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Gut Jun 2018We aimed to characterise the microbial changes associated with histological stages of gastric tumourigenesis.
OBJECTIVES
We aimed to characterise the microbial changes associated with histological stages of gastric tumourigenesis.
DESIGN
We performed 16S rRNA gene analysis of gastric mucosal samples from 81 cases including superficial gastritis (SG), atrophic gastritis (AG), intestinal metaplasia (IM) and gastric cancer (GC) from Xi'an, China, to determine mucosal microbiome dysbiosis across stages of GC. We validated the results in mucosal samples of 126 cases from Inner Mongolia, China.
RESULTS
We observed significant mucosa microbial dysbiosis in IM and GC subjects, with significant enrichment of 21 and depletion of 10 bacterial taxa in GC compared with SG (q<0.05). Microbial network analysis showed increasing correlation strengths among them with disease progression (p<0.001). Five GC-enriched bacterial taxa whose species identifications correspond to , , , and had significant centralities in the GC ecological network (p<0.05) and classified GC from SG with an area under the receiver-operating curve (AUC) of 0.82. Moreover, stronger interactions among gastric microbes were observed in -negative samples compared with -positive samples in SG and IM. The fold changes of selected bacteria, and strengths of their interactions were successfully validated in the Inner Mongolian cohort, in which the five bacterial markers distinguished GC from SG with an AUC of 0.81.
CONCLUSIONS
In addition to microbial compositional changes, we identified differences in bacterial interactions across stages of gastric carcinogenesis. The significant enrichments and network centralities suggest potentially important roles of , , , and in GC progression.
Topics: Adult; Aged; Aged, 80 and over; Area Under Curve; Carcinogenesis; Cell Transformation, Neoplastic; China; Dysbiosis; Female; Gastric Mucosa; Humans; Male; Microbiota; Middle Aged; RNA, Ribosomal, 16S; Stomach; Stomach Neoplasms; Young Adult
PubMed: 28765474
DOI: 10.1136/gutjnl-2017-314281 -
Gut Microbes 2023Colorectal cancer (CRC) is the third most common malignant tumor worldwide. The incidence and mortality rates of CRC have been increasing in China, possibly due to... (Review)
Review
Colorectal cancer (CRC) is the third most common malignant tumor worldwide. The incidence and mortality rates of CRC have been increasing in China, possibly due to economic development, lifestyle, and dietary changes. Evidence suggests that gut microbiota plays an essential role in the tumorigenesis of CRC. Gut dysbiosis, specific pathogenic microbes, metabolites, virulence factors, and microbial carcinogenic mechanisms contribute to the initiation and progression of CRC. Gut microbiota biomarkers have potential translational applications in CRC screening and early diagnosis. Gut microbiota-related interventions could improve anti-tumor therapy's efficacy and severe intestinal toxic effects. Chinese researchers have made many achievements in the relationship between gut microbiota and CRC, although some challenges remain. This review summarizes the current evidence from China on the role of gut microbiota in CRC, mainly including the gut microbiota characteristics, especially and , which have been identified to be enriched in CRC patients; microbial pathogens such as and enterotoxigenic , and , which Chinese scientists have extensively studied; diagnostic biomarkers especially ; therapeutic effects, including microecological agents represented by certain strains, fecal microbiota transplantation, and traditional Chinese medicines such as Berberine and Curcumin. More efforts should be focused on exploring the underlying mechanisms of microbial pathogenesis of CRC and providing novel gut microbiota-related therapeutic and preventive strategies.
Topics: Humans; Gastrointestinal Microbiome; Colorectal Neoplasms; Carcinogenesis; China; Biomarkers
PubMed: 37482657
DOI: 10.1080/19490976.2023.2236364 -
Cancer Medicine Sep 2020Bacteria identified in the oral cavity are highly complicated. They include approximately 1000 species with a diverse variety of commensal microbes that play crucial... (Review)
Review
Bacteria identified in the oral cavity are highly complicated. They include approximately 1000 species with a diverse variety of commensal microbes that play crucial roles in the health status of individuals. Epidemiological studies related to molecular pathology have revealed that there is a close relationship between oral microbiota and tumor occurrence. Oral microbiota has attracted considerable attention for its role in in-situ or distant tumor progression. Anaerobic oral bacteria with potential pathogenic abilities, especially Fusobacterium nucleatum and Porphyromonas gingivalis, are well studied and have close relationships with various types of carcinomas. Some aerobic bacteria such as Parvimonas are also linked to tumorigenesis. Moreover, human papillomavirus, oral fungi, and parasites are closely associated with oropharyngeal carcinoma. Microbial dysbiosis, colonization, and translocation of oral microbiota are necessary for implementation of carcinogenic functions. Various underlying mechanisms of oral microbiota-induced carcinogenesis have been reported including excessive inflammatory reaction, immunosuppression of host, promotion of malignant transformation, antiapoptotic activity, and secretion of carcinogens. In this review, we have systemically described the impact of oral microbial abnormalities on carcinogenesis and the future directions in this field for bringing in new ideas for effective prevention of tumors.
