scholarly journals Alterations, Interactions, and Diagnostic Potential of Gut Bacteria and Viruses in Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Renyuan Gao ◽  
Yefei Zhu ◽  
Cheng Kong ◽  
Kai Xia ◽  
Hao Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
Fusobacterium Nucleatum ◽  
Gut Bacteria ◽  
Microbial Interactions ◽  
Diagnostic Model ◽  
Metagenomic Sequencing ◽  
Diagnostic Potential ◽  
Diagnostic Panel

Gut microbiome alteration was closely associated with colorectal cancer (CRC). Previous studies had demonstrated the bacteria composition changes but lacked virome profiles, trans-kindom interactions, and reliable diagnostic model explorations in CRC. Hence, we performed metagenomic sequencing to investigate the gut microbiome and microbial interactions in adenoma and CRC patients. We found the decreased microbial diversity in CRC and revealed the taxonomic alterations of bacteria and viruses were highly associated with CRC at the species level. The relative abundance of oral-derived species, such as Fusobacterium nucleatum, Fusobacterium hwasookii, Porphyromonas gingivalis, and Bacteroides fragilis, increased. At the same time, butyrate-producing and anti-inflammatory microbes decreased in adenoma and CRC by non-parametric Kruskal-Wallis test. Despite that, the relative abundance of Escherichia viruses and Salmonella viruses increased, whereas some phages, including Enterobacteria phages and Uncultured crAssphage, decreased along with CRC development. Gut bacteria was negatively associated with viruses in CRC and healthy control by correlation analysis (P=0.017 and 0.002, respectively). Viruses were much more dynamic than the bacteria as the disease progressed, and the altered microbial interactions were distinctively stage-dependent. The degree centrality of microbial interactions decreased while closeness centrality increased along with the adenoma to cancer development. Uncultured crAssphage was the key bacteriophage that enriched in healthy controls and positively associated with butyrate-producing bacteria. Diagnostic tests based on bacteria by random forest confirmed in independent cohorts showed better performance than viruses for CRC. In conclusion, our study revealed the novel CRC-associated bacteria and viruses that exhibited specific differences and intensive microbial correlations, which provided a reliable diagnostic panel for CRC.

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

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Aref Shariati ◽  
Shabnam Razavi ◽  
Ehsanollah Ghaznavi-Rad ◽  
Behnaz Jahanbin ◽  
Abolfazl Akbari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Relative Abundance ◽  
Normal Tissue ◽  
Bacteroides Fragilis ◽  
Fusobacterium Nucleatum ◽  
Normal Mucosa ◽  
Clinicopathologic Characteristics ◽  
Tissue Samples ◽  
Adjacent Normal Mucosa ◽  
Iranian Patients

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.

scholarly journals The Infant Gut Resistome is Associated with E. coli and Early-life Exposures

2020 ◽  
Author(s):  
Rebecca M. Lebeaux ◽  
Modupe O. Coker ◽  
Erika F. Dade ◽  
Thomas J. Palys ◽  
Hilary G. Morrison ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Relative Risk ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
Early Life ◽  
The United States ◽  
Delivery Mode ◽  
Metagenomic Sequencing ◽  
E Coli ◽  
Early Life Exposures

Abstract Background: Antibiotic resistance is an increasing threat to human health. The human gut microbiome harbors a collection of bacterial antimicrobial resistance genes (ARGs) known as the resistome. The factors associated with establishment of the resistome in early life are not well understood and clarifying these factors would inform strategies to decrease antibiotic resistance. We investigated the early-life exposures and taxonomic signatures associated with resistome development over the first year of life in a large, prospective cohort in the United States. Shotgun metagenomic sequencing was used to profile both microbial composition and ARGs in stool samples collected at 6 weeks and 1 year of age from infants enrolled in the New Hampshire Birth Cohort Study. Negative binomial regression and statistical modeling was used to examine infant factors such as sex, delivery mode, feeding method, gestational age, antibiotic exposure, and infant gut microbiome composition in relation to the diversity and relative abundance of ARGs.Results: Metagenomic sequencing was performed on paired samples from 195 full term (at least 37 weeks’ gestation) and 15 late preterm (33-36 weeks’ gestation) infants. 6-week samples compared to 1-year samples had 4.37 times (95% CI: 3.54-5.39) the rate of harboring ARGs. The majority of ARGs that were at a greater relative abundance at 6 weeks (chi-squared p < 0.01) worked through the mechanism of antibiotic efflux (i.e., by pumping antibiotics out of the cell). The overall relative abundance of the resistome was strongly correlated with Proteobacteria (Spearman correlation = 78.9%) and specifically E. coli (62.2%) relative abundance in the gut microbiome. Among infant characteristics, delivery mode was most strongly associated with the diversity and relative abundance of ARGs. Infants born via cesarean delivery had a higher risk of harboring unique ARGs [relative risk = 1.12 (95% CI: 0.97 – 1.29)] as well as a having an increased risk for overall ARG relative abundance [relative risk = 1.43 (95% CI: 1.12 – 1.84)] at 1 year compared to infants born vaginally. Additionally, 6 specific ARGs were at a greater relative abundance in infants delivered by cesarean section compared to vaginally delivered infants across both time points. Conclusions: Our findings suggest that the developing infant gut resistome may be alterable by early-life exposures. Establishing the extent to which infant characteristics and early-life exposures impact the resistome can ultimately lead to interventions that decrease the transmission of ARGs and thus the possibility of antibiotic resistant life threatening infections.

