scholarly journals A comprehensive analysis of the microbiota composition and gene expression in colorectal cancer

2019 ◽  
Author(s):  
Qian Zhang ◽  
Huan Zhao ◽  
Dedong Wu ◽  
Dayong Cao ◽  
Wang Ma
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Bile Secretion ◽  
Colorectal Carcinogenesis ◽  
The Cancer Genome Atlas ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Sequencing Data ◽  
Keywords Colorectal Cancer

Abstract Subject: The dysbiosis of gut microbiota is pivotal in colorectal carcinogenesis. However, the synergy between an altered gut microbiota composition and differential gene expression of specific genes in colorectal cancer (CRC) remains elusive. Method: The gut microbiota dataset with number SRP158779, which contained 19 CRC samples and 19 normal samples, was downloaded from the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) database. The 16S rRNA gene sequences from this dataset were clustered into operational taxonomic units (OTUs); thereafter, the OTUs that were differentially enriched in CRC were identified and classified, followed by prediction of their functions. Additionally, RNA sequencing data from CRC samples was obtained from The Cancer Genome Atlas project (TCGA), and the differentially expressed genes (DEGs) and enriched pathways were identified. Finally, similar pathways that were significantly enriched in both differential OTUs and DEGs were screened. Key genes related to these pathways were executed the prognosis analysis. Results: The presence of Proteobacteria and Fusobacteria increased considerably in CRC samples; conversely, the abundance of Firmicute and Spirochaetes decreased markedly. In particular, the genera Fusobacterium , Catenibacterium , and Shewanella were detectable in tumor samples. Moreover, 246 DEGs were identified between tumor and normal tissues. Both DEGs and microbiota were involved in bile secretion and steroid hormone biosynthesis pathways. Finally, CYP3A4 and ABCG2 expression in CRC was related to the prognostic outcomes of CRC patients. Conclusion: Identifying the complicated interplay between gut microbiota and the DEGs could help in further understanding the pathogenesis of CRC, and these findings would enable better diagnosis and treatment of CRC patients. Keywords: colorectal cancer, gut microflora, gene expression, pathways enrichment, survival analysis

scholarly journals A comprehensive analysis of the microbiota composition and gene expression in colorectal cancer

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Qian Zhang ◽  
Huan Zhao ◽  
Dedong Wu ◽  
Dayong Cao ◽  
Wang Ma
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Bile Secretion ◽  
Colorectal Carcinogenesis ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Rna Sequences ◽  
Normal Tissues ◽  
Hormone Biosynthesis ◽  
Cytochrome P450 Family

Abstract Background The dysregulation of gut microbiota is pivotal in colorectal carcinogenesis. Meanwhile, altered gut microbiome may affect the development of intestinal diseases through interaction with the host genes. However, the synergy between the altered gut microbiota composition and differential expression of specific genes in colorectal cancer (CRC) remains elusive. Thus, we integrated the data from 16S rRNA gene sequences and RNA sequences to investigate the potential relationship between genes and gut microbes in patients with CRC. Results Compared with normal samples, the presence of Proteobacteria and Fusobacteria increased considerably in CRC samples; conversely, the abundance of Firmicutes and Spirochaetes decreased markedly. In particular, the genera Fusobacterium, Catenibacterium, and Shewanella were only detected in tumor samples. Meanwhile, a closely interaction between Butyricimonas and Clostridium was observed in the microbiome network. Furthermore, a total of 246 (differentially expressed genes) DEGs were identified between tumor and normal tissues. Both DEGs and microbiota were involved in bile secretion and steroid hormone biosynthesis pathways. Finally, genes like cytochrome P450 family 3 subfamily A member 4 (CYP3A4) and ATP binding cassette subfamily G member 2 (ABCG2) enriched in these two pathways were connected with the prognosis of CRC, and CRC patients with low expression level of CYP3A4 and ABCG2 had longer survival time. Conclusion Identifying the complicated interaction between gut microbiota and the DEGs contributed to further understand the pathogenesis of CRC, and these findings might enable better diagnosis and treatment of CRC patients.

scholarly journals Gut Microbiota Composition across Normal Range Prostate-Specific Antigen Levels

2021 ◽  
Vol 11 (12) ◽  
pp. 1381
Author(s):  
Han-Na Kim ◽  
Jae-Heon Kim ◽  
Yoosoo Chang ◽  
Dongmin Yang ◽  
Hyung-Lae Kim ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Sequencing Data ◽  
Normal Range ◽  
Cross Sectional ◽  
Gut Microbiota Composition

