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Frontiers in Immunology 2020The intestinal microbiota, composed of a large population of microorganisms, is often considered a "forgotten organ" in human health and diseases. Increasing evidence... (Review)
Review
The intestinal microbiota, composed of a large population of microorganisms, is often considered a "forgotten organ" in human health and diseases. Increasing evidence indicates that dysbiosis of the intestinal microbiota is closely related to colorectal cancer (CRC). The roles for intestinal microorganisms that initiated and facilitated the CRC process are becoming increasingly clear. Hypothesis models have been proposed to illustrate the complex relationship between the intestinal microbiota and CRC. Recent studies have identified , enterotoxigenic , , , , and as CRC candidate pathogens. In this review, we summarized the mechanisms involved in microbiota-related colorectal carcinogenesis, including inflammation, pathogenic bacteria, and their virulence factors, genotoxins, oxidative stress, bacterial metabolites, and biofilm. We also described the clinical values of intestinal microbiota and novel strategies for preventing and treating CRC.
Topics: Adenocarcinoma; Animals; Bacteria; Biodiversity; Biofilms; Carcinogenesis; Cell Transformation, Neoplastic; Colorectal Neoplasms; Diet; Gastrointestinal Microbiome; Genes, APC; Humans; Inflammation; Mice; Models, Biological; Mutagens; Neoplastic Syndromes, Hereditary; Oxidative Stress; Rats; Virulence
PubMed: 33329610
DOI: 10.3389/fimmu.2020.615056 -
Cell Host & Microbe Mar 2023The intestinal microbiota plays an important role in colorectal cancer (CRC) progression. However, the effect of tissue-resident commensal bacteria on CRC immune...
The intestinal microbiota plays an important role in colorectal cancer (CRC) progression. However, the effect of tissue-resident commensal bacteria on CRC immune surveillance remains poorly understood. Here, we analyzed the intratissue bacteria from CRC patient colon tissues. We found that the commensal bacteria belonging to the Lachnospiraceae family, including Ruminococcus gnavus (Rg), Blautia producta (Bp), and Dorea formicigenerans (Df), were enriched in normal tissues, while Fusobacterium nucleatum (Fn) and Peptostreptococcus anaerobius (Pa) were abundant in tumor tissues. Tissue-resident Rg and Bp reduced colon tumor growth and promoted the activation of CD8 T cells in immunocompetent mice. Mechanistically, intratissue Rg and Bp degraded lyso-glycerophospholipids that inhibited CD8 T cell activity and maintained the immune surveillance function of CD8 T cells. Lyso-glycerophospholipids alone promoted tumor growth that was abrogated with Rg and Bp injection. Collectively, intratissue Lachnospiraceae family bacteria facilitate the immune surveillance function of CD8 T cells and control colorectal cancer progression.
Topics: Animals; Mice; Colorectal Neoplasms; CD8-Positive T-Lymphocytes; Carcinogenesis; Colonic Neoplasms; Fusobacterium nucleatum
PubMed: 36893736
DOI: 10.1016/j.chom.2023.01.013 -
Clinical Microbiology Reviews Apr 2016Bacterial vaginosis (BV) is the most commonly reported microbiological syndrome among women of childbearing age. BV is characterized by a shift in the vaginal flora from... (Review)
Review
Bacterial vaginosis (BV) is the most commonly reported microbiological syndrome among women of childbearing age. BV is characterized by a shift in the vaginal flora from the dominant Lactobacillus to a polymicrobial flora. BV has been associated with a wide array of health issues, including preterm births, pelvic inflammatory disease, increased susceptibility to HIV infection, and other chronic health problems. A number of potential microbial pathogens, singly and in combinations, have been implicated in the disease process. The list of possible agents continues to expand and includes members of a number of genera, including Gardnerella, Atopobium, Prevotella, Peptostreptococcus, Mobiluncus, Sneathia, Leptotrichia, Mycoplasma, and BV-associated bacterium 1 (BVAB1) to BVAB3. Efforts to characterize BV using epidemiological, microscopic, microbiological culture, and sequenced-based methods have all failed to reveal an etiology that can be consistently documented in all women with BV. A careful analysis of the available data suggests that what we term BV is, in fact, a set of common clinical signs and symptoms that can be provoked by a plethora of bacterial species with proinflammatory characteristics, coupled to an immune response driven by variability in host immune function.
