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 Distinct Colon Mucosa Microbiomes associated with Tubular Adenomas and Serrated Polyps

2021 ◽  
Author(s):  
Julio Avelar-Barragan ◽  
Lauren DeDecker ◽  
Zachary Lu ◽  
Bretton Coppedge ◽  
William Karnes ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiome ◽  
Microbial Community Composition ◽  
Tubular Adenoma ◽  
Colon Mucosa ◽  
Fecal Samples ◽  
Serrated Polyps ◽  
Microbiome Composition ◽  
Serrated Polyp ◽  
Mechanisms Of Carcinogenesis

Background: Colorectal cancer is the second most deadly and third most common cancer in the world. Its development is heterogenous, with multiple mechanisms of carcinogenesis. Two distinct mechanisms include the adenoma-carcinoma sequence and the serrated pathway. The gut microbiome has been identified as a key player in the adenoma-carcinoma sequence, but its role in serrated carcinogenesis is unclear. In this study, we characterized the gut microbiome of 140 polyp-free and polyp-bearing individuals using colon mucosa and fecal samples to determine if microbiome composition was associated with each of the two key pathways. Results: We discovered significant differences between colon mucosa and fecal samples, explaining 14% of the variation observed in the microbiome. Multiple mucosal samples were collected from each individual to investigate the gut microbiome for differences between polyp and healthy intestinal tissue, but no such differences were found. Colon mucosa sampling revealed that the microbiomes of individuals with tubular adenomas and serrated polyps were significantly different from each other and polyp-free individuals, explaining 2-10% of the variance in the microbiome. Further analysis revealed differential abundances of Eggerthella lenta, Clostridium scindens, and three microbial genes across tubular adenoma, serrated polyp, and polyp-free cases. Conclusion: By directly sampling the colon mucosa and distinguishing between the different developmental pathways of colorectal cancer, this study helps characterize potential mechanistic targets and diagnostic biomarkers for serrated carcinogenesis. This research also provides insight into multiple microbiome sampling strategies by assessing each methods practicality and effect on microbial community composition.

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

2017 ◽  
Author(s):  
Ce Yuan ◽  
Michael Burns ◽  
Subbaya Subramanian ◽  
Ran Blekhman
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiome ◽  
Normal Tissue ◽  
Microbial Community Composition ◽  
Taxonomic Composition ◽  
Integrated Analysis ◽  
Tissue Samples ◽  
Microbiome Composition ◽  
Normal Tissues ◽  
Mirnas Expression

AbstractBackgroundAlthough 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 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 miRNAs expression in human CRC tumor and normal tissues and the microbiome composition associated with these same tissues.MethodWe sequenced the small RNAs from patient-matched tumor and normal tissue samples collected from 44 human CRC patients performed an integrated analysis with microbiome taxonomic composition data from these same samples. We then interrogated the functions of the bacteria correlated with miRNAs that were differentially expressed (DE) between tumor and matched normal tissues, as well as the functions of miRNAs correlated with bacterial taxa that have been previously associated with CRC, including Fusobacterium, Providencia, Bacteroides, Akkermansia, Roseburia, Porphyromonas, and Peptostreptococcus.ResultsWe identified 76 miRNAs as DE between CRC and normal tissue, including known oncogenic miRNAs miR-182, miR-503, and miR-17∼92. These DE miRNAs were correlated with the relative abundance 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 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.ConclusionsOur work characterized a global relationship between microbial community composition and miRNA expression in human CRC tissues. Our results support a role for miRNAs in mediating a bi-directional host-microbiome interaction in CRC. In addition, we highlight sets of potentially interacting microbes and host miRNAs, suggesting several pathways that can be targeted via future therapies.

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 Immune Gene Expression Covaries with Gut Microbiome Composition in Stickleback

mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Lauren E. Fuess ◽  
Stijn den Haan ◽  
Fei Ling ◽  
Jesse N. Weber ◽  
Natalie C. Steinel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microbial Communities ◽  
Gut Microbiome ◽  
Alpha Diversity ◽  
Host Immunity ◽  
Host Gene ◽  
Microbiota Composition ◽  
Host Gene Expression ◽  
Microbiome Composition ◽  
Immune Genes

