Interaction between Host MicroRNAs and the Gut Microbiota in Colorectal Cancer

Yuan, Ce; Burns, Michael B.; Subramanian, Subbaya; Blekhman, Ran

doi:10.1128/msystems.00205-17

Cited by 99 publications

(102 citation statements)

References 88 publications

(110 reference statements)

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“…CRC is an evolving disease, characterized by a series of molecular and microbial changes (14)(15)(16), suggesting a dynamic interplay between the host and intestinal microbiota as the disease progresses. MicroRNAs (miRNAs) have emerged as potential mediators of these host-microbe interactions with their ability to modulate both host (17) and bacterial genes, which can result in shifts in microbiota composition (18,19). In turn, the microbiota is able to modulate host miRNA expression (18,20,21), with F. nucleatum targeting several miRNAs related to CRC pathogenesis (5,22).…”

mentioning

confidence: 99%

Human Colon Mucosal Biofilms and Murine Host Communicate via Altered mRNA and microRNA Expression during Cancer

et al. 2020

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Disrupted interactions between host and intestinal bacteria are implicated in colorectal cancer (CRC) development. However, activities derived from these bacteria and their interplay with the host are unclear. Here, we examine this interplay by performing mouse and microbiota RNA sequencing on colon tissues and 16S and small RNA sequencing on stools from germfree (GF) and gnotobiotic ApcMinΔ850/+;Il10−/− mice associated with microbes from biofilm-positive human CRC tumor (BF+T) and biofilm-negative healthy (BF-bx) tissues. The bacteria in BF+T mice differentially expressed (DE) >2,900 genes, including genes related to bacterial secretion, virulence, and biofilms but affected only 62 host genes. Small RNA sequencing of stools from these cohorts revealed eight significant DE host microRNAs (miRNAs) based on biofilm status and several miRNAs that correlated with bacterial taxon abundances. Additionally, computational predictions suggest that some miRNAs preferentially target bacterial genes while others primarily target mouse genes. 16S rRNA sequencing of mice that were reassociated with mucosa-associated communities from the initial association revealed a set of 13 bacterial genera associated with cancer that were maintained regardless of whether the reassociation inoculums were initially obtained from murine proximal or distal colon tissues. Our findings suggest that complex interactions within bacterial communities affect host-derived miRNA, bacterial composition, and CRC development. IMPORTANCE Bacteria and bacterial biofilms have been implicated in colorectal cancer (CRC), but it is still unclear what genes these microbial communities express and how they influence the host. MicroRNAs regulate host gene expression and have been explored as potential biomarkers for CRC. An emerging area of research is the ability of microRNAs to impact growth and gene expression of members of the intestinal microbiota. This study examined the bacteria and bacterial transcriptome associated with microbes derived from biofilm-positive human cancers that promoted tumorigenesis in a murine model of CRC. The murine response to different microbial communities (derived from CRC patients or healthy people) was evaluated through RNA and microRNA sequencing. We identified a complex interplay between biofilm-associated bacteria and the host during CRC in mice. These findings may lead to the development of new biomarkers and therapeutics for identifying and treating biofilm-associated CRCs.

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confidence: 99%

Human Colon Mucosal Biofilms and Murine Host Communicate via Altered mRNA and microRNA Expression during Cancer

et al. 2020

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“…Similar to previous reports in humans, we found variations to the microbiota composition between different NHP subjects. Previous studies suggest that this variation between individuals can be attributed to factors such as genetics, dietary preferences and other factors [1,32,33]. We found that both small and large intestinal tissues have significant interindividual variations, although the statistical significance in the small intestinal tissues is more pronounced compared to the large intestines (PERMANOVA, P < 9.999e-05 vs. P < 0.05).…”