scholarly journals Weaning age and its effect on the development of the swine gut microbiome and resistome

2021 ◽  
Author(s):  
Devin B Holman ◽  
Katherine E Gzyl ◽  
Kathy T Mou ◽  
Heather K Allen
Keyword(s):  
Relative Abundance ◽  
Gut Microbiome ◽  
Rrna Gene ◽  
Metagenomic Sequencing ◽  
Carbohydrate Active Enzymes ◽  
Fecal Microbiome ◽  
Shotgun Metagenomic Sequencing ◽  
Swine Operations ◽  
Weaning Age

Piglets are often weaned between 19 and 22 d of age in North America although in some swine operations this may occur at 14 d or less. Piglets are abruptly separated from their sow at weaning and are quickly transitioned from sow's milk to a plant-based diet. The effect of weaning age on the long-term development of the pig gut microbiome is largely unknown. In this study, pigs were weaned at either 14, 21, or 28 d of age and fecal samples collected 21 times from d 4 (neonatal) through to marketing at d 140. The fecal microbiome was characterized using 16S rRNA gene and shotgun metagenomic sequencing. The fecal microbiome of all piglets shifted significantly three to seven days post-weaning with an increase in microbial diversity. Several Prevotella spp. increased in relative abundance immediately after weaning as did butyrate-producing species such as Butyricicoccus porcorum, Faecalibacterium prausnitzii, and Megasphaera elsdenii. Within 7 days of weaning, the gut microbiome of pigs weaned at 21 and 28 days of age resembled that of pigs weaned at 14 d. Resistance genes to most antimicrobial classes decreased in relative abundance post-weaning with the exception of those conferring resistance to tetracyclines and macrolides-lincosamides-streptogramin B. The relative abundance of microbial carbohydrate-active enzymes (CAZymes) changed significantly in the post-weaning period with an enrichment of CAZymes involved in degradation of plant-derived polysaccharides. These results demonstrate that pigs tend to have a more similar microbiome as they age and that weaning age has only a temporary effect on the gut microbiome.

scholarly journals The gut microbiome and potential implications for early-onset colorectal cancer

2020 ◽  
Vol 9 (3) ◽  
pp. CRC25
Author(s):  
Reetu Mukherji ◽  
Benjamin A Weinberg
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiome ◽  
Early Onset ◽  
Older Patients ◽  
Fusobacterium Nucleatum ◽  
Distal Colon ◽  
Gastrointestinal Cancers ◽  
Human Gut ◽  
Colon And Rectal Cancer ◽  
Early Onset Colorectal Cancer

Recently, there has been an unexpected trend toward increased incidence of colorectal cancer in younger individuals, particularly distal colon and rectal cancer in those under age 50. There is evidence to suggest that the human gut microbiome may play a role in carcinogenesis. The microbiome is dynamic and varies with age, geography, ethnicity and diet. Certain bacteria such as Fusobacterium nucleatum have been implicated in the development of colorectal and other gastrointestinal cancers. Recent data suggest that bacteria can alter the inflammatory and immune environment, influencing carcinogenesis, lack of treatment response and prognosis. Studies to date focus on older patients. Because the microbiome varies with age, it could be a potential explanation for the rise in early-onset colorectal cancer.

scholarly journals Emerging Evidence on the Effects of Dietary Factors on the Gut Microbiome in Colorectal Cancer

2021 ◽  
Author(s):  
Sandeep Appunni ◽  
Muni Rubens ◽  
Venkataraghavan Ramamoorthy ◽  
Anshul Saxena ◽  
Raees Tonse ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiome ◽  
Colonic Mucosa ◽  
Fusobacterium Nucleatum ◽  
Dietary Factors ◽  
Lifestyle Modifications ◽  
Related Factors ◽  
Molecular Events ◽  
Relationship Of ◽  
The Relationship

