CRC-associated microbiota
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ABSTRACT:
PROVIDER: PRJEB56178 | ENA |
REPOSITORIES: ENA
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Project description:Background: In vitro models are an essential tool towards understanding the molecular characteristics of colorectal cancer (CRC) and the testing of therapies for CRC. To this end we established 21 novel CRC cell lines of which six were derived from liver metastases. Extensive genetic, genomic, transcriptomic and methylomic profiling was performed in order to characterize these new cell lines and all data is made publically available. Additionally, sensitivity of oxaliplatin was tested as a measure for chemotherapy resistance. Results: DNA copy-number alterations (CNA) were compared between primary and metastasis derived cell lines. In concordance with previous studies copy-number gain of chr20, and loss of chr8p were found highly specific for liver metastases. Previously reported BRAF-mutation associated DNA methylation profiles could be validated on the genome-wide DNA methylation profiles of these cell lines. 47.6% of the loci previously reported to associate with BRAF mutation status were reproduced in this dataset. When examining the gene expression profiles in conjunction with these DNA methylation results, we identified 20 genes of which the gene expression correlated with the DNA methylation status, including MEIS1, LRAT and STC2. These genes have previously been reported to be subject to transcriptional regulation through DNA hypermethylation, validating our approach. Conclusions: By combining mutation profiles with CNA and gene expression profiles we constructed an overview of the alterations in the major CRC-related signalling pathways. The mutation profiles, along with the genome, transcriptome and methylome data of these cell lines will be made publically available . This combined dataset puts these cell lines among the best characterized CRC cell lines, allowing researchers to select appropriate cell line models for their particular experiment, making optimal use of these novel cell lines as in vitro model for CRC. 21 CRC cell lines were analyzed
2016-02-29 | E-GEOD-67772 | biostudies-arrayexpress
Project description:Swim bladder nematode-associated microbiota
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Project description:Increasing importance in the onset and progression from colonic adenomatous polyps (AP) to colorectal cancer (CRC) has been attributed to the gut microbiota and the oncometabolites they may produce. To comprehensively study the microbial spatial variations and role of microbiota in CRC progression, multiple niches from the gastrointestinal system have to be investigated. We collected saliva, tissue and stool samples from 61 patients, including 46 CRC patients and 15 AP patients, well matched in age and sex, who were undergoing surgery in 2018 at the Careggi University Hospital (Florence, Italy). For all samples and locations we surveyed microbial composition through 16S ribosomal RNA and metabolites using NMR, and compared them across tissues and disease state, also considering CRC TNM staging. Our result suggest the importance of microbiota communities and derived oncometabolites in CRC development. Such association can be a forerunner for future studies on CRC/AP management.
2023-05-03 | GSE217490 | GEO
Project description:Several lines of evidence suggest that inflammation plays a pivotal role in the development and progression of CRC and can be unleashed by the loss of innate immunosurveillance. The complement system is a well characterized first line of defense against pathogens and a central component of the immune responses. As such, the complement system is an important determinant in the maintenance of intestinal homeostasis and emerging evidences suggest that complement dysregulation is involved in the development and progression of CRC. Here we show that in CRC patients CpG island methylation occurs in the gene encoding for the complement anaphylatoxin C3a receptor (c3aR) and strong C3aR down-regulation resulted in decreased overall survival and events-free survival in CRC patients. Ablation of c3ar in mouse models of CRC resulted in the establishment of a pro-inflammatory microbial flora, which fostered strong Th1/Th17 immune responses and a striking increase in tumor incidence and growth that were both dependent on the microbiota. Our findings highlight a previously unrecognized tumor oncosuppressive role for C3aR in CRC that could be exploited as a biomarker for more effective therapeutic intervention.
