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, 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 -
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 -
Environmental Microbiology Reports Aug 2023Recent advances in our understanding of microbiome composition at sites of inflammatory dysbiosis have triggered a substantial interest in a variety of historically... (Review)
Review
Recent advances in our understanding of microbiome composition at sites of inflammatory dysbiosis have triggered a substantial interest in a variety of historically understudied bacteria, especially among fastidious obligate anaerobes. A plethora of new evidence suggests that these microbes play outsized roles in establishing synergistic polymicrobial infections at many different sites in the human body. Parvimonas micra is a prime example of such an organism. Despite being almost completely uncharacterized at the genetic level, it is one of the few species commonly detected in abundance at multiple mucosal sites experiencing either chronic or acute inflammatory diseases, and more recently, it has been proposed as a discriminating biomarker for multiple types of malignancies. In the absence of disease, P. micra is commonly found in low abundance, typically residing within the oral cavity and gastrointestinal tract. P. micra exhibits the typical features of an inflammophilic organism, meaning its growth actually benefits from active inflammation and inflammatory tissue destruction. In this mini-review, we will describe our current understanding of this underappreciated but ubiquitous pathobiont, specifically focusing upon the role of P. micra in polymicrobial inflammatory dysbiosis and cancer as well as the key emerging questions regarding its pathobiology. Through this timely work, we highlight Parvimonas micra as a significant driver of disease and discuss its unique position at the crossroads of dysbiosis and cancer.
Topics: Humans; Dysbiosis; Firmicutes; Neoplasms; Gastrointestinal Tract
PubMed: 36999244
DOI: 10.1111/1758-2229.13153 -
Healthcare (Basel, Switzerland) Nov 2023Septic arthritis is a life-threatening rheumatological syndrome that is highly related to a patient's immune status and comorbidities, and although the most common...
Septic arthritis is a life-threatening rheumatological syndrome that is highly related to a patient's immune status and comorbidities, and although the most common clinical presentation is rapid-onset monoarthritis, it can also appear as subacute or chronic joint swelling. In these cases, differential diagnosis is more challenging, but early diagnosis and treatment is no less urgent to ensure a good global prognosis and the best outcome of the affected joint. Anaerobic microorganisms, such as , are an uncommon cause of septic arthritis (less than 5% of cases) but may be the cause of subacute arthritis. Knowledge about is important, as it is difficult to culture in the laboratory and generates a synovial fluid with atypical characteristics for septic arthritis so that, if not suspected, its diagnosis can be easily overlooked and underdiagnosed. We present the case of a 76-year-old woman with subacute arthritis of the left knee, describe the difficult diagnosis and treatment of its unexpected cause (), and review previously described cases, identifying the possible common comorbidities that may help clinicians easily find and treat this cause of subacute septic arthritis.
PubMed: 37958023
DOI: 10.3390/healthcare11212879 -
Respiratory Medicine Case Reports 2023is a gram-positive anaerobic coccus (GPAC) that colonizes the oral cavity and gastrointestinal tract. Recent advances in bacterial identification have confirmed the...
is a gram-positive anaerobic coccus (GPAC) that colonizes the oral cavity and gastrointestinal tract. Recent advances in bacterial identification have confirmed the clinical importance of . Here, we report a case of empyema with bacteremia caused by . We successfully treated the patient with the appropriate antibiotics and drainage. can cause respiratory infections, including empyema, which can progress to bacteremia if treatment is delayed. In infections, not only the oral cavity but also the entire body must be investigated to clarify the entry mechanism.
PubMed: 37577121
DOI: 10.1016/j.rmcr.2023.101892 -
Frontiers in Public Health 2023(), a Gram-positive anaerobic bacterium, exhibits colonization tendencies on oral mucosal and skin surfaces, potentially evolving into a pathogenic entity associated... (Review)
Review
BACKGROUND
(), a Gram-positive anaerobic bacterium, exhibits colonization tendencies on oral mucosal and skin surfaces, potentially evolving into a pathogenic entity associated with diverse diseases. The diagnostic trajectory for -related diseases encounters delays, often with severe consequences, including fatality, attributed to the absence of symptom specificity and challenges in culture. The absence of a consensus on the diagnostic and therapeutic approaches to exacerbates the complexity of addressing associated conditions. This study aims to elucidate and scrutinize the clinical manifestations linked to , drawing insights from an extensive literature review of pertinent case reports.