Topics: Bacteria; DNA, Bacterial; Female; Humans; Microbiota; Vaginosis, Bacterial
PubMed: 26864580
DOI: 10.1128/CMR.00075-15 -
Seminars in Cancer Biology Nov 2022Colorectal cancer (CRC) is one of the most common malignancies worldwide. The main risk factors for CRC are family history of colon or rectal cancer, familial polyposis... (Review)
Review
Colorectal cancer (CRC) is one of the most common malignancies worldwide. The main risk factors for CRC are family history of colon or rectal cancer, familial polyposis syndrome or hereditary nonpolyposis, and chronic inflammatory bowel diseases (ulcerative colitis and Crohn's disease). Recent studies show that the gastrointestinal microbiota play a significant role in colorectal carcinogenesis. In this review we present the microorganisms, whose influence on the development of CRC has been proven: Bacteroides fragilis, Clostridioides and Clostridium spp., Enterococcus faecalis, Escherichia coli, Fusobacterium nucleatum, Helicobacter pylori, Peptostreptococcus anaerobius, Streptococcus bovis group, and sulfate-reducing bacteria. Moreover, the carcinogenic mechanisms of action mediated by the above bacteria are laid out.
Topics: Humans; Carcinogens; Colorectal Neoplasms; Fusobacterium nucleatum; Carcinogenesis; Microbiota
PubMed: 35090978
DOI: 10.1016/j.semcancer.2022.01.004 -
Microbiology Spectrum Aug 2022Colorectal cancer (CRC) is the second leading cause of cancer mortality worldwide. The dysbiotic gut microbiota and its metabolite secretions play a significant role in... (Meta-Analysis)
Meta-Analysis
Colorectal cancer (CRC) is the second leading cause of cancer mortality worldwide. The dysbiotic gut microbiota and its metabolite secretions play a significant role in CRC development and progression. In this study, we identified microbial and metabolic biomarkers applicable to CRC using a meta-analysis of metagenomic datasets from diverse geographical regions. We used LEfSe, random forest (RF), and co-occurrence network methods to identify microbial biomarkers. Geographic dataset-specific markers were identified and evaluated using area under the ROC curve (AUC) scores and random effect size. Co-occurrence networks analysis showed a reduction in the overall microbial associations and the presence of oral pathogenic microbial clusters in CRC networks. Analysis of predicted metabolites from CRC datasets showed the enrichment of amino acids, cadaverine, and creatine in CRC, which were positively correlated with CRC-associated microbes (Peptostreptococcus stomatis, Gemella morbillorum, Bacteroides fragilis, spp., Fusobacterium nucleatum, Solobacterium moorei, and Clostridium symbiosum), and negatively correlated with control-associated microbes. Conversely, butyrate, nicotinamide, choline, tryptophan, and 2-hydroxybutanoic acid showed positive correlations with control-associated microbes ( < 0.05). Overall, our study identified a set of global CRC biomarkers that are reproducible across geographic regions. We also reported significant differential metabolites and microbe-metabolite interactions associated with CRC. This study provided significant insights for further investigations leading to the development of noninvasive CRC diagnostic tools and therapeutic interventions. Several studies showed associations between gut dysbiosis and CRC. Yet, the results are not conclusive due to cohort-specific associations that are influenced by genomic, dietary, and environmental stimuli and associated reproducibility issues with various analysis approaches. Emerging evidence suggests the role of microbial metabolites in modulating host inflammation and DNA damage in CRC. However, the experimental validations have been hindered by cost, resources, and cumbersome technical expertise required for metabolomic investigations. In this study, we performed a meta-analysis of CRC microbiota data from diverse geographical regions using multiple methods to achieve reproducible results. We used a computational approach to predict the metabolomic profiles using existing CRC metagenomic datasets. We identified a reliable set of CRC-specific biomarkers from this analysis, including microbial and metabolite markers. In addition, we revealed significant microbe-metabolite associations through correlation analysis and microbial gene families associated with dysregulated metabolic pathways in CRC, which are essential in understanding the vastly sporadic nature of CRC development and progression.