2020-02-01 | E-MTAB-8500 | biostudies-arrayexpress
Project description:The human intestinal microbiota associated with rats produces in vivo a soluble(s) factor(s) that down-regulates the expression of genes encoding for the Shiga toxin II in E. coli O157:H7. The Shiga toxin II is one of the major virulence factors of E. coli enterohemorragic leading to the deadly hemolitic and uremic syndrome. Investigation of the effect of the human intestinal microbiota on the whole transcriptome of EHEC O157:H7 is of major importance to increase our understanding of the pathogen transcriptomic adaptation in response to the human microbiota. We analysed by microarray hybridization the gene expression pattern of EHEC O157:H7 grown in the caecal content of germ-free rats or rats associated with the human microbiota of a healthy human subject. By doing so, we increased our understanding of the regulatory activities of the human gut microbiota on E. coli O157:H7 A first group of twelve weeks old, male, germfree rats was colonized with the human fecal microbiota and a second group was kept germfree and condidered as a controle group. Rats were fed for two weeks with a sterile human type diet, and were sacrificed. E. coli O157:H7 was cultivated for 6 hours in the caecal content of germfree rats and rats associated with the human intestinal microbiota. RNAs were extracted and cDNAs were synthesized, fragmented and biotinylated before being hybridized on Affymetrix E. coli genome 2.0 arrays. The effect of the human intestinal microbiota was investigated by comparing the gene expression level in the caecal content of rats associated with the human microbiota with their expression level in the caecal content of the germfree rats.
2013-09-10 | E-GEOD-37095 | biostudies-arrayexpress
Project description:Human saliva microbiota is phylogenetically divergent among host individuals yet their roles in health and disease are poorly appreciated. We employed a microbial functional gene microarray, HuMiChip 1.0, to reconstruct the global functional profiles of human saliva microbiota from ten healthy and ten caries-active adults. Saliva microbiota in the pilot population featured a vast diversity of functional genes. No significant distinction in gene number or diversity indices was observed between healthy and caries-active microbiota. However, co-presence network analysis of functional genes revealed that caries-active microbiota was more divergent in non-core genes than healthy microbiota, despite both groups exhibited a similar degree of conservation at their respective core genes. Furthermore, functional gene structure of saliva microbiota could potentially distinguish caries-active patients from healthy hosts. Microbial functions such as Diaminopimelate epimerase, Prephenate dehydrogenase, Pyruvate-formate lyase and N-acetylmuramoyl-L-alanine amidase were significantly linked to caries. Therefore, saliva microbiota carried disease-associated functional signatures, which could be potentially exploited for caries diagnosis. The DMFT INDEX (Decayed, Missing, Filled [DMF] teeth index used in dental epidemiology) values are provided for each sample We employed a microbial functional gene microarray, HuMiChip 1.0, to reconstruct the global functional profiles of human saliva microbiota from ten healthy and ten caries-active adults.
2013-08-15 | E-GEOD-49875 | biostudies-arrayexpress
Project description:The effect of oral microbiota on the intestinal microbiota has garnered growing attention as a mechanism linking periodontal diseases to systemic diseases. However, the salivary microbiota is diverse and comprises numerous bacteria with a largely similar composition in healthy individuals and periodontitis patients. Thus, the systemic effects of small differences in the oral microbiota are unclear. In this study, we explored how health-associated and periodontitis-associated salivary microbiota differently colonized the intestine and their subsequent systemic effects by analyzing the hepatic gene expression and serum metabolomic profiles. The salivary microbiota was collected from a healthy individual and a periodontitis patient and gavaged into C57BL/6NJcl[GF] mice. Samples were collected five weeks after administration. Gut microbial communities were analyzed by 16S ribosomal RNA gene sequencing. Hepatic gene expression profiles were analyzed using a DNA microarray and quantitative polymerase chain reaction. Serum metabolites were analyzed by capillary electrophoresis time-of-flight mass spectrometry. The gut microbial composition at the genus level was significantly different between periodontitis-associated microbiota-administered (PAO) and health-associated oral microbiota-administered (HAO) mice. The hepatic gene expression profile demonstrated a distinct pattern between the two groups, with higher expression of Neat1, Mt1, Mt2, and Spindlin1, which are involved in lipid and glucose metabolism. Disease-associated metabolites such as 2-hydroxyisobutyric acid and hydroxybenzoic acid were elevated in PAO mice. These metabolites were significantly correlated with Bifidobacterium, Atomobium, Campylobacter, and Haemophilus, which are characteristic taxa in PAO mice. Conversely, health-associated oral microbiota were associated with higher levels of beneficial serum metabolites in HAO mice. The multi-omics approach used in this study revealed that periodontitis-associated oral microbiota is associated with the induction of disease phenotype when they colonized the gut of germ-free mice.
2022-08-17 | GSE198570 | GEO