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Microbial Genomics Mar 2024The aetiological mechanisms of in laryngeal cancer remain unclear. This study aimed to reveal the epigenetic signature induced by in laryngeal squamous cell carcinoma...
The aetiological mechanisms of in laryngeal cancer remain unclear. This study aimed to reveal the epigenetic signature induced by in laryngeal squamous cell carcinoma (LSCC). Combined analysis of methylome and transcriptome data was performed to address the functional role of in laryngeal cancer. Twenty-nine differentially expressed methylation-driven genes were identified by mapping the methylation levels of significant differential methylation sites to the expression levels of related genes. The combined analysis revealed that promoted Janus kinase 3 (JAK3) gene expression in LSCC. Further validation found decreased methylation and elevated expression of JAK3 in the treated LSCC cell group; abundance and JAK3 gene expression had a positive correlation in tumour tissues. This analysis provides a novel understanding of the impact of in the methylome and transcriptome of laryngeal cancer. Identification of these epigenetic regulatory mechanisms opens up new avenues for mechanistic studies to explore novel therapeutic strategies.
Topics: Humans; Epigenome; Fusobacterium nucleatum; Laryngeal Neoplasms; Epigenesis, Genetic; Gene Expression Profiling
PubMed: 38536233
DOI: 10.1099/mgen.0.001221 -
Gut Microbes 2024Chemotherapy resistance is one of the main reasