The Gut Microbiome and Colorectal Cancer

2021 ◽  
pp. 63-96
Author(s):  
Amy I. Yu ◽  
Grace Y. Chen
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiome

scholarly journals Postoperative Complications Are Associated with Long-Term Changes in the Gut Microbiota Following Colorectal Cancer Surgery

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 246
Author(s):  
Felix C.F. Schmitt ◽  
Martin Schneider ◽  
William Mathejczyk ◽  
Markus A. Weigand ◽  
Jane C. Figueiredo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Postoperative Complications ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Tumor Resection ◽  
Microbial Composition ◽  
Colorectal Cancer Surgery ◽  
Long Term Changes ◽  
Stool Samples

Changes in the gut microbiome have already been associated with postoperative complications in major abdominal surgery. However, it is still unclear whether these changes are transient or a long-lasting effect. Therefore, the aim of this prospective clinical pilot study was to examine long-term changes in the gut microbiota and to correlate these changes with the clinical course of the patient. Methods: In total, stool samples of 62 newly diagnosed colorectal cancer patients undergoing primary tumor resection were analyzed by 16S-rDNA next-generation sequencing. Stool samples were collected preoperatively in order to determine the gut microbiome at baseline as well as at 6, 12, and 24 months thereafter to observe longitudinal changes. Postoperatively, the study patients were separated into two groups—patients who suffered from postoperative complications (n = 30) and those without complication (n = 32). Patients with postoperative complications showed a significantly stronger reduction in the alpha diversity starting 6 months after operation, which does not resolve, even after 24 months. The structure of the microbiome was also significantly altered from baseline at six-month follow-up in patients with complications (p = 0.006). This was associated with a long-lasting decrease of a large number of species in the gut microbiota indicating an impact in the commensal microbiota and a long-lasting increase of Fusobacterium ulcerans. The microbial composition of the gut microbiome shows significant changes in patients with postoperative complications up to 24 months after surgery.

scholarly journals Bacterial community structure alterations within the colorectal cancer gut microbiome

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mark Loftus ◽  
Sayf Al-Deen Hassouneh ◽  
Shibu Yooseph
Keyword(s):  
Colorectal Cancer ◽  
Community Structure ◽  
Bacterial Community ◽  
Gut Microbiome ◽  
Late Stage ◽  
Bacterial Community Structure ◽  
Whole Genome ◽  
Human Gut ◽  
Fecal Samples ◽  
Human Gut Microbiome

Abstract Background Colorectal cancer is a leading cause of cancer-related deaths worldwide. The human gut microbiome has become an active area of research for understanding the initiation, progression, and treatment of colorectal cancer. Despite multiple studies having found significant alterations in the carriage of specific bacteria within the gut microbiome of colorectal cancer patients, no single bacterium has been unequivocally connected to all cases. Whether alterations in species carriages are the cause or outcome of cancer formation is still unclear, but what is clear is that focus should be placed on understanding changes to the bacterial community structure within the cancer-associated gut microbiome. Results By applying a novel set of analyses on 252 previously published whole-genome shotgun sequenced fecal samples from healthy and late-stage colorectal cancer subjects, we identify taxonomic, functional, and structural changes within the cancer-associated human gut microbiome. Bacterial association networks constructed from these data exhibited widespread differences in the underlying bacterial community structure between healthy and colorectal cancer associated gut microbiomes. Within the cancer-associated ecosystem, bacterial species were found to form associations with other species that are taxonomically and functionally dissimilar to themselves, as well as form modules functionally geared towards potential changes in the tumor-associated ecosystem. Bacterial community profiling of these samples revealed a significant increase in species diversity within the cancer-associated gut microbiome, and an elevated relative abundance of species classified as originating from the oral microbiome including, but not limited to, Fusobacterium nucleatum, Peptostreptococcus stomatis, Gemella morbillorum, and Parvimonas micra. Differential abundance analyses of community functional capabilities revealed an elevation in functions linked to virulence factors and peptide degradation, and a reduction in functions involved in amino-acid biosynthesis within the colorectal cancer gut microbiome. Conclusions We utilize whole-genome shotgun sequenced fecal samples provided from a large cohort of late-stage colorectal cancer and healthy subjects to identify a number of potentially important taxonomic, functional, and structural alterations occurring within the colorectal cancer associated gut microbiome. Our analyses indicate that the cancer-associated ecosystem influences bacterial partner selection in the native microbiota, and we highlight specific oral bacteria and their associations as potentially relevant towards aiding tumor progression.

