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Molecular Oncology May 2024The incidence of colorectal cancer (CRC) has increased worldwide, and early diagnosis is crucial to reduce mortality rates. Therefore, new noninvasive biomarkers for CRC...
The incidence of colorectal cancer (CRC) has increased worldwide, and early diagnosis is crucial to reduce mortality rates. Therefore, new noninvasive biomarkers for CRC are required. Recent studies have revealed an imbalance in the oral and gut microbiomes of patients with CRC, as well as impaired gut vascular barrier function. In the present study, the microbiomes of saliva, crevicular fluid, feces, and non-neoplastic and tumor intestinal tissue samples of 93 CRC patients and 30 healthy individuals without digestive disorders (non-CRC) were analyzed by 16S rRNA metabarcoding procedures. The data revealed that Parvimonas, Fusobacterium, and Bacteroides fragilis were significantly over-represented in stool samples of CRC patients, whereas Faecalibacterium and Blautia were significantly over-abundant in the non-CRC group. Moreover, the tumor samples were enriched in well-known periodontal anaerobes, including Fusobacterium, Parvimonas, Peptostreptococcus, Porphyromonas, and Prevotella. Co-occurrence patterns of these oral microorganisms were observed in the subgingival pocket and in the tumor tissues of CRC patients, where they also correlated with other gut microbes, such as Hungatella. This study provides new evidence that oral pathobionts, normally located in subgingival pockets, can migrate to the colon and probably aggregate with aerobic bacteria, forming synergistic consortia. Furthermore, we suggest that the group composed of Fusobacterium, Parvimonas, Bacteroides, and Faecalibacterium could be used to design an excellent noninvasive fecal test for the early diagnosis of CRC. The combination of these four genera would significantly improve the reliability of a discriminatory test with respect to others that use a single species as a unique CRC biomarker.
Topics: Humans; Colorectal Neoplasms; Fusobacterium; Male; Female; Bacteroides; Middle Aged; Feces; Biomarkers, Tumor; Faecalibacterium; Aged; RNA, Ribosomal, 16S; Gastrointestinal Microbiome; Saliva; Adult
PubMed: 38366793
DOI: 10.1002/1878-0261.13604 -
International Endodontic Journal Jul 2024The aim of this study was to analyse and compare the microbiome present in root canals and periapical lesions of teeth with post-treatment infections, and to identify...
AIM
The aim of this study was to analyse and compare the microbiome present in root canals and periapical lesions of teeth with post-treatment infections, and to identify the presence of keystone taxa in both habitats using next-generation sequencing analysis.
METHODOLOGY
Apices and periapical lesions of patients with post-treatment apical periodontitis were surgically extracted. Specimens were cryo-pulverized, bacterial DNA was extracted, and the V3-V4 hypervariable regions of the 16S rRNA gene were sequenced using the Illumina Miseq platform. Bioinformatic analysis was carried out with Mothur software, whilst diversity indices were obtained using operational taxonomic units (OTUs). The diversity indices were compared with the Kruskal-Wallis test, and community composition differences were explored with Permutational Multivariate Analysis of Variance (PERMANOVA). A bacterial functional study was performed with the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis. Co-occurrence network analyses were performed using the Sparse Correlations for Compositional data (SparCC). Eigencentrality, clr-based abundance and ubiquitousness were applied to infer keystone taxa. P values <.05 were considered statistically significant.
RESULTS
Thirty-two apices and thirty-nine periapical lesions were sequenced and analysed. A similar alpha-diversity (p < .05) and community composition (p = .91) was observed for apices and lesion samples. The most abundant OTUs identified amongst all samples included Fusobacterium nucleatum, Prevotella loescheii, Streptococcus intermedius, Porphyromonas gingivalis, Parvimonas micra, Synergistetes bacterium, Tannerella forsythia and Peptostreptococcus stomatis. The metabolic pathways with >0.81% abundances included membrane transport, genetic information processing and metabolic pathways. F. nucleatum was identified as a keystone taxon as it showed ubiquitousness, an eigenvector centrality value of 0.83 and a clr-based abundance >4.
