Escherichia coli, and Peptostreptococcus anaerobius as CRC candidate pathogens. In this review, we summarized the mechanisms involved in microbiota-related colorectal carcinogenesis, including inflammation, pathogenic bacteria, and their virulence factors, genotoxins, oxidative stress, bacterial metabolites, and biofilm. We also described the clinical values of intestinal microbiota and novel strategies for preventing and treating CRC.


2021 ◽  
Author(s):  
Liying Zhang ◽  
Jiaqi Zhu ◽  
Qiutao Ding ◽  
Yanqi Huang ◽  
Hongbo Zhang ◽  
...  

Abstract The association between the gut microbiome and the five stages of colorectal cancer (CRC) (healthy, polyposis, nonadvanced adenoma, advanced adenoma, and cancer) remains unclear. We performed 16S rRNA sequencing of the V3-V4 amplicon from 999 samples from subjects at various stages of CRC development and constructed an accurate predictive random forest model for CRC development. In the testing set, our five-category CRC prediction classifier had accuracies of 0.84 and 0.74 using the relative operational taxonomic unit (OTU) abundances and relative genus abundances, respectively. Specifically, the OTU-based classifier had a sensitivity of 0.97 and specificity of 0.97 for CRC samples, and the genus-based classifier had a sensitivity of 0.97 and specificity of 0.95 for CRC samples. Meanwhile, the gut microbiota was found to differ at all stages of CRC development. The differential abundances of closely related bacteria were used to accurately classify the five stages of CRC development. Additionally, both unannotated and annotated OTUs played important roles in classifier modelling. Our work not only provides valuable 16S rRNA sequencing data from patients and healthy individuals on a large scale but also identifies reproducible gut microbiome biomarkers for CRC staging and highlights their potential applications as noninvasive microbiome biomarkers for diagnosis and as predictive CRC screening tests.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Kaixi Liu ◽  
Xinran Yang ◽  
Mi Zeng ◽  
Yumeng Yuan ◽  
Jianhong Sun ◽  
...  

Background. Accurate analysis of intestinal microbiota will facilitate establishment of an evaluating system for assessing colorectal cancer (CRC) risk and prognosis. This study evaluates the potential role of Fusobacterium nucleatum (F. nucleatum) and Escherichia coli with a pks gene (pks+ E. coli) in early CRC diagnosis. Methods. We recruited 139 patients, including CRC ( n = 60 ), colorectal adenomatous polyposis (CAP) ( n = 37 ), and healthy individuals ( n = 42 ) based on their colonoscopy examinations. We collected stool and serum samples from the participants and measured the relative abundance of F. nucleatum and pks+ E. coli in fecal samples by quantitative PCR. Receiver operating characteristic curve (ROC) analyses were used to analyze the diagnostic value of single or combined biomarkers. Results. Fecal F. nucleatum and pks+ E. coli levels were higher in the CRC group in either the CAP group or healthy controls ( P = 0.02 ; 0.01). There was no statistical difference in the distribution of F. nucleatum and pks+ E. coli in patients with different tumor sites ( P > 0.05 ). The combination of F. nucleatum+pks+ E. coli+CEA+CA19-9+FOBT was chosen as the optimal panel in differentiating both CRC and CAP from the controls. The combination of F. nucleatum, pks+ E. coli, and FOBT improved diagnostic efficiency. However, there was difficulty in differentiating CRC from CAP. Conclusion. Our results suggested that combining bacterial markers with conventional tumor markers improves the diagnostic efficiency for noninvasive diagnosis of CRC.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Sukjung Choi ◽  
Jongsuk Chung ◽  
Mi-La Cho ◽  
Donghyun Park ◽  
Sun Shim Choi