Alterations in the Oral and Gut Microbiome of Colorectal Cancer Patients and Association with Host Clinical Factors

2021 ◽  
Author(s):  
Yao Wang ◽  
Yao Zhang ◽  
Yun Qian ◽  
Yuan‐Hong Xie ◽  
Shan‐Shan Jiang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Gut Microbiome ◽  
Clinical Factors ◽  
Colorectal Cancer Patients

scholarly journals Stacking and Chaining of Normalisation Methods in Deep Learning-based Classification of Colorectal Cancer using Gut Microbiome Data

IEEE Access ◽  
2021 ◽  
pp. 1-1
Author(s):  
Mwenge Mulenga ◽  
Sameem Abdul Kareem ◽  
Aznul Qalid Md Sabri ◽  
Manjeevan Seera
Keyword(s):  
Colorectal Cancer ◽  
Deep Learning ◽  
Gut Microbiome ◽  
Microbiome Data

scholarly journals A Metabolic Model of Intestinal Secretions: The Link between Human Microbiota and Colorectal Cancer Progression

Metabolites ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 456
Author(s):  
Pejman Salahshouri ◽  
Modjtaba Emadi-Baygi ◽  
Mahdi Jalili ◽  
Faiz M. Khan ◽  
Olaf Wolkenhauer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Gut Microbiome ◽  
Metabolic Model ◽  
System Level ◽  
Mathematical Framework ◽  
Bacterial Populations ◽  
Colorectal Cancer Progression ◽  
Genome Scale ◽  
High Throughput Data Analysis

The human gut microbiota plays a dual key role in maintaining human health or inducing disorders, for example, obesity, type 2 diabetes, and cancers such as colorectal cancer (CRC). High-throughput data analysis, such as metagenomics and metabolomics, have shown the diverse effects of alterations in dynamic bacterial populations on the initiation and progression of colorectal cancer. However, it is well established that microbiome and human cells constantly influence each other, so it is not appropriate to study them independently. Genome-scale metabolic modeling is a well-established mathematical framework that describes the dynamic behavior of these two axes at the system level. In this study, we created community microbiome models of three conditions during colorectal cancer progression, including carcinoma, adenoma and health status, and showed how changes in the microbial population influence intestinal secretions. Conclusively, our findings showed that alterations in the gut microbiome might provoke mutations and transform adenomas into carcinomas. These alterations include the secretion of mutagenic metabolites such as H2S, NO compounds, spermidine and TMA, as well as the reduction of butyrate. Furthermore, we found that the colorectal cancer microbiome can promote inflammation, cancer progression (e.g., angiogenesis) and cancer prevention (e.g., apoptosis) by increasing and decreasing certain metabolites such as histamine, glutamine and pyruvate. Thus, modulating the gut microbiome could be a promising strategy for the prevention and treatment of CRC.

scholarly journals Interaction between Host MicroRNAs and the Gut Microbiota in Colorectal Cancer

mSystems ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Ce Yuan ◽  
Michael B. Burns ◽  
Subbaya Subramanian ◽  
Ran Blekhman
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Mirna Expression ◽  
Gut Microbiome ◽  
Noncoding Rna ◽  
Microbial Community Composition ◽  
Host Cells ◽  
Microbiome Composition ◽  
Small Noncoding Rna

ABSTRACT Although variation in gut microbiome composition has been linked with colorectal cancer (CRC), the factors that mediate the interactions between CRC tumors and the microbiome are poorly understood. MicroRNAs (miRNAs) are known to regulate CRC progression and are associated with patient survival outcomes. In addition, recent studies suggested that host miRNAs can also regulate bacterial growth and influence the composition of the gut microbiome. Here, we investigated the association between miRNA expression and microbiome composition in human CRC tumor and normal tissues. We identified 76 miRNAs as differentially expressed (DE) in tissue from CRC tumors and normal tissue, including the known oncogenic miRNAs miR-182, miR-503, and mir-17~92 cluster. These DE miRNAs were correlated with the relative abundances of several bacterial taxa, including Firmicutes , Bacteroidetes , and Proteobacteria . Bacteria correlated with DE miRNAs were enriched with distinct predicted metabolic categories. Additionally, we found that miRNAs that correlated with CRC-associated bacteria are predicted to regulate targets that are relevant for host-microbiome interactions and highlight a possible role for miRNA-driven glycan production in the recruitment of pathogenic microbial taxa. Our work characterized a global relationship between microbial community composition and miRNA expression in human CRC tissues. IMPORTANCE Recent studies have found an association between colorectal cancer (CRC) and the gut microbiota. One potential mechanism by which the microbiota can influence host physiology is through affecting gene expression in host cells. MicroRNAs (miRNAs) are small noncoding RNA molecules that can regulate gene expression and have important roles in cancer development. Here, we investigated the link between the gut microbiota and the expression of miRNA in CRC. We found that dozens of miRNAs are differentially regulated in CRC tumors and adjacent normal colon and that these miRNAs are correlated with the abundance of microbes in the tumor microenvironment. Moreover, we found that microbes that have been previously associated with CRC are correlated with miRNAs that regulate genes related to interactions with microbes. Notably, these miRNAs likely regulate glycan production, which is important for the recruitment of pathogenic microbial taxa to the tumor. This work provides a first systems-level map of the association between microbes and host miRNAs in the context of CRC and provides targets for further experimental validation and potential interventions.