CONCLUSIONS
The microbiome in apices and periapical lesions of post-treatment endodontic infections showed a similar diversity and taxonomic composition. Co-occurrence network analyses at OTU level identified F. nucleatum as a keystone taxon candidate in these infections.
Topics: Humans; Dental Pulp Cavity; Periapical Periodontitis; Microbiota; RNA, Ribosomal, 16S; Adult; Middle Aged; Male; DNA, Bacterial; Female; High-Throughput Nucleotide Sequencing; Phylogeny; Root Canal Therapy; Bacteria
PubMed: 38357799
DOI: 10.1111/iej.14046 -
American Journal of Translational... 2024The prevalence of allergic rhinitis (common allergies) has increased in the last fifty years, from less than one percent to more than twenty-six percent of the...
The prevalence of allergic rhinitis (common allergies) has increased in the last fifty years, from less than one percent to more than twenty-six percent of the population. Today, more than one hundred million people in the US suffer seasonal or yearlong allergies. The hygiene hypothesis was proposed 30 years ago as a potential explanation for this phenomenon, and we built on it with the specific oral hygiene hypothesis. Our longitudinal pilot study suggested that oral probiotic deficiency is the cause of allergic rhinitis. This clinical trial served to verify our theory and evaluate the effectiveness of AllerPops for allergy relief. We carried out a phase II, randomized, double-blind, controlled, single-center 21-day study to investigate the efficacy of AllerPops to reduce nasal symptoms in 72 adult volunteers with seasonal/year-long nasal allergies and its impact on oral microbiome using amplicon sequencing of 16S ribosome RNA genes. The volunteers were randomly separated into two equally sized groups: a control group and an investigational group. Both groups were given at least three doses of AllerPops, taken every other day, and asked to answer questions about observed allergy symptoms. Volunteers in the investigational group cleaned their mouths before taking a dose and slowly dissolve the lozenge, while those in the control did not. Through this trial, we show that AllerPops prebiotic supplements are effective in providing sustained allergy relief (P = 0.002) and can modulate oral beneficial bacteria that produce short-chain fatty acids (SCFA), such as Fusobacteria, Butyrivibrio, and Peptostreptococcus. The clinical improvements correlated with changes in the relative abundance of probiotics significantly: Fusobacteria (R = 0.32, P = 0.009), Butyrivibrio (R = 0.25, P = 0.044), and Peptostreptococcus (R = 0.34, P = 0.005). These results point to the root cause of allergic rhinitis: the lack of oral probiotics that produce SCFA to pacify the immune systems. Future study of AllerPops' theory will help society redefine the best oral hygiene practice to protect oral probiotics so that we may prevent allergic and autoimmune diseases and dental/gum infections. The trial was retrospectively registered at clinicaltrials.com, with registration number NCT05956691, on 21/07/2023.
PubMed: 38322553
DOI: 10.62347/JWOU4205 -
International Journal of Systematic and... Feb 2024The family , which contains 15 genera including , presently lacks proper circumscription. Using 52 available genomes for species, we report comprehensive phylogenomic...
The family , which contains 15 genera including , presently lacks proper circumscription. Using 52 available genomes for species, we report comprehensive phylogenomic and comparative analyses to reliably discern their evolutionary relationships. In phylogenetic trees based on core genome proteins and 16S rRNA gene sequences, the examined species formed a strongly supported clade designated as . This clade encompassed the genera (type genus), , , , , , , and , and two misclassified species (. and ''). The distinctness of this clade is strongly supported by eight identified conserved signature indels (CSIs), which are specific for the species from this clade. Based on the robust evidence provided by presented studies, we are proposing the emendment of family to only the genera within the clade. We also report 67 other novel CSIs, which reliably demarcate different species clades and clarify the classification of some misclassified species. Based on the consistent evidence obtained from different presented studies, we are making the following proposals to clarify the classification of species: (i) transfer of , and as comb. nov. into the genus ; (ii) transfer of as a comb. nov. into gen. nov.; (iii) classification of ' as a novel species gen. nov., sp. nov. (type strain FF1; genome and 16S rRNA accession numbers GCA_000499525.1 and KC517358, respectively); (iv) transfer of two misclassified species, and , into gen. nov.; and (v) proposals for two novel families, fam. nov. and fam. nov., to accommodate remaining unclassified genera. The described CSIs specific for different families and genera provide novel and reliable means for the identification, diagnostics and biochemical studies on these bacteria.