ABSTRACT Commensal microbial communities have immense effects on their vertebrate hosts, contributing to a number of physiological functions, as well as host fitness. In particular, host immunity is strongly linked to microbiota composition through poorly understood bi-directional links. Gene expression may be a potential mediator of these links between microbial communities and host function. However, few studies have investigated connections between microbiota composition and expression of host immune genes in complex systems. Here, we leverage a large study of laboratory-raised fish from the species Gasterosteus aculeatus (three-spined stickleback) to document correlations between gene expression and microbiome composition. First, we examined correlations between microbiome alpha diversity and gene expression. Our results demonstrate robust positive associations between microbial alpha diversity and expression of host immune genes. Next, we examined correlations between host gene expression and abundance of microbial taxa. We identified 15 microbial families that were highly correlated with host gene expression. These families were all tightly correlated with host expression of immune genes and processes, falling into one of three categories—those positively correlated, negatively correlated, and neutrally related to immune processes. Furthermore, we highlight several important immune processes that are commonly associated with the abundance of these taxa, including both macrophage and B cell functions. Further functional characterization of microbial taxa will help disentangle the mechanisms of the correlations described here. In sum, our study supports prevailing hypotheses of intimate links between host immunity and gut microbiome composition. IMPORTANCE Here, we document associations between host gene expression and gut microbiome composition in a nonmammalian vertebrate species. We highlight associations between expression of immune genes and both microbiome diversity and abundance of specific microbial taxa. These findings support other findings from model systems which have suggested that gut microbiome composition and host immunity are intimately linked. Furthermore, we demonstrate that these correlations are truly systemic; the gene expression detailed here was collected from an important fish immune organ (the head kidney) that is anatomically distant from the gut. This emphasizes the systemic impact of connections between gut microbiota and host immune function. Our work is a significant advancement in the understanding of immune-microbiome links in nonmodel, natural systems.

Diagnostic, prognostic, and therapeutic value of miR-148b in human cancers

2021 ◽  
Vol 21 ◽  
Author(s):  
Afsane Bahrami ◽  
Gordon A. Ferns
Keyword(s):  
Gene Expression ◽  
Tumor Suppressor ◽  
Noncoding Rna ◽  
Clinical Importance ◽  
Aberrant Expression ◽  
Rna Molecules ◽  
Small Noncoding Rna ◽  
Human Cancers ◽  
Therapeutic Value ◽  
Cancer Types

: MicroRNAs (miRs) is a class of conserved, small, noncoding RNA molecules which modulate gene expression post-transcriptionally. miR-148b is a member of miR-148/152 family generally known to be a tumor suppressor via its affect on different signaling pathways and regulatory genes. Aberrant expression of miR-148b has recently been shown to be responsible for tumorigenesis for several different cancer types. This review discusses the current evidences regarding the involvement of miR-148b expression in human cancers and its potential clinical importance for tumor diagnosis, prognosis, and therapeutics.

Underdevelopment of the gut microbiota and bacteria species as non-invasive markers of prediction in children with autism spectrum disorder

Gut ◽  
2021 ◽  
pp. gutjnl-2020-324015
Author(s):  
Yating Wan ◽  
Tao Zuo ◽  
Zhilu Xu ◽  
Fen Zhang ◽  
Hui Zhan ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Chinese Children ◽  
Chronological Age ◽  
Microbiome Composition ◽  
Children With Asd ◽  
Faecal Microbiome

ObjectiveThe gut microbiota has been suggested to play a role in autism spectrum disorder (ASD). We postulate that children with ASD harbour an altered developmental profile of the gut microbiota distinct from that of typically developing (TD) children. Here, we aimed to characterise compositional and functional alterations in gut microbiome in association with age in children with ASD and to identify novel faecal bacterial markers for predicting ASD.DesignWe performed deep metagenomic sequencing in faecal samples of 146 Chinese children (72 ASD and 74 TD children). We compared gut microbial composition and functions between children with ASD and TD children. Candidate bacteria markers were identified and validated by metagenomic analysis. Gut microbiota development in relation to chronological age was assessed using random forest model.ResultsASD and chronological age had the most significant and largest impacts on children’s faecal microbiome while diet showed no correlation. Children with ASD had significant alterations in faecal microbiome composition compared with TD children characterised by increased bacterial richness (p=0.021) and altered microbiome composition (p<0.05). Five bacterial species were identified to distinguish gut microbes in ASD and TD children, with areas under the receiver operating curve (AUC) of 82.6% and 76.2% in the discovery cohort and validation cohort, respectively. Multiple neurotransmitter biosynthesis related pathways in the gut microbiome were depleted in children with ASD compared with TD children (p<0.05). Developing dynamics of growth-associated gut bacteria (age-discriminatory species) seen in TD children were lost in children with ASD across the early-life age spectrum.ConclusionsGut microbiome in Chinese children with ASD was altered in composition, ecological network and functionality compared with TD children. We identified novel bacterial markers for prediction of ASD and demonstrated persistent underdevelopment of the gut microbiota in children with ASD which lagged behind their respective age-matched peers.