Animal studies have shown the interaction between androgens and the gut microbiome directly and indirectly; however, limited evidence from human studies is available. To evaluate the association between prostate-specific antigen (PSA) levels within the normal range, reflective of androgen receptor activity, and the gut microbiota composition, a cross-sectional analysis was performed in 759 Korean men aged between 25 and 78 years with normal PSA levels of ≤4.0 ng/mL. We evaluated the biodiversity of gut microbiota as well as the taxonomic and functional signatures associated with PSA levels using 16S rRNA gene sequencing data. PSA levels within the normal range were categorized into three groups: lowest quartile (G1), interquartile range (G2, reference), and highest quartile (G3). The G3 group had higher microbial richness than the G2 group, although it was dominated by a few bacteria. An increase in Escherichia/Shigella abundance and a reduction in Megamonas abundance in the G3 group were also detected. A U-shaped relationship was observed between the three groups across most analyses, including biodiversity, taxonomic composition, and inferred pathways in the gut microbiota. This study showed different microbiota patterns across PSA levels within the normal range. Further studies are required to elucidate the role of microbiota in regulating PSA levels.

scholarly journals Role of intestinal microbiota in colorectal carcinogenesis (review)

2021 ◽  
Vol 20 (1) ◽  
pp. 68-76
Author(s):  
M. A. Sukhina ◽  
I. A. Lyagina ◽  
A. L. Safin ◽  
S. A. Frolov ◽  
V. N. Kashnikov
Keyword(s):  
Colorectal Cancer ◽  
Cancer Screening ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Colorectal Carcinogenesis ◽  
Pathogenic Microorganisms ◽  
Microbiota Composition ◽  
Qualitative And Quantitative ◽  
Leading Role

The aim of the review is to show possible links between intestinal microbiota and colorectal carcinogenesis, to describe the procarcinogenic properties of microorganisms associated with the development or proliferation of colorectal cancer. The gut microbiota plays a leading role in metabolism, providing important metabolites to the macroorganism. In humans, there is a spatial variability in the qualitative and quantitative microbiota composition. The intestinal microbiota provides the colony resistance, protecting it from colonization by opportunistic and pathogenic microorganisms. There is more and more data on the role of the gut microbiota in the development of colorectal cancer. The profound study of the gut microbiome in various populations is required, which will allow to identify other microorganisms associated with the development or proliferation of colorectal cancer. It can be used as biomarkers for colorectal cancer screening and predicting the response to immunotherapy.

scholarly journals Circulating let-7e-5p, miR-106a-5p, miR-28-3p, and miR-542-5p as a Promising microRNA Signature for the Detection of Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1493
Author(s):  
Camila Meirelles S. Silva ◽  
Mateus C. Barros-Filho ◽  
Deysi Viviana T. Wong ◽  
Julia Bette H. Mello ◽  
Livia Maria S. Nobre ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Unmet Need ◽  
Area Under The Curve ◽  
Discrimination Performance ◽  
Colorectal Carcinogenesis ◽  
The Cancer Genome Atlas ◽  
Colon Perforation ◽  
Data Series ◽  
Predictive Tool ◽  
Incidence And Mortality

Colorectal cancer (CRC) is a disease with high incidence and mortality. Colonoscopy is a gold standard among tests used for CRC traceability. However, serious complications, such as colon perforation, may occur. Non-invasive diagnostic procedures are an unmet need. We aimed to identify a plasma microRNA (miRNA) signature for CRC detection. Plasma samples were obtained from subjects (n = 109) at different stages of colorectal carcinogenesis. The patients were stratified into a non-cancer (27 healthy volunteers, 17 patients with hyperplastic polyps, 24 with adenomas), and a cancer group (20 CRC and 21 metastatic CRC). miRNAs (381) were screened by TaqMan Low-Density Array. A classifier based on four differentially expressed miRNAs (miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p) was able to discriminate cancer versus non-cancer cases. The overexpression of these miRNAs was confirmed by RT-qPCR, and a cross-study validation step was implemented using eight data series retrieved from Gene Expression Omnibus (GEO). In addition, another external data validation using CRC surgical specimens from The Cancer Genome Atlas (TCGA) was carried out. The predictive model’s performance in the validation set was 76.5% accuracy, 59.4% sensitivity, and 86.8% specificity (area under the curve, AUC = 0.716). The employment of our model in the independent publicly available datasets confirmed a good discrimination performance in five of eight datasets (median AUC = 0.823). Applying this algorithm to the TCGA cohort, we found 99.5% accuracy, 99.7% sensitivity, and 90.9% specificity (AUC = 0.998) when the model was applied to solid colorectal tissues. Overall, we suggest a novel signature of four circulating miRNAs, i.e., miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p, as a predictive tool for the detection 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 Integrative analysis of gut microbiota composition, host colonic gene expression and intraluminal metabolites in aging C57BL/6J mice