Topics: Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA; DNA, Bacterial; Bacterial Typing Techniques; Base Composition; Fatty Acids; Clostridiaceae; Eubacterium; Clostridiales
PubMed: 38319314
DOI: 10.1099/ijsem.0.006247 -
Frontiers in Oncology 2023Colon microbiome composition contributes to the pathogenesis of colorectal cancer (CRC) and prognosis. We analyzed 16S rRNA sequencing data from tumor samples of...
BACKGROUND
Colon microbiome composition contributes to the pathogenesis of colorectal cancer (CRC) and prognosis. We analyzed 16S rRNA sequencing data from tumor samples of patients with metastatic CRC and determined the clinical implications.
MATERIALS AND METHODS
We enrolled 133 patients with metastatic CRC at St. Vincent Hospital in Korea. The V3-V4 regions of the 16S rRNA gene from the tumor DNA were amplified, sequenced on an Illumina MiSeq, and analyzed using the DADA2 package.
RESULTS
After excluding samples that retained <5% of the total reads after merging, 120 samples were analyzed. The median age of patients was 63 years (range, 34-82 years), and 76 patients (63.3%) were male. The primary cancer sites were the right colon (27.5%), left colon (30.8%), and rectum (41.7%). All subjects received 5-fluouracil-based systemic chemotherapy. After removing genera with <1% of the total reads in each patient, 523 genera were identified. Rectal origin, high CEA level (≥10 ng/mL), and presence of lung metastasis showed higher richness. Survival analysis revealed that the presence of ( = 0.052), ( = 0.002), (<0.001), ( = 0.001), ( = 0.007), ( = 0.002), and ( = 0.003) were associated with short overall survival (OS, <24 months), while the presence of was associated with long OS ( = 0.070). From the multivariate analysis, the presence of (hazard ratio [HR], 6.35; 95% confidence interval [CI], 2.38-16.97; <0.001) was associated with poor prognosis along with high CEA level.
CONCLUSION
Tumor microbiome features may be useful prognostic biomarkers for metastatic CRC.
PubMed: 38304032
DOI: 10.3389/fonc.2023.1310054 -
Cellular Signalling Apr 2024Colorectal cancer (CRC) is the third most common cancer in the world with high mortality rate. EHLJ7 is a quaternary coptisine derivative synthesized by our institute....
Colorectal cancer (CRC) is the third most common cancer in the world with high mortality rate. EHLJ7 is a quaternary coptisine derivative synthesized by our institute. In this study, the role and mechanism of EHLJ7 on CRC are further elucidated. Using target fishing, colon cancer-associated target screening and molecular docking analysis, PI3K/AKT pathway was selected for the target of EHLJ7 at CRC. Results of Flow cytometry, wound healing assay and transwell migration assay confirmed that EHLJ7 could inhibit migration and apoptosis of colon cancer cells by specifically inhibiting PI3K/AKT pathway in vitro. Xenograft tumor models and a newly established azoxymethane (AOM)/dextran sulfate sodium (DSS)/Peptostreptococcus anaerobiu (P.anaerobius)-induced CRC mouse model are applied to access the anti-cancer action and mechanism of EHLJ7 using western-blot, immunohistochemistry and analysis of exosomes. The key findings in this study are listed as follows: (1) EHLJ7 exerts superior anti-tumor effect with good safety on Xenograft tumor model and CRC model; (2) EHLJ7 exerted its anti-CRC effect by specifically inhibiting PI3K/AKT pathway and apoptosis in vivo and in vitro. In summary, we demonstrated that EHLJ7 exerts therapeutic effect against CRC by PI3K/AKT pathway, which made it possible as a potentially effective compound for the treatment of CRC.