Topics: Biomarkers; Colorectal Neoplasms; Dysbiosis; Gastrointestinal Microbiome; Humans; Reproducibility of Results
PubMed: 35766483
DOI: 10.1128/spectrum.00013-22 -
Frontiers in Cellular and Infection... 2019The oral microbiota plays an important role in the human microbiome and human health, and imbalances between microbes and their hosts can lead to oral and systemic...
The oral microbiota plays an important role in the human microbiome and human health, and imbalances between microbes and their hosts can lead to oral and systemic diseases and chronic inflammation, which is usually caused by bacteria and contributes to cancer. There may be a relationship between oral bacteria and oral squamous cell carcinoma (OSCC); however, this relationship has not been thoroughly characterized. Therefore, in this study, we compared the microbiota compositions between tumor sites and opposite normal tissues in buccal mucosal of 50 patients with OSCC using the 16S rDNA sequencing. Richness and diversity of bacteria were significantly higher in tumor sites than in the control tissues. Cancer tissues were enriched in six families (, and ) and 13 genera, including and . At the species level, the abundances of , and another five species were significantly increased, suggesting a potential association between these bacteria and OSCC. Furthermore, the functional prediction revealed that genes involved in bacterial chemotaxis, flagellar assembly and lipopolysaccharide (LPS) biosynthesis which are associated with various pathological processes, were significantly increased in the OSCC group. Overall, oral bacterial profiles showed significant difference between cancer sites and normal tissue of OSCC patients, which might be onsidered diagnostic markers and treatment targets. Our study has been registered in the Chinese clinical trial registry (ChiCTR1900025253, http://www.chictr.org.cn/index.aspx).
Topics: Bacteria; Carcinoma, Squamous Cell; DNA, Ribosomal; Female; Fusobacterium nucleatum; Humans; Lipopolysaccharides; Male; Microbiota; Middle Aged; Mouth; Mouth Mucosa; Peptostreptococcus; Prevotella intermedia; RNA, Ribosomal, 16S
PubMed: 32010645
DOI: 10.3389/fcimb.2019.00476 -
Gut Jan 2017To evaluate the potential for diagnosing colorectal cancer (CRC) from faecal metagenomes.
OBJECTIVE
To evaluate the potential for diagnosing colorectal cancer (CRC) from faecal metagenomes.
DESIGN
We performed metagenome-wide association studies on faecal samples from 74 patients with CRC and 54 controls from China, and validated the results in 16 patients and 24 controls from Denmark. We further validated the biomarkers in two published cohorts from France and Austria. Finally, we employed targeted quantitative PCR (qPCR) assays to evaluate diagnostic potential of selected biomarkers in an independent Chinese cohort of 47 patients and 109 controls.
RESULTS
Besides confirming known associations of Fusobacterium nucleatum and Peptostreptococcus stomatis with CRC, we found significant associations with several species, including Parvimonas micra and Solobacterium moorei. We identified 20 microbial gene markers that differentiated CRC and control microbiomes, and validated 4 markers in the Danish cohort. In the French and Austrian cohorts, these four genes distinguished CRC metagenomes from controls with areas under the receiver-operating curve (AUC) of 0.72 and 0.77, respectively. qPCR measurements of two of these genes accurately classified patients with CRC in the independent Chinese cohort with AUC=0.84 and OR of 23. These genes were enriched in early-stage (I-II) patient microbiomes, highlighting the potential for using faecal metagenomic biomarkers for early diagnosis of CRC.
CONCLUSIONS
We present the first metagenomic profiling study of CRC faecal microbiomes to discover and validate microbial biomarkers in ethnically different cohorts, and to independently validate selected biomarkers using an affordable clinically relevant technology. Our study thus takes a step further towards affordable non-invasive early diagnostic biomarkers for CRC from faecal samples.
Topics: Aged; Area Under Curve; Austria; Biomarkers, Tumor; Case-Control Studies; China; Cohort Studies; Colorectal Neoplasms; Denmark; Dysbiosis; Feces; Female; Firmicutes; France; Fusobacterium nucleatum; Gastrointestinal Microbiome; Genome-Wide Association Study; Humans; Male; Metagenomics; Middle Aged; Peptostreptococcus; ROC Curve
PubMed: 26408641
DOI: 10.1136/gutjnl-2015-309800 -
Nature Microbiology Dec 2019Emerging evidence implicates a role of the gut microbiota in colorectal cancer (CRC). Peptostreptococcus anaerobius (P. anaerobius) is an anaerobic bacterium selectively...