Aging ◽  
2018 ◽  
Vol 10 (5) ◽  
pp. 930-950 ◽  
Author(s):  
Benthe van der Lugt ◽  
Fenni Rusli ◽  
Carolien Lute ◽  
Andreas Lamprakis ◽  
Ethel Salazar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gut Microbiota ◽  
Integrative Analysis ◽  
Microbiota Composition ◽  
Gut Microbiota Composition

scholarly journals Encapsulated cyclosporine does not change the composition of the human microbiota when assessed ex vivo and in vivo

2020 ◽  
Vol 69 (6) ◽  
pp. 854-863
Author(s):  
Catherine O'Reilly ◽  
Órla O’Sullivan ◽  
Paul D. Cotter ◽  
Paula M. O’Connor ◽  
Fergus Shanahan ◽  
...  
Keyword(s):  
Pilot Study ◽  
Gut Microbiota ◽  
Targeted Delivery ◽  
Healthy Subjects ◽  
Ex Vivo ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Faecal Samples

Introduction. Management of steroid-refractory ulcerative colitis has predominantly involved treatment with systemic cyclosporine A (CyA) and infliximab. Aim. The purpose of this study was to assess the effect of using a colon-targeted delivery system CyA formulation on the composition and functionality of the gut microbiota. Methodology. Ex vivo faecal fermentations from six healthy control subjects were treated with coated minispheres (SmPill) with (+) or without (−) CyA and compared with a non-treated control in a model colon system. In addition, the in vivo effect of the SmPill+CyA formulation was investigated by analysing the gut microbiota in faecal samples collected before the administration of SmPill+CyA and after 7 consecutive days of administration from eight healthy subjects who participated in a pilot study. Results. Analysis of faecal samples by 16S rRNA gene sequencing indicated little variation in the diversity or relative abundance of the microbiota composition before or after treatment with SmPill minispheres with or without CyA ex vivo or with CyA in vivo. Short-chain fatty acid profiles were evaluated using gas chromatography, showing an increase in the concentration of n-butyrate (P=0.02) and acetate (P=0.32) in the faecal fermented samples incubated in the presence of SmPill minispheres with or without CyA. This indicated that increased acetate and butyrate production was attributed to a component of the coated minispheres rather than an effect of CyA on the microbiota. Butyrate and acetate levels also increased significantly (P=0.05 for both) in the faecal samples of healthy individuals following 7 days’ treatment with SmPill+CyA in the pilot study. Conclusion. SmPill minispheres with or without CyA at the clinically relevant doses tested here have negligible direct effects on the gut microbiota composition. Butyrate and acetate production increased, however, in the presence of the beads in an ex vivo model system as well as in vivo in healthy subjects. Importantly, this study also demonstrates the relevance and value of using ex vivo colon models to predict the in vivo impact of colon-targeted drugs directly on the gut microbiota.

scholarly journals Identification of an extracellular vesicle-related gene signature in the prediction of pancreatic cancer clinical prognosis

2020 ◽  
Vol 40 (12) ◽  
Author(s):  
Dafeng Xu ◽  
Yu Wang ◽  
Kailun Zhou ◽  
Jincai Wu ◽  
Zhensheng Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Immune Cells ◽  
Prognostic Value ◽  
Tumor Tissue ◽  
Clinical Stage ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
Clinical Prognosis

Abstract Although extracellular vesicles (EVs) in body fluid have been considered to be ideal biomarkers for cancer diagnosis and prognosis, it is still difficult to distinguish EVs derived from tumor tissue and normal tissue. Therefore, the prognostic value of tumor-specific EVs was evaluated through related molecules in pancreatic tumor tissue. NA sequencing data of pancreatic adenocarcinoma (PAAD) were acquired from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC). EV-related genes in pancreatic cancer were obtained from exoRBase. Protein–protein interaction (PPI) network analysis was used to identify modules related to clinical stage. CIBERSORT was used to assess the abundance of immune and non-immune cells in the tumor microenvironment. A total of 12 PPI modules were identified, and the 3-PPI-MOD was identified based on the randomForest package. The genes of this model are involved in DNA damage and repair and cell membrane-related pathways. The independent external verification cohorts showed that the 3-PPI-MOD can significantly classify patient prognosis. Moreover, compared with the model constructed by pure gene expression, the 3-PPI-MOD showed better prognostic value. The expression of genes in the 3-PPI-MOD had a significant positive correlation with immune cells. Genes related to the hypoxia pathway were significantly enriched in the high-risk tumors predicted by the 3-PPI-MOD. External databases were used to verify the gene expression in the 3-PPI-MOD. The 3-PPI-MOD had satisfactory predictive performance and could be used as a prognostic predictive biomarker for pancreatic cancer.