Topics: Animals; Mice; Humans; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Signal Transduction; Molecular Docking Simulation; Colorectal Neoplasms; Colonic Neoplasms; Berberine
PubMed: 38224723
DOI: 10.1016/j.cellsig.2024.111053 -
The Science of the Total Environment Mar 2024Waterbirds are vectors for the dissemination of antimicrobial resistance across environments, with some species increasingly reliant on highly anthropized habitats for...
Waterbirds are vectors for the dissemination of antimicrobial resistance across environments, with some species increasingly reliant on highly anthropized habitats for feeding. However, data on the impact of their feeding habits on the carriage of antibiotic resistance genes (ARGs) are still scarce. To fill this gap, we examined the microbiota (16S rRNA amplicon gene sequencing) and the prevalence of ARG (high-throughput qPCR of 47 genes) in faeces from white storks (Ciconia ciconia) and lesser black-backed gulls (Larus fuscus) feeding in highly (landfill) and less (paddy fields) polluted habitats. Faecal bacterial richness and diversity were higher in gulls feeding upon landfills and showed a greater abundance of potential pathogens, such as Staphylococcus. In contrast, faecal bacterial communities from storks were similar regardless of habitat preferences, maybe due to a less intense habitat use compared to gulls. In addition, birds feeding in the landfill carried a higher burden of ARGs compared to the surrounding soil and surface waters. Network analysis revealed strong correlations between ARGs and potential pathogens, particularly between tetM (resistance to tetracyclines), bla (beta-lactam resistance), sul1 (sulfonamide resistance) and members of the genera Streptococcus, Peptostreptococcus, and Peptoclostridium. Our work demonstrates how transitioning from paddy fields to landfills fosters the carriage of ARGs and potential pathogens in the bird gut, shedding light on the ecological role of these avian vectors in antimicrobial resistance dissemination.
Topics: Animals; Charadriiformes; RNA, Ribosomal, 16S; Birds; Anti-Bacterial Agents; Drug Resistance, Microbial; Bacteria; Genes, Bacterial; Microbiota; Waste Disposal Facilities
PubMed: 38199372
DOI: 10.1016/j.scitotenv.2024.169946 -
BioRxiv : the Preprint Server For... Dec 2023The human oral and nasal cavities can act as reservoirs for opportunistic pathogens capable of causing acute infection. These microbes asymptomatically colonize the...
The human oral and nasal cavities can act as reservoirs for opportunistic pathogens capable of causing acute infection. These microbes asymptomatically colonize the human oral and nasal cavities which facilitates transmission within human populations via the environment, and they routinely possess a clinically-significant antibiotic-resistance genes. Among these opportunistic pathogens, the genus stands out as a notable example, with its members frequently linked to nosocomial infections and multidrug resistance. As with many colonizing opportunistic pathogens, how transitions from an asymptomatic colonizer to a pathogen remains unclear. Here, we explored a possible explanation by investigating the ability of oral and nasal to outcompete their native microbial community members under starvation conditions, which could be analogous to external hospital environments. When was present within a healthy human oral or nasal sample, the bacterial community composition shifted dramatically under starvation conditions and typically became dominated by . Furthermore, introducing exogenously into a native microbial community lacking , even at low inoculum, led to repeated dominance under starvation. strains isolated from healthy individuals' oral and nasal cavities also exhibited resistance to multiple classes of antibiotics and were genetically similar to clinical and gut isolates. In addition, we found that in the absence of , other understudied opportunistic pathogens, such as , dominate under starvation conditions. Our findings establish an environmental circumstance that allows for the outgrowth of and other opportunistic pathogens. The ability to outcompete other commensal bacteria and to persist under harsh environmental conditions may contribute to the colonization-to-infection transition of these opportunistic pathogens.