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.

scholarly journals The Effects of Glucosamine and Chondroitin Sulfate on Gut Microbial Composition: A Systematic Review of Evidence from Animal and Human Studies

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 294 ◽  
Author(s):  
Anna Shmagel ◽  
Ryan Demmer ◽  
Daniel Knights ◽  
Mary Butler ◽  
Lisa Langsetmo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Gut Microbiota ◽  
Chondroitin Sulfate ◽  
Gut Microbiome ◽  
Human Studies ◽  
Journal Articles ◽  
Microbial Composition ◽  
Microbiome Composition ◽  
Search Terms ◽  
Quality Evidence

Oral glucosamine sulfate (GS) and chondroitin sulfate (CS), while widely marketed as joint-protective supplements, have limited intestinal absorption and are predominantly utilized by gut microbiota. Hence the effects of these supplements on the gut microbiome are of great interest, and may clarify their mode of action, or explain heterogeneity in therapeutic responses. We conducted a systematic review of animal and human studies reporting the effects of GS or CS on gut microbial composition. We searched MEDLINE, EMBASE, and Scopus databases for journal articles in English from database inception until July 2018, using search terms microbiome, microflora, intestinal microbiota/flora, gut microbiota/flora and glucosamine or chondroitin. Eight original articles reported the effects of GS or CS on microbiome composition in adult humans (four articles) or animals (four articles). Studies varied significantly in design, supplementation protocols, and microbiome assessment methods. There was moderate-quality evidence for an association between CS exposure and increased abundance of genus Bacteroides in the murine and human gut, and low-quality evidence for an association between CS exposure and an increase in Desulfovibrio piger species, an increase in Bacteroidales S24-7 family, and a decrease in Lactobacillus. We discuss the possible metabolic implications of these changes for the host. For GS, evidence of effects on gut microbiome was limited to one low-quality study. This review highlights the importance of considering the potential influence of oral CS supplements on gut microbiota when evaluating their effects and safety for the host.

scholarly journals Exosomal miRNA: Small Molecules, Big Impact in Colorectal Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Valentin Vautrot ◽  
Gaëtan Chanteloup ◽  
Mohammed Elmallah ◽  
Marine Cordonnier ◽  
François Aubin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Biology ◽  
Noncoding Rna ◽  
Cell Types ◽  
Response To Therapy ◽  
Bioactive Molecules ◽  
Premetastatic Niche ◽  
Rna Molecules ◽  
Small Noncoding Rna ◽  
Exosomal Mirna

Colorectal cancer (CRC) is one of the major causes of cancer-related deaths worldwide. Tumor microenvironment (TME) contains many cell types including stromal cells, immune cells, and endothelial cells. The TME modulation explains the heterogeneity of response to therapy observed in patients. In this context, exosomes are emerging as major contributors in cancer biology. Indeed, exosomes are implicated in tumor proliferation, angiogenesis, invasion, and premetastatic niche formation. They contain bioactive molecules such as proteins, lipids, and RNAs. More recently, many studies on exosomes have focused on miRNAs, small noncoding RNA molecules able to influence protein expression. In this review, we describe miRNAs transported by exosomes in the context of CRC and discuss their influence on TME and their potential as circulating biomarkers. This overview underlines emerging roles for exosomal miRNAs in cancer research for the near future.

scholarly journals The Role of the Gut Microbiome in Colorectal Cancer

2018 ◽  
Vol 31 (03) ◽  
pp. 192-198 ◽  
Author(s):  
Grace Chen
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Microbial Community ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Intestinal Health ◽  
Genotoxic Effects ◽  
Bacterial Populations ◽  
Health And Disease

AbstractThere is increasing evidence that the gut microbiome, which consists of trillions of microbes representing over 1,000 species of bacteria with over 3 million genes, significantly impacts intestinal health and disease. The gut microbiota not only is capable of promoting intestinal homeostasis and antitumor responses but can also contribute to chronic dysregulated inflammation as well as have genotoxic effects that lead to carcinogenesis. Whether the gut microbiota maintains health or promotes colon cancer may ultimately depend on the composition of the gut microbiome and the balance within the microbial community of protective and detrimental bacterial populations. Disturbances in the normal balanced state of a healthful microbiome, known as dysbiosis, have been observed in patients with colorectal cancer (CRC); however, whether these alterations precede and cause CRC remains to be determined. Nonetheless, studies in mice strongly suggest that the gut microbiota can modulate susceptibility to CRC, and therefore may serve as both biomarkers and therapeutic targets.

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