scholarly journals Colonisation potential of plantaricin-producing Lactobacillus plantarum SF9C andS-layer-carrying Lactobacillus brevis SF9B among gut microbiota

2020 ◽  
Author(s):  
Katarina Butorac ◽  
Martina Banic ◽  
Jasna Novak ◽  
Andreja Leboš Pavunc ◽  
Ksenija Uroic ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Lactobacillus Plantarum ◽  
Lactobacillus Brevis ◽  
Illumina Miseq ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Combined Application ◽  
Probiotic Potential ◽  
Gut Microbiota Composition

Abstract Background: The influence of an S-layer-carrying strain Lactobacillus brevis SF9B and a plantaricin-producing strain Lactobacillus plantarum SF9C on the gut microbiota composition was evaluated in the rats. Considering the probiotic potential of Lb. brevis SF9B, this study aimed to examine the antibacterial activity of Lb. plantarum SF9C and potential for their in vivo colonisation, which could be the basis for the investigation of their synergistic functionality. Results: A plantaricin-encoding cluster was identified in Lb. plantarum SF9C, a strain which efficiently inhibited the growth of Listeria monocytogenes ATCC®19111™ and Staphylococcus aureus 3048. Contrary to the plantaricin-producing SF9C strain, the S-layer-carrying SF9B strain excluded Escherichia coli 3014 and Salmonella enterica serovar Typhimurium FP1 from adhesion to Caco-2 cells. Finally, DGGE analysis of the V2-V3 region of the 16S rRNA gene confirmed the transit of two selected lactobacilli through the gastrointestinal tract (GIT). Microbiome profiling via the Illumina MiSeq platform revealed the prevalence of Lactobacillus spp. in the gut microbiota of rats suggesting their colonisation potential in GIT.Conclusion: The combined application of Lb. plantarum SF9C and Lb. brevis SF9B could influence the intestinal microbiota composition, which is reflected through the increased abundance of Lactobacillus genus, but also through altered abundances of other bacterial genera, either in the model of healthy or aberrant microbiota of rats. The obtained results contributed to the functional aspects of SF9C and SF9B strains which could be incorporated in the probiotic-containing functional foods and therefore have a beneficial influence on the gut microbiota composition.

scholarly journals Yoghurt Consumption is Associated With Transient Changes in the Composition of the Human Gut Microbiome

2020 ◽  
Author(s):  
Caroline Ivanne Le Roy ◽  
Alexander Kurilshikov ◽  
Emily Leeming ◽  
Alessia Visconti ◽  
Ruth Bowyer ◽  
...  
Keyword(s):  
16S Rrna ◽  
Gut Microbiota ◽  
Visceral Fat ◽  
Gut Microbiome ◽  
Body Weight Gain ◽  
Healthy Eating Index ◽  
Rrna Gene ◽  
Metagenomic Sequencing ◽  
Sequencing Data ◽  
Shotgun Metagenomic Sequencing

Abstract Background: Yoghurt contains live bacteria that could contribute via modulation of the gut microbiota to its reported beneficial effects such as reduced body weight gain and lower incidence of type 2 diabetes. To date, the association between yoghurt consumption and the composition of the gut microbiota is underexplored. Here we used clinical variables, metabolomics, 16S rRNA and shotgun metagenomic sequencing data collected on over 1000 predominantly female UK twins to define the link between the gut microbiota and yoghurt-associated health benefits. Results: According to food frequency questionnaires (FFQ), 73% of subjects consumed yoghurt. Consumers presented a healthier diet pattern (healthy eating index: beta = 2.17±0.34; P = 2.72x10-10) and improved metabolic health characterised by reduced visceral fat (beta = -28.18±11.71 g; P = 0.01). According to 16S rRNA gene analyses and whole shotgun metagenomic sequencing approach consistent taxonomic variations were observed with yoghurt consumption. More specifically, we identified higher abundance of species used as yoghurt starters Streptococcus thermophilus (beta = 0.41±0.051; P = 6.14x10-12) and sometimes added Bifidobacterium animalis subsp. lactis (beta = 0.30±0.052; P = 1.49x10-8) in the gut of yoghurt consumers. Replication in 1103 volunteers from the LifeLines-DEEP cohort confirmed the increase of S. thermophilus among yoghurt consumers. Using food records collected the day prior to faecal sampling we showed that increase in these two yoghurt bacteria could be transient. Metabolomics analysis revealed that B. animalis subsp. lactis was associated with 13 faecal metabolites including a 3-hydroxyoctanoic acid, known to be involved in the regulation of gut inflammation.Conclusions: Yoghurt consumption is associated with reduced visceral fat mass and changes in gut microbiome including transient increase of yoghurt-contained species (i.e. S. thermophilus and B. lactis).

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