PubMed: 38187725
DOI: 10.1101/2023.12.18.572173 -
Frontiers in Oncology 2023Head and neck cancer (HNC) is the sixth most common type of cancer, with more than half a million new cases annually. This review focuses on the role of oral dysbiosis... (Review)
Review
Head and neck cancer (HNC) is the sixth most common type of cancer, with more than half a million new cases annually. This review focuses on the role of oral dysbiosis and HPV infection in HNCs, presenting the involved taxons, molecular effectors and pathways, as well as the HPV-associated particularities of genetic and epigenetic changes and of the tumor microenvironment occurred in different stages of tumor development. Oral dysbiosis is associated with the evolution of HNCs, through multiple mechanisms such as inflammation, genotoxins release, modulation of the innate and acquired immune response, carcinogens and anticarcinogens production, generation of oxidative stress, induction of mutations. Thus, novel microbiome-derived biomarkers and interventions could significantly contribute to achieving the desideratum of personalized management of oncologic patients, regarding both early diagnosis and treatment. The results reported by different studies are not always congruent regarding the variations in the abundance of different taxons in HNCs. However, there is a consistent reporting of a higher abundance of Gram-negative species such as , which are probably responsible of chronic inflammation and modulation of tumor microenvironment. is the dominant fungi found in oral carcinoma being also associated with shorter survival rate. Specific microbial signatures (e.g., and ) have been associated with later stages and larger tumor, suggesting their potential to be used as biomarkers for tumor stratification and prognosis. On the other hand, increased abundance of is associated with a reduced risk of HNC. Microbiome could also provide biomarkers for differentiating between oropharyngeal and hypopharyngeal cancers as well as between HPV-positive and HPV-negative tumors. Ongoing clinical trials aim to validate non-invasive tests for microbiome-derived biomarkers detection in oral and throat cancers, especially within high-risk populations. Oro-pharyngeal dysbiosis could also impact the HNCs therapy and associated side-effects of radiotherapy, chemotherapy, and immunotherapy. HPV-positive tumors harbor fewer mutations, as well as different DNA methylation pattern and tumor microenvironment. Therefore, elucidation of the molecular mechanisms by which oral microbiota and HPV infection influence the HNC initiation and progression, screening for HPV infection and vaccination against HPV, adopting a good oral hygiene, and preventing oral dysbiosis are important tools for advancing in the battle with this public health global challenge.
PubMed: 38179168
DOI: 10.3389/fonc.2023.1273516 -
Infectious Disorders Drug Targets 2024
Background: Infections caused by anaerobic bacteria occur frequently and can be serious and life-threatening. Anaerobes are a rare cause of community-acquired... (Review)
Review
Background: Infections caused by anaerobic bacteria occur frequently and can be serious and life-threatening. Anaerobes are a rare cause of community-acquired pneumonia with Streptococcus pneumonia and respiratory viruses being the most frequently detected pathogens. We, herein, report a case of parapneumonic effusion with empyema in a patient without risk factors for aspiration pneumonia. This case presents an opportunity to discuss an unusual case of community-acquired empyema secondary to anaerobic infection in a patient without the common risk factors for aspiration.
Case Presentation: A 59-year-old male patient without significant past medical history apart from a twenty-five-year history of smoking presented due to left flank pain and shortness of breath. Findings of a complicated parapneumonic effusion were found on imaging, resulting in surgical decortication and prolonged antibiotic therapy.
Discussion: Parapneumonic effusions and empyema are relatively common complications of pneumonia. It is important to note that the incidence of anaerobic empyema has been on the rise due to more modern culturing techniques.
Conclusion: This case highlights an unusual presentation of community-acquired empyema secondary to anaerobes without any risk factors for aspiration pneumonia. Therefore, clinicians should consider the possibility of anaerobic coverage in the treatment of community-acquired empyema in the appropriate setting.
.Topics: Humans; Male; Middle Aged; Anti-Bacterial Agents; Community-Acquired Infections; Peptostreptococcus; Fusobacterium; Empyema, Pleural; Empyema; Fusobacterium Infections; Gram-Positive Bacterial Infections
PubMed: 38178665
DOI: 10.2174/0118715265255809231107100450