scholarly journals The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ane Sørlie Kværner ◽  
Einar Birkeland ◽  
Cecilie Bucher-Johannessen ◽  
Elina Vinberg ◽  
Jan Inge Nordby ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Screening ◽  
Gut Microbiome ◽  
Precancerous Lesions ◽  
Colorectal Carcinogenesis ◽  
Screening Tools ◽  
Screening Methods ◽  
Crc Screening ◽  
Link Type ◽  
Incidence And Mortality

Abstract Background Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. Methods The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50–74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. Discussion The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high. Trial registration ClinicalTrials.gov Identifier: NCT01538550.

scholarly journals A theoretical model of temperate phages as mediators of gut microbiome dysbiosis

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 997 ◽  
Author(s):  
Derek M. Lin ◽  
Henry C. Lin
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bacterial Community ◽  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Functional Changes ◽  
Inflammatory Bowel ◽  
Insight Into

Bacteriophages are the most prominent members of the gut microbiome, outnumbering their bacterial hosts by a factor of 10. Phages are bacteria-specific viruses that are gaining attention as highly influential regulators of the gut bacterial community. Dysregulation of the gut bacterial community contributes to dysbiosis, a microbiome disorder characterized by compositional and functional changes that contribute to disease. A role for phages in gut microbiome dysbiosis is emerging with evidence that the gut phage community is altered in dysbiosis-associated disorders such as colorectal cancer and inflammatory bowel disease. Several recent studies have linked successful fecal microbiota transplantation to uptake of the donor’s gut phage community, offering some insight into why some recipients respond to treatment whereas others do not. Here, we review the literature supporting a role for phages in mediating the gut bacterial community, giving special attention to Western diet dysbiosis as a case study to demonstrate a theoretical phage-based mechanism for the establishment and maintenance of dysbiosis.

scholarly journals Altered Fecal Small RNA Profiles in Colorectal Cancer Reflect Gut Microbiome Composition in Stool Samples

mSystems ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Sonia Tarallo ◽  
Giulio Ferrero ◽  
Gaetano Gallo ◽  
Antonio Francavilla ◽  
Giuseppe Clerico ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Small Rna ◽  
Gut Microbiome ◽  
Small Rnas ◽  
Area Under The Curve ◽  
Small Rna Sequencing ◽  
Predictive Tool ◽  
Cross Sectional ◽  
Stool Samples

ABSTRACT Dysbiotic configurations of the human gut microbiota have been linked to colorectal cancer (CRC). Human small noncoding RNAs are also implicated in CRC, and recent findings suggest that their release in the gut lumen contributes to shape the gut microbiota. Bacterial small RNAs (bsRNAs) may also play a role in carcinogenesis, but their role has been less extensively explored. Here, we performed small RNA and shotgun sequencing on 80 stool specimens from patients with CRC or with adenomas and from healthy subjects collected in a cross-sectional study to evaluate their combined use as a predictive tool for disease detection. We observed considerable overlap and a correlation between metagenomic and bsRNA quantitative taxonomic profiles obtained from the two approaches. We identified a combined predictive signature composed of 32 features from human and microbial small RNAs and DNA-based microbiome able to accurately classify CRC samples separately from healthy and adenoma samples (area under the curve [AUC] = 0.87). In the present study, we report evidence that host-microbiome dysbiosis in CRC can also be observed by examination of altered small RNA stool profiles. Integrated analyses of the microbiome and small RNAs in the human stool may provide insights for designing more-accurate tools for diagnostic purposes. IMPORTANCE The characteristics of microbial small RNA transcription are largely unknown, while it is of primary importance for a better identification of molecules with functional activities in the gut niche under both healthy and disease conditions. By performing combined analyses of metagenomic and small RNA sequencing (sRNA-Seq) data, we characterized both the human and microbial small RNA contents of stool samples from healthy individuals and from patients with colorectal carcinoma or adenoma. With the integrative analyses of metagenomic and sRNA-Seq data, we identified a human and microbial small RNA signature which can be used to improve diagnosis of the disease. Our analysis of human and gut microbiome small RNA expression is relevant to generation of the first hypotheses about the potential molecular interactions occurring in the gut of CRC patients, and it can be the basis for further mechanistic studies and clinical tests.

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