Dietary factors play an important role in shaping the gut microbiome which, in turn, regulates the molecular events in colonic mucosa. The composition and resulting metabolism of the gut microbiome have been implicated in the development of colorectal cancer (CRC). Diets low in dietary fibers and phytomolecules as well as other lifestyle-related factors may predispose to CRC. Emerging evidence demonstrates that the predominance of microbes, such as Fusobacterium nucleatum, can predispose the colonic mucosa to malignant transformation. Dietary and lifestyle modifications have been demonstrated to restrict the growth of potentially harmful opportunistic organisms. In this study, we aim to present evidence regarding the relationship of dietary factors to the gut microbiome and development of CRC.

scholarly journals Growth rate alterations of human colorectal cancer cells by 157 gut bacteria

2019 ◽  
Author(s):  
Rahwa Taddese ◽  
Daniel R. Garza ◽  
Lilian N. Ruiter ◽  
Marien I. de Jonge ◽  
Clara Belzer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Human Cancer ◽  
Gut Bacteria ◽  
Bacterial Cells ◽  
Bacterial Strains

ABSTRACTSeveral bacteria in the human gut microbiome have been associated with colorectal cancer (CRC) by high-throughput screens. In some cases, molecular mechanisms have been elucidated that drive tumorigenesis, including bacterial membrane proteins or secreted molecules that interact with the human cancer cells. For most gut bacteria, however, it remains unknown if they enhance or inhibit cancer cell growth. Here, we screened bacteria-free supernatants (secretomes) and inactivated cells of over 150 cultured bacterial strains for their effect on CRC cell growth. We observed family-level and strain-level effects that often differed between bacterial cells and secretomes, suggesting that different molecular mechanisms are at play. Secretomes of Bacteroidaceae, Enterobacteriaceae, and Erysipelotrichaceae bacteria enhanced CRC cell growth, while most Fusobacteriaceae cells and secretomes inhibited growth, contrasting prior findings. In some bacteria, the presence of specific functional genes was associated with CRC cell growth rates, including the virulence genes TcdA in Clostridiales and FadA in Fusobacteriaceae, which both inhibited growth. Bacteroidaceae cells that enhanced growth were enriched for genes of the cobalamin synthesis pathway, while Fusobacteriaceae cells that inhibit growth were enriched for genes of the ethanolamine utilization pathway. Together, our results reveal how different gut bacteria have wide-ranging effects on cancer cells, contribute a better understanding of the effects of the gut microbiome on the human host, and provide a valuable resource for identifying candidate target genes for potential microbiome-based diagnostics and treatment strategies.

scholarly journals The Diagnostic Potential & Interactive Dynamics of the Colorectal Cancer Virome

2017 ◽  
Author(s):  
Geoffrey D Hannigan ◽  
Melissa B Duhaime ◽  
Mack T Ruffin ◽  
Charlie C Koumpouras ◽  
Patrick D Schloss
Keyword(s):  
Colorectal Cancer ◽  
Bacterial Community ◽  
Cancer Progression ◽  
Bacterial Community Composition ◽  
Rrna Gene ◽  
Metagenomic Sequencing ◽  
Diagnostic Potential ◽  
Forest Modeling ◽  
Human Viruses ◽  
Virus Community

AbstractHuman viruses (those that infect human cells) have been associated with many cancers, largely due to their mutagenic and functionally manipulative abilities. Despite this, cancer microbiome studies have almost exclusively focused on bacteria instead of viruses. We began evaluating the cancer virome by focusing on colorectal cancer, a primary cause of morbidity and mortality throughout the world, and a cancer linked to altered colonic bacterial community compositions but with an unknown association with the gut virome. We used 16S rRNA gene, whole shotgun metagenomic, and purified virus metagenomic sequencing of stool to evaluate the differences in human colorectal cancer virus and bacterial community composition. Through random forest modeling we identified differences in the healthy and colorectal cancer virome. The cancer-associated virome consisted primarily of temperate bacteriophages that were also predicted to be bacteria-virus community network hubs. These results provide foundational evidence that bacteriophage communities are associated with colorectal cancer and potentially impact cancer progression by altering the bacterial host communities.

scholarly journals Comprehensive Analysis of a tRNA-Derived Small RNA in Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yong Zhu ◽  
Shaoqiu Chen ◽  
Zhougui Ling ◽  
Andrew Winnicki ◽  
Lilly Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Small Rna ◽  
Interaction Network ◽  
Diagnostic Methods ◽  
Cancer Prognosis ◽  
Diagnostic Model ◽  
Tissue Samples ◽  
Mrna Targets ◽  
Diagnostic Panel ◽  
New Biomarkers