CASE PRESENTATION
A 53-year-old male sought medical attention at our institution presenting with recurrent hemoptysis. Empirical treatment was initiated while awaiting pathogen culture results; however, the patient's symptoms persisted. Subsequent metagenomic next-generation sequencing (mNGS) analysis revealed a pulmonary infection attributable to . Resolution of symptoms occurred following treatment with piperacillin sulbactam sodium and moxifloxacin hydrochloride. A comprehensive literature review, utilizing the PubMed database, was conducted to assess case reports over the last decade where was identified as the causative agent.
CONCLUSION
The literature analysis underscores the predilection of for immunocompromised populations afflicted by cardiovascular diseases, diabetes, orthopedic conditions, and tumors. Risk factors, including oral and periodontal hygiene, smoking, and alcohol consumption, were found to be associated with infections. Clinical manifestations encompassed fever, cough, sputum production, and back pain, potentially leading to severe outcomes such as Spondylodiscitis, septic arthritis, lung abscess, bacteremia, sepsis, and mortality. While conventional bacterial culture remains the primary diagnostic tool, emerging technologies like mNGS offer alternative considerations. In terms of treatment modalities, β-lactam antibiotics and nitroimidazoles predominated, exhibiting recovery rates of 56.10% (46/82) and 23.17% (19/82), respectively. This case report and literature review collectively aim to enhance awareness among clinicians and laboratory medicine professionals regarding the intricacies of -associated infections.
Topics: Humans; Male; Middle Aged; Base Composition; Firmicutes; Hemoptysis; Phylogeny; Piperacillin; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Gram-Positive Bacterial Infections
PubMed: 38389952
DOI: 10.3389/fpubh.2023.1307902 -
Microorganisms Aug 2023Globally, colorectal cancer (CRC) is the second most common cause of mortality worldwide. Considerable evidence indicates that dysbiosis of the gut microbial community... (Review)
Review
Globally, colorectal cancer (CRC) is the second most common cause of mortality worldwide. Considerable evidence indicates that dysbiosis of the gut microbial community and its metabolite secretions play a fundamental role in advanced adenoma (ADA) and CRC development and progression. This study is a systematic review that aims to assess the clinical association between gut microbial markers and/or gut and circulating metabolites with ADA and CRC. Five electronic databases were searched by four independent reviewers. Only controlled trials that compared ADA and/or CRC with healthy control (HC) using either untargeted (16s rRNA gene or whole genome sequencing) or targeted (gene-based real-time PCR) identification methods for gut microbiome profile, or untargeted or targeted metabolite profiling approaches from the gut or serum/plasma, were eligible. Three independent reviewers evaluated the quality of the studies using the . Twenty-four studies were eligible. We identified strong evidence of two microbial markers and for ADA vs. CRC, and nine microbial markers -Lachnoclostridium, -Ruminococcus, spp., , Enterobacteriaceae, spp., Bacteroides, -, spp.-, , and for CRC vs. HC. The remaining metabolite marker evidence between the various groups, including ADA vs. HC, ADA vs. HC, and CRC vs. HC, was not of sufficient quality to support additional findings. The identified gut microbial markers can be used in a panel for diagnosing ADA and/or CRC. Further research in the metabolite markers area is needed to evaluate the possibility to use in diagnostic or prognostic markers for colorectal cancer.
PubMed: 37630597
DOI: 10.3390/microorganisms11082037 -
Molecular Oncology May 2024Oral and intestinal samples from a cohort of 93 colorectal cancer (CRC) patients and 30 healthy controls (non-CRC) were collected for microbiome analysis. Saliva (28...
Oral and intestinal samples from a cohort of 93 colorectal cancer (CRC) patients and 30 healthy controls (non-CRC) were collected for microbiome analysis. Saliva (28 non-CRC and 94 CRC), feces (30 non-CRC and 97 CRC), subgingival fluid (20 CRC), and tumor tissue samples (20 CRC) were used for 16S metabarcoding and/or RNA sequencing (RNAseq) approaches. A differential analysis of the abundance, performed with the ANCOM-BC package, adjusting the P-values by the Holm-Bonferroni method, revealed that Parvimonas was significantly over-represented in feces from CRC patients (P-value < 0.001) compared to healthy controls. A total of 11 Parvimonas micra isolates were obtained from the oral cavity and adenocarcinoma of CRC patients. Genome analysis identified a pair of isolates from the same patient that shared 99.2% identity, demonstrating that P. micra can translocate from the subgingival cavity to the gut. The data suggest that P. micra could migrate in a synergistic consortium with other periodontal bacteria. Metatranscriptomics confirmed that oral bacteria were more active in tumor than in non-neoplastic tissues. We suggest that P. micra could be considered as a CRC biomarker detected in non-invasive samples such as feces.