Abstract Background Comparing the microbiome compositions obtained under different physiological conditions has frequently been attempted in recent years to understand the functional influence of microbiomes in the occurrence of various human diseases. Methods In the present work, we analyzed 102 microbiome datasets containing tumor- and normal tissue-derived microbiomes obtained from a total of 51 Korean colorectal cancer (CRC) patients using 16S rRNA amplicon sequencing. Two types of comparisons were used: ‘normal versus (vs.) tumor’ comparison and ‘recurrent vs. nonrecurrent’ comparison, for which the prognosis of patients was retrospectively determined. Results As a result, we observed that in the ‘normal vs. tumor’ comparison, three phyla, Firmicutes, Actinobacteria, and Bacteroidetes, were more abundant in normal tissues, whereas some pathogenic bacteria, including Fusobacterium nucleatum and Bacteroides fragilis, were more abundant in tumor tissues. We also found that bacteria with metabolic pathways related to the production of bacterial motility proteins or bile acid secretion were more enriched in tumor tissues. In addition, the amount of these two pathogenic bacteria was positively correlated with the expression levels of host genes involved in the cell cycle and cell proliferation, confirming the association of microbiomes with tumorigenic pathway genes in the host. Surprisingly, in the ‘recurrent vs. nonrecurrent’ comparison, we observed that these two pathogenic bacteria were more abundant in the patients without recurrence than in the patients with recurrence. The same conclusion was drawn in the analysis of both normal and tumor-derived microbiomes. Conclusions Taken together, it seems that understanding the composition of tissue microbiomes is useful for predicting the prognosis of CRC patients.


2017 ◽  
Vol 15 (3) ◽  
pp. 353-359
Author(s):  
Andrée F. Maheux ◽  
Sébastien Bouchard ◽  
Ève Bérubé ◽  
Michel G. Bergeron

The MI, Chromocult® coliform, and Compass CC chromogenic culture-based methods used to assess water quality by the detection of Escherichia coli and total coliforms were compared in terms of their specificity and sensitivity, using 16S rRNA sequencing for colony identification. A sewage water sample was divided in 2-μL subsamples for testing by all three culture-based methods. All growing colonies were harvested and subjected to 16S rRNA sequencing. Test results showed that all E. coli colonies were correctly identified by all three methods, for a specificity and a sensitivity of 100%. However, for the total coliform detection, the MI agar, Chromocult® coliform agar, and Compass CC agar were specific for only 69.2% (9/13), 47.2% (25/53), and 40.5% (17/42), whereas sensitive for 97.8% (45/46), 97.5% (39/40), and 85.7% (24/28), respectively. Thus, given the low level of specificity of these methods for the detection of total coliforms, confirming the identity of total coliform colonies could help to take public health decisions, in particular for cities connected to a public drinking water distribution system since the growth of few putative total coliform colonies on chromogenic agar is problematic and can lead to unnecessary and costly boiling notices from public health authorities.


Gut Microbes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 1-14
Author(s):  
Julia Butt ◽  
Mazda Jenab ◽  
Jill Werner ◽  
Veronika Fedirko ◽  
Elisabete Weiderpass ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Myungsook Kim ◽  
Seung-Tae Lee ◽  
Songyi Choi ◽  
Hyukmin Lee ◽  
Sun Sung Kwon ◽  
...  

AbstractThe roles of individual bacteria and their relationship in the development of colorectal cancer (CRC) remain unclear. We aimed to determine the prevalence of CRC-associated bacteria using quantitative real-time PCR (qPCR) or 16S rRNA analysis and the statistical correlations of patient demographics and clinical characteristics comprising alcohol consumption with CRC-associated bacteria. We determined the prevalence of five CRC-associated bacterial species in 38 CRC patients (39 samples) and 21 normal individuals using qPCR, and the relative abundance of bacterial taxa in the gut microbiome was assessed using 16S rRNA analysis. Fusobacterium nucleatum was the only bacterium that was significantly (P < 0.0001) more prevalent in the cancer tissue (82.1%) than in the normal tissue (0%) by qPCR. 16S rRNA analysis showed a significant correlation between six operational taxonomic units (OTUs), namely, the genera Fusobacterium, Peptostreptococcus, Collinsella, Prevotella, Parvimonas, and Gemella, in patients with CRC. An integrated analysis using 16S rRNA data and epidemiological characteristics showed that alcohol consumption was significantly correlated with the abundance of Fusobacterium OTUs. The correlation of alcohol consumption with the abundance of Fusobacterium OTUs in cancer tissue discovered using 16S rRNA analysis suggests a possible link between alcohol metabolism and subsequent tumorigenesis caused by F. nucleatum.


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