Colorectal cancer often presents as a highly variable disease with myriad forms that are at times difficult to detect in early screenings with sufficient accuracy, for which novel diagnostic methods are an attractive and valuable area of improvement. To improve colorectal cancer diagnosis and prognosis, new biomarkers that can be assembled into a diagnostic panel must be identified, and tRNA-derived small RNAs (tsRNAs) are a particularly interesting and increasingly visible new class of molecules to examine. In this study, small RNA-seq data were profiled for the expression of 104 human tsRNAs in tumor tissue and adjacent normal tissue samples, and a diagnostic model was built based on four differentially expressed tsRNAs: tRF-22-WB86Q3P92, tRF-22-WE8SPOX52, tRF-22-WE8S68L52, tRF-18-8R1546D2. Furthermore, the diagnostic model was validated by two independent validation datasets (AUC was 0.97 and 0.99), and a LASSO model was applied to develop a seven-tsRNA-based risk score model for colorectal cancer prognosis. Finally, a tsRNA-mRNA interaction network was established according to potential mRNA targets predicted by bioinformatic methods. In conclusion, the results suggest that abnormal expression of tsRNA in colorectal cancer may have a functional effect on tumor action and moreover, that some of the tsRNAs identified in this study with diagnostic and prognostic potential could be of clinical significance.

scholarly journals Diagnostic Potential and Interactive Dynamics of the Colorectal Cancer Virome

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Geoffrey D. Hannigan ◽  
Melissa B. Duhaime ◽  
Mack T. Ruffin ◽  
Charlie C. Koumpouras ◽  
Patrick D. Schloss
Keyword(s):  
Colorectal Cancer ◽  
Bacterial Community ◽  
Community Composition ◽  
Cancer Progression ◽  
Bacterial Community Composition ◽  
The United States ◽  
Rrna Gene ◽  
Metagenomic Sequencing ◽  
Diagnostic Potential ◽  
Virus Communities

ABSTRACT Human viruses (those that infect human cells) have been associated with many cancers, largely due to their mutagenic and functionally manipulative abilities. Despite this, cancer microbiome studies have focused almost exclusively on bacteria instead of viruses. We began evaluating the cancer virome by focusing on colorectal cancer, a primary cause of morbidity and mortality throughout the world and a cancer linked to altered colonic bacterial community compositions but with an unknown association with the gut virome. We used 16S rRNA gene, whole shotgun metagenomic, and purified virus metagenomic sequencing of stool to evaluate the differences in human colorectal cancer virus and bacterial community composition. Through random forest modeling, we identified differences in the healthy and colorectal cancer viromes. The cancer-associated virome consisted primarily of temperate bacteriophages that were also predicted to be bacterium-virus community network hubs. These results provide foundational evidence that bacteriophage communities are associated with colorectal cancer and potentially impact cancer progression by altering the bacterial host communities. IMPORTANCE Colorectal cancer is a leading cause of cancer-related death in the United States and worldwide. Its risk and severity have been linked to colonic bacterial community composition. Although human-specific viruses have been linked to other cancers and diseases, little is known about colorectal cancer virus communities. We addressed this knowledge gap by identifying differences in colonic virus communities in the stool of colorectal cancer patients and how they compared to bacterial community differences. The results suggested an indirect role for the virome in impacting colorectal cancer by modulating the associated bacterial community. These findings both support the idea of a biological role for viruses in colorectal cancer and provide a new understanding of basic colorectal cancer etiology.

scholarly journals BMI and age associated variations in the gut microbiome: A pan India, cross sectional study

2021 ◽  
Author(s):  
Kumaresan Nallasamy ◽  
Sucheta Gokhale ◽  
Anirban Bhaduri ◽  
Ashok Kumar Dubey
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
Age Groups ◽  
Normal Subjects ◽  
Cross Sectional Study ◽  
Gut Bacteria ◽  
The Other ◽  
Cross Sectional ◽  
Other Hand

Abstract In the current study, we aimed to investigate the association between gut microbiome composition and two physiological factors, BMI and age. We did not observe a significant relationship between occurrence of gut bacteria with BMI or age alone. On the other hand, we observed BMI and age together played an important role in impacting gut microbiota composition. Comparison of the microbiota of normal and obese subjects for the each of 20s and 50s group revealed 13 gut bacteria that show significantly different relative abundance in the two groups. We observed that certain organisms show opposite trends within the two age groups. Haemophilus parainfluenzae relative abundance was found to be increased in obese-20s group while reduced in obese-50s group. Relative abundance of organisms such as Mitsuokella jalaludini and Blautia obeum were reduced in obese-20s group while increased in obese-50s group as compared to the normal subjects of respective age group. On the other hand, a reduction in the average relative abundance of both M. jalaludini and B. obeum for obese group as compared to the normal in pan-India only BMI-based group comparison. While studying obesity-related gut microbiota changes, it is critical to consider multiple factors such as age and geography into the study design.

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