Topics: Humans; Colorectal Neoplasms; Male; Female; Adenocarcinoma; Middle Aged; Aged; Mouth; Feces; RNA, Ribosomal, 16S; Gingiva; Saliva; Peptostreptococcus; Firmicutes
PubMed: 37558206
DOI: 10.1002/1878-0261.13506 -
Journal of Endodontics Jul 2023This scoping review aimed to map the evidence about the microbiota found in persistent endodontic infections. (Review)
Review
INTRODUCTION
This scoping review aimed to map the evidence about the microbiota found in persistent endodontic infections.
METHODS
The study protocol was prospectively registered and is available at https://osf.io/3g2cp. The electronic search was performed in MEDLINE via PubMed, Lilacs, BBO, Scopus, Web of Science, Cochrane Library, and Embase. The eligibility criteria were based on the PCC acronym, where P (Population) represents patients with teeth presenting persistent endodontic infection, C (Concept) represents microbial profile, and C (Context) represents undergoing endodontic retreatment. Clinical studies that evaluated the microbial profile of samples collected from root canals of teeth undergoing retreatment, using classical or molecular methods, were included. Studies that did not show a minimum period of 1 year between primary endodontic treatment and retreatment or did not radiographically evaluate the quality of primary root canal filling were excluded. Two reviewers independently selected the articles and collected data.
RESULTS
From a total of 957 articles, 161 were read in full, and 32 studies were included. The most prevalent species were Enterococcus faecalis, Parvimonas micra, Porphyromonas endodontalis, Porphyromonas gingivalis, Prevotella intermedia, Dialister invisus, Propionibacterium acnes, Tannerella forsythia, and Treponema denticola. Cases with symptomatology or inadequate root canal filling presented an increase in specific bacterial species compared to those with no symptomatology or adequate filling. A greater number of microorganisms was observed in teeth with inadequate coronal restoration compared to those with adequate restoration.
CONCLUSIONS
Persistent endodontic infections have a polymicrobial profile identified by the commonly used methods for bacterial detection/identification and are subject to the limitations present in each of those methods.
Topics: Humans; Dental Pulp Cavity; Porphyromonas gingivalis; Prevotella intermedia; Porphyromonas endodontalis
PubMed: 37211309
DOI: 10.1016/j.joen.2023.05.010 -
Journal of Endodontics May 2024In this study, we used metatranscriptomics for the first time to investigate microbial composition, functional signatures, and antimicrobial resistance gene expression...
INTRODUCTION
In this study, we used metatranscriptomics for the first time to investigate microbial composition, functional signatures, and antimicrobial resistance gene expression in endodontic infections.
METHODS
Root canal samples were collected from ten teeth, including five primary and five persistent/secondary endodontic infections. RNA from endodontic samples was extracted, and RNA sequencing was performed on a NovaSeq6000 system (Illumina). Taxonomic analysis was performed using the Kraken2 bacterial database. Then, sequences with a taxonomic classification were annotated against the Universal Protein Knowledgebase for functional annotation and the Comprehensive Antibiotic Resistance Database for AR-like gene identification.
RESULTS
Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria represented the dominant phyla, whereas Fusobacteria, Spirochetes, and Synergistetes were among the nondominant phyla. The top ten species were mainly represented by obligate (or quasiobligate) anaerobes, including Gram-negative (eg, Capnocytophaga sp. oral taxon 323, Fusobacterium nucleatum, Prevotella intermedia, Prevotella oris, Tannerella forsythia, and Tannerella sp. oral taxon HOT-286) and Gram-positive species (eg, Olsenella uli and Parvimonas micra). Transcripts encoding moonlighting proteins (eg, glycolytic proteins, translational elongation factors, chaperonin, and heat shock proteins) were highly expressed, potentially affecting bacterial adhesion, biofilm formation, host defense evasion, and inflammation induction. Endodontic bacteria expressed genes conferring resistance to antibiotic classes commonly used in dentistry, with a high prevalence and expression of tetracycline and lincosamide resistance genes. Antibiotic efflux and antibiotic target alteration/protection were the main resistance mechanisms.
CONCLUSIONS
Metatranscriptomics revealed the activity of potential endodontic pathogens, which expressed putative virulence factors and a wide diversity of genes potentially involved in AR.
PubMed: 38719087
DOI: 10.1016/j.joen.2024.03.015