Microbiota dysbiosis in select human cancers: Evidence of association and causality

Chen, Jie; Domingue, Jada C.; Sears, Cynthia L.

doi:10.1016/j.smim.2017.08.001

Cited by 144 publications

(126 citation statements)

References 109 publications

(164 reference statements)

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“…These findings are interesting since biofilms have also been associated with periodontal disease and F. nucleatum and Porphyromonas spp. are associated with both oral biofilms and colon cancer (4,11,25,30).…”

Section: Discussionmentioning

confidence: 99%

“…KEYWORDS colorectal cancer, transcriptomics, microRNAs, microbiota, biofilm, germfree N umerous 16S rRNA and shotgun metagenomic studies have demonstrated that colorectal cancer (CRC) patients have an altered intestinal microbiota compared to healthy controls (1,2). Colibactin-producing Escherichia coli, enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum among others, are implicated in CRC pathogenesis due to their abilities to produce genotoxins and adhesins which promote proliferation and modulate immune responses in preclinical models (3,4). How these bacteria interact with the rest of the complex microbiota to influence CRC initiation and/or progression is still unclear.…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…Abnormal variations in the intestinal microbiome is a key factor in the development of many metabolic diseases such as obesity, type-2 diabetes, and atherosclerosis (14). In addition, gut microbes play an important role in constipation, diarrhea, colitis, chronic gastritis, urinary tract infections, skin aging, acne, osteoporosis (15), allergic diseases (16), liver cirrhosis (17), depressive disorder (18), cardiovascular diseases (19), lung diseases (9), autoimmune diseases (20), central nervous system disorders (21), and cancers (22). Therefore, the effect of the intestinal microbiome on the body's immune system is not just limited to the intestinal tract but is spread across the entire body.…”

Section: Human Microbiomementioning

confidence: 99%

Opportunities and Challenges of the Human Microbiome in Ovarian Cancer

et al. 2020

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Ovarian cancer is the most lethal malignancy among gynecological cancers worldwide. Most ovarian cancer patients are diagnosed at an advanced stage because of non-specific clinical symptoms. The human microbiome plays a crucial role in maintaining the normal physiological and pathological state of the body. With the development of technologies such as DNA and 16S rRNA sequencing, an increasing number of findings on the role of microbiome in cancers are being reported. Microbiome abnormalities are increasingly associated with diseases, including cancer development, and response to therapies. Some studies have shown the relationship between microbiome changes and ovarian cancer. However, the mechanisms underlying this relationship are not yet fully understood. Here, we summarize the key findings in this regard by focusing on estrogen metabolism and host recognition receptors in microorganisms and changes in the gut or pelvic microbiome in patients with ovarian cancer. We further discuss the potential of using the microbiome as a novel biomarker for cancers. We also highlight the possibility to use microorganisms as a treatment modality to enhance the immune system, activate anti-tumor response, mediate chemotherapy resistance, and ameliorate the adverse effects of the treatment.

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“…Recently, increased abundance of Fusobacterium nucleatum, Bacteroides fragilis, and Escherichia coli have been associated with human CRC [1][2][3] . These species are hypothesized to promote tumorigenesis and/or progression of CRC through up-regulation of oncogenes, modification of intestinal mucus, or damage to host DNA 2,4,5 . In addition to the mere presence or absence of putative carcinogenic bacteria in the gut, the spatial localization and physical interaction with host epithelial cells may be critically important.…”

Section: Introductionmentioning

confidence: 99%

Clinically adaptable polymer enables simultaneous spatial analysis of colonic tissues and biofilms

Macedonia

Drewes

Markham

et al. 2020

Preprint

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Microbial influences on host cells depend upon the identities of the microbes, their spatial localization, and the responses they invoke on specific host cell populations. Multi-modal analyses of both microbes and host cells in a spatially-resolved fashion would enable studies into these complex interactions in native tissue environments, potentially in clinical specimens. While techniques to preserve each of the microbial and host cell compartments have been used to examine tissues and microbes separately, we endeavored to develop approaches to simultaneously analyze both compartments. Herein, we established an original method for mucus preservation using Poloxamer 407 (also known as Pluronic F-127), a thermoreversible polymer with mucus-adhesive characteristics. We demonstrate that this approach can preserve spatiallydefined compartments of the mucus bi-layer in the colon and the bacterial communities within, compared with their marked absence when tissues were processed with traditional formalin-fixed paraffin-embedded (FFPE) pipelines. Additionally, antigens for antibody staining of host cells were preserved and signal intensity for 16S rRNA fluorescence in situ hybridization (FISH) was enhanced in Poloxamer-fixed samples. This in turn enabled us to integrate multi-modal analysis using a modified multiplex immunofluorescence (MxIF) protocol. Importantly, we have formulated Poloxamer 407 to polymerize and crosslink at room temperature for use in clinical workflows. These results suggest that the fixative formulation of Poloxamer 407 can be integrated into biospecimen collection pipelines for simultaneous analysis of microbes and host cells.3 Introduction:

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Microbiota dysbiosis in select human cancers: Evidence of association and causality

Cited by 144 publications

References 109 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

Opportunities and Challenges of the Human Microbiome in Ovarian Cancer

Clinically adaptable polymer enables simultaneous spatial analysis of colonic tissues and biofilms

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