Topics: Alphapapillomavirus; Bacteria, Aerobic; Bacteria, Anaerobic; Bacterial Translocation; Cell Transformation, Neoplastic; Disease Progression; Dysbiosis; Firmicutes; Fungi; Fusobacterium nucleatum; Humans; Immune Tolerance; Microbiota; Mouth; Neoplasms; Oropharyngeal Neoplasms; Porphyromonas gingivalis
PubMed: 32638533
DOI: 10.1002/cam4.3206 -
Oncogene Sep 2022Large-scale fecal shotgun metagenomic sequencing revealed the high abundance of Parvimonas micra in colorectal cancer (CRC) patients. We investigated the role and...
Large-scale fecal shotgun metagenomic sequencing revealed the high abundance of Parvimonas micra in colorectal cancer (CRC) patients. We investigated the role and clinical significance of P. micra in colorectal tumorigenesis. The abundance of P. micra was examined in 309 fecal samples and 165 colon biopsy tissues of CRC patients and healthy subjects. P. micra was significantly enriched in fecal samples from 128 CRC patients compared to 181 healthy subjects (P < 0.0001); and in colon tissue biopsies from 52 CRC patients compared to 61 healthy subjects (P < 0.0001). Multivariate analysis showed that P. micra is an independent risk factor of poor survival in CRC patients (Hazard Ratio: 1.93). P. micra strain was isolated from feces of a CRC patient. Apc mice gavaged with P. micra showed significantly higher tumor burden and tumor load (both P < 0.01). Consistently, gavage of P. micra significantly promoted colonocyte proliferation in conventional mice, which was further confirmed by germ-free mice. P. micra colonization up-regulated genes involved in cell proliferation, stemness, angiogenesis and invasiveness/metastasis; and enhanced Th17 cells infiltration and expression of Th17 cells-secreted cytokines (Il-17, Il-22, and Il-23) in the colon of Apc, conventional and germ-free mice. P. micra-conditioned medium significantly promoted the differentiation of CD4 T cells to Th17 cells (IL-17CD4 phenotype) and enhanced the oncogenic Wnt signaling pathway. In conclusion, P. micra promoted colorectal tumorigenesis in mice by inducing colonocyte proliferation and altering Th17 immune response. P. micra may act as a prognostic biomarker for poor survival of CRC patients.
Topics: Animals; Carcinogenesis; Cell Proliferation; Colorectal Neoplasms; Firmicutes; Gene Expression Regulation, Neoplastic; Humans; Interleukin-17; Mice
PubMed: 35882981
DOI: 10.1038/s41388-022-02395-7 -
Healthcare (Basel, Switzerland) Sep 2022(), a bacterium that colonizes the gastrointestinal tract, is often isolated from periodontitis and abscesses as part of a complex bacterial infection. However, reports... (Review)
Review
(), a bacterium that colonizes the gastrointestinal tract, is often isolated from periodontitis and abscesses as part of a complex bacterial infection. However, reports of monobacterium infections due to are limited. Here, we report a case of monobacterial bacteremia caused by with the aim of identifying the source of the invasion and clarifying the clinical features. A 54-year-old patient presented with bacteremia due to and with an oral invasion that we suspected resulted from prior dental treatment. Using PubMed and Google Scholar databases, we undertook a systematic review of monobacteremia caused by . We identified 26 patients (mean age, 70.15 years) in our systematic review. bacteremia and its associated phenotypes were most frequently identified in spinal discitis, followed by epidural and lumbar abscesses, and infective endocarditis. The major risk factors were malignancy, diabetes mellitus, and post-arthroplasty. When is detected in blood cultures, evaluation and intervention for oral contamination may be indicated.