Emerging evidence implicates a role of the gut microbiota in colorectal cancer (CRC). Peptostreptococcus anaerobius (P. anaerobius) is an anaerobic bacterium selectively enriched in the faecal and mucosal microbiota from patients with CRC, but its causative role and molecular mechanism in promoting tumorigenesis remain unestablished. We demonstrate that P. anaerobius adheres to the CRC mucosa and accelerates CRC development in Apc mice. In vitro assays and transmission electron microscopy revealed that P. anaerobius selectively adheres to CRC cell lines (HT-29 and Caco-2) compared to normal colonic epithelial cells (NCM460). We identified a P. anaerobius surface protein, putative cell wall binding repeat 2 (PCWBR2), which directly interacts with colonic cell lines via α/β integrin, a receptor frequently overexpressed in human CRC tumours and cell lines. Interaction between PCWBR2 and integrin α/β induces the activation of the PI3K-Akt pathway in CRC cells via phospho-focal adhesion kinase, leading to increased cell proliferation and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. NF-κB in turn triggers a pro-inflammatory response as indicated by increased levels of cytokines, such as interleukin-10 and interferon-γ in the tumours of P. anaerobius-treated Apc mice. Analyses of tumour-infiltrating immune cell populations in P. anaerobius-treated Apc mice revealed significant expansion of myeloid-derived suppressor cells, tumour-associated macrophages and granulocytic tumour-associated neutrophils, which are associated with chronic inflammation and tumour progression. Blockade of integrin α/β by RGDS peptide, small interfering RNA or antibodies all impair P. anaerobius attachment and abolish P. anaerobius-mediated oncogenic response in vitro and in vivo. Collectively, we show that P. anaerobius drives CRC via a PCWBR2-integrin α/β-PI3K-Akt-NF-κB signalling axis and identify the PCWBR2-integrin α/β axis as a potential therapeutic target for CRC.
Topics: Animals; Biotin; Caco-2 Cells; Carcinogenesis; Cell Proliferation; Cell Survival; Colon; Colorectal Neoplasms; Cytokines; Disease Models, Animal; Focal Adhesion Protein-Tyrosine Kinases; Gene Expression Profiling; Gene Knockdown Techniques; HT29 Cells; Humans; Integrin alpha2beta1; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Peptostreptococcus; Phosphatidylinositol 3-Kinases; Signal Transduction
PubMed: 31501538
DOI: 10.1038/s41564-019-0541-3 -
Scientific Reports Sep 2017Individual bacteria and shifts in microbiome composition are associated with human disease, including cancer. To unravel the connections underlying oral bacterial... (Clinical Trial)
Clinical Trial
Individual bacteria and shifts in microbiome composition are associated with human disease, including cancer. To unravel the connections underlying oral bacterial dysbiosis and oral squamous cell carcinoma (OSCC), cancer lesion samples and anatomically matched normal samples were obtained from the same patients. We then profiled the bacteria within OSCC lesion surface samples at the species level using next-generation sequencing to comprehensively investigate bacterial community composition and functional genes in these samples. Significantly greater bacterial diversity was observed in the cancer samples than in the normal samples. Compared with previous studies, we identified many more taxa demonstrating remarkably different distributions between the groups. In particular, a group of periodontitis-correlated taxa, including Fusobacterium, Dialister, Peptostreptococcus, Filifactor, Peptococcus, Catonella and Parvimonas, was significantly enriched in OSCC samples. Additionally, several operational taxonomic units (OTUs) associated with Fusobacterium were highly involved in OSCC and demonstrated good diagnostic power. Our study revealed drastic changes in surface bacterial communities of OSCC. The findings enrich knowledge of the association between oral bacterial communities and oral cancer.
Topics: Bacteria; Carcinoma, Squamous Cell; Female; Humans; Male; Microbiota; Middle Aged; Mouth Neoplasms
PubMed: 28924229
DOI: 10.1038/s41598-017-11779-9