Section: Discussionmentioning

confidence: 40%

“…The human gastrointestinal (GI) tract harbors trillions of microorganisms, including thousands of bacterial species, termed the microbiota [1]. It has become evident that the gut microbiota is important in regulating and maintaining the health of the host and is implicated in many diseases, such as cancers [1][2][3][4][5]. Despite numerous studies indicating important roles of microbiota in diseases, many of these studies have largely focused on the taxonomic composition of the microbiota [6].…”

Section: Introductionmentioning

confidence: 99%

“…Without a functional microbiota, the colon epithelia undergo autophagy and fail to maintain normal structure and function [14]. More importantly, these metabolic interactions have important implications in colorectal cancer, the second most deadly cancer in the United States [1,5,7,8,[15][16][17][18]. Furthermore, bile acids, produced by the liver and modified by the intestinal bacteria, have been shown play signaling roles that impact the progression of obesity and the metabolic syndrome [19].…”

Section: Introductionmentioning

confidence: 99%

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Mucosal microbiota and metabolome along the intestinal tracts reveals location specific relationship

Yuan

Graham

Staley

et al. 2018

Preprint

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BackgroundThe intestinal microbiota has been recognized as an important component for maintaining human health. The perturbation to its structure has been implicated in many diseases, such as obesity and cancers. The microbiota is highly metabolically active and plays a role in many metabolic pathways absent from the human host. Altered microbiota metabolism has also been linked to obesity, cardiovascular disease, and colorectal cancer. However, there is a gap in the current knowledge of how the microbiota interacts with its host. Here we performed an integrated analysis between the mucosal-associated microbiota and the mucosal tissue metabolomics in healthy non-human primates (NHPs) to investigate these relationships. ResultsWe found that the overall microbiota composition is influenced by both the tissue location as well as the host individual. The NHPs intestinal microbiota predominantly comprised of members of the phyla Firmicutes, Bacteroidetes, and Proteobacteria. The large intestines contain more Spirochaetes, Tenericutes, and Lentisphaera phyla members. The small intestinal tissues have no significantly different microbiota compositions, while the cecum and distal colon differ greatly in the microbiota compositions. The metabolomics profile reveals a total of 140 metabolites with different concentration between the small and large intestines. The correlations between microbiota and tissue metabolites showed a dense and interconnected network in the small intestines while a sparse network in the large intestines. ConclusionsOur analysis revealed an intricate global relationship between the microbiota and the host tissue metabolome that is mainly driven by the distal colon. Most importantly, we found location specific microbiota-metabolite correlations that have potential implications for studying host-microbiota metabolic interactions.

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“…Several recent studies have shown that the microbiome can affect gene regulation in interacting host cells, [43][44][45] and in particular in colonic tumors. 46 In addition, the effects of immune elements, tumor heterogeneity, epigenetic factors, and the developmental history of the tissue may also be important for interaction with the microbiome. 47 It is also likely that the viral community present in the gut plays an important role, interacting with both host and microbial cells.…”

Section: Next Steps and Open Questionsmentioning

confidence: 99%

Integrating tumor genomics into studies of the microbiome in colorectal cancer

Burns

Blekhman

2018

Gut Microbes

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Although the gut microbiome has been linked to colorectal cancer (CRC) development, associations of microbial taxa with CRC status are often inconsistent across studies. We have recently shown that tumor genomics, a factor that is rarely incorporated in analyses of the CRC microbiome, has a strong effect on the composition of the microbiota. Here, we discuss these results in the wider context of studies characterizing interaction between host genetics and the microbiome, and describe the implications of our findings for understanding the role of the microbiome in CRC.

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Interaction between Host MicroRNAs and the Gut Microbiota in Colorectal Cancer

Cited by 99 publications

References 88 publications

Human Colon Mucosal Biofilms and Murine Host Communicate via Altered mRNA and microRNA Expression during Cancer

Human Colon Mucosal Biofilms and Murine Host Communicate via Altered mRNA and microRNA Expression during Cancer

Mucosal microbiota and metabolome along the intestinal tracts reveals location specific relationship

Integrating tumor genomics into studies of the microbiome in colorectal cancer

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