PubMed: 36141340
DOI: 10.3390/healthcare10091727 -
, an oral pathobiont associated with colorectal cancer, epigenetically reprograms human colonocytes.Gut Microbes Dec 2023Recently, an intestinal dysbiotic microbiota with enrichment in oral cavity bacteria has been described in colorectal cancer (CRC) patients. Here, we characterize and...
Recently, an intestinal dysbiotic microbiota with enrichment in oral cavity bacteria has been described in colorectal cancer (CRC) patients. Here, we characterize and investigate one of these oral pathobionts, the Gram-positive anaerobic coccus . We identified two phylotypes (A and B) exhibiting different phenotypes and adhesion capabilities. We observed a strong association of phylotype A with CRC, with its higher abundance in feces and in tumoral tissue compared with the normal homologous colonic mucosa, which was associated with a distinct methylation status of patients. By developing an hypoxic co-culture system of human primary colonic cells with anaerobic bacteria, we show that phylotype A alters the DNA methylation profile promoters of key tumor-suppressor genes, oncogenes, and genes involved in epithelial-mesenchymal transition. In colonic mucosa of CRC patients carrying phylotype A, we found similar DNA methylation alterations, together with significant enrichment of differentially expressed genes in pathways involved in inflammation, cell adhesion, and regulation of actin cytoskeleton, providing evidence of possible role in the carcinogenic process.
Topics: Humans; Gastrointestinal Microbiome; Firmicutes; Bacteria; Colorectal Neoplasms
PubMed: 37842920
DOI: 10.1080/19490976.2023.2265138 -
Microbiome Apr 2018Alterations of gut microbiota are associated with colorectal cancer (CRC) in different populations and several bacterial species were found to contribute to the...
BACKGROUND
Alterations of gut microbiota are associated with colorectal cancer (CRC) in different populations and several bacterial species were found to contribute to the tumorigenesis. The potential use of gut microbes as markers for early diagnosis has also been reported. However, cohort specific noises may distort the structure of microbial dysbiosis in CRC and lead to inconsistent results among studies. In this regard, our study targeted at exploring changes in gut microbiota that are universal across populations at species level.
RESULTS
Based on the combined analysis of 526 metagenomic samples from Chinese, Austrian, American, and German and French cohorts, seven CRC-enriched bacteria (Bacteroides fragilis, Fusobacterium nucleatum, Porphyromonas asaccharolytica, Parvimonas micra, Prevotella intermedia, Alistipes finegoldii, and Thermanaerovibrio acidaminovorans) have been identified across populations. The seven enriched bacterial markers classified cases from controls with an area under the receiver-operating characteristics curve (AUC) of 0.80 across the different populations. Abundance correlation analysis demonstrated that CRC-enriched and CRC-depleted bacteria respectively formed their own mutualistic networks, in which the latter was disjointed in CRC. The CRC-enriched bacteria have been found to be correlated with lipopolysaccharide and energy biosynthetic pathways.
CONCLUSIONS
Our study identified potential diagnostic bacterial markers that are robust across populations, indicating their potential universal use for non-invasive CRC diagnosis. We also elucidated the ecological networks and functional capacities of CRC-associated microbiota.
Topics: Aged; Bacteria; Cell Transformation, Neoplastic; Colorectal Neoplasms; Computational Biology; Female; Gastrointestinal Microbiome; Gene Ontology; Humans; Male; Metagenome; Metagenomics; Middle Aged
PubMed: 29642940
DOI: 10.1186/s40168-018-0451-2 -
BMJ Case Reports Sep 2022We present a rare case of destructive osteomyelitis of the sternum caused by and A previously healthy female patient in her 40s presented to the emergency department...
We present a rare case of destructive osteomyelitis of the sternum caused by and A previously healthy female patient in her 40s presented to the emergency department due to a spontaneous rupture of an abscess located to the chest wall. Imaging confirmed abscess formation with osteomyelitis of the sternum. Emergent surgical debridement was performed, blood and bone cultures were taken and the patient received antibiotic treatment. Cultures of the bone and deep tissue revealed infection with and , both being members of the oral flora and associated with chronic periodontitis. Receiving targeted antibiotic treatment, our patient made a quick recovery. After treatment of the osteomyelitis, our patient was referred to the dentist where chronic periodontitis could be confirmed. Invasive infections with and are rare. Investigation of a dental origin is crucial to prevent recurrent infections.
Topics: Abscess; Anti-Bacterial Agents; Campylobacter rectus; Chronic Periodontitis; Female; Firmicutes; Humans; Osteomyelitis; Peptostreptococcus
PubMed: 36137645
DOI: 10.1136/bcr-2022-250886 -
Bioscience Reports Jun 2023The gut microbiota Parvimonas micra has been found to be enriched in gut mucosal tissues and fecal samples of colorectal cancer (CRC) patients compared with non-CRC...
The gut microbiota Parvimonas micra has been found to be enriched in gut mucosal tissues and fecal samples of colorectal cancer (CRC) patients compared with non-CRC controls. In the present study, we investigated the tumorigenic potential of P. micra and its regulatory pathways in CRC using HT-29, a low-grade CRC intestinal epithelial cell. For every P. micra-HT-29 interaction assay, HT-29 was co-cultured anaerobically with P. micra at an MOI of 100:1 (bacteria: cells) for 2 h. We found that P. micra increased HT-29 cell proliferation by 38.45% (P=0.008), with the highest wound healing rate at 24 h post-infection (P=0.02). In addition, inflammatory marker expression (IL-5, IL-8, CCL20, and CSF2) was also significantly induced. Shotgun proteomics profiling analysis revealed that P. micra affects the protein expression of HT-29 (157 up-regulated and 214 down-regulated proteins). Up-regulation of PSMB4 protein and its neighbouring subunits revealed association of the ubiquitin-proteasome pathway (UPP) in CRC carcinogenesis; whereas down-regulation of CUL1, YWHAH, and MCM3 signified cell cycle dysregulation. Moreover, 22 clinically relevant epithelial-mesenchymal transition (EMT)-markers were expressed in HT-29 infected with P. micra. Overall, the present study elucidated exacerbated oncogenic properties of P. micra in HT-29 via aberrant cell proliferation, enhanced wound healing, inflammation, up-regulation of UPPs, and activation of EMT pathways.
Topics: Humans; Colorectal Neoplasms; HT29 Cells; Cell Proliferation; Inflammation; Epithelial-Mesenchymal Transition; Cell Movement; Proteasome Endopeptidase Complex
PubMed: 37218575
DOI: 10.1042/BSR20230609 -
Journal of Experimental & Clinical... Jan 2023Colorectal cancer (CRC) is the third most common cancer in the world, and a strong relationship exists between CRC and gut microbiota, which affects the occurrence,...
BACKGROUND
Colorectal cancer (CRC) is the third most common cancer in the world, and a strong relationship exists between CRC and gut microbiota, which affects the occurrence, development, and metastasis of cancer. Bioinformatics-based analyses revealed that the abundance of Parvimonas micra (P. micra) in the feces of patients with cancer is significantly higher than that in healthy people. Therefore, an important relationship may exist between P. micra and CRC.
METHODS
We first confirmed that P. micra can promote the proliferation of cell lines through cell experiments and mouse models. Then we selected the signaling pathways and content of exosomes to promote the development of CRC by transcriptomics and microRNA sequencing. Finally, we confirmed that P. micra promoted CRC development through miR-218-5p/Ras/ERK/c-Fos pathway through the in vivo and in vitro experiments.
RESULTS
First, it was confirmed by in vitro and in vivo experiments that P. micra can promote the development of CRC. Transcriptome analysis after the coincubation of bacteria and cells revealed that P. micra promoted cell proliferation by activating the Ras/ERK/c-Fos pathway. Furthermore, microRNA sequencing analysis of the cells and exosomes showed that miR-218-5p and protein tyrosine phosphatase receptor R (PTPRR) were the key factors involved in activating the Ras/ERK/c-Fos pathway, and the miR-218-5p inhibitor was used to confirm the role of microRNA in xenograft mice.
CONCLUSION
This experiment confirmed that P. micra promoted the development of CRC by upregulating miR-218-5p expression in cells and exosomes, inhibiting PTPRR expression, and ultimately activating the Ras/ERK/c-Fos signaling pathway.
Topics: Animals; Humans; Mice; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Gene Expression Regulation, Neoplastic; MicroRNAs; Signal Transduction; Firmicutes
PubMed: 36627634
DOI: 10.1186/s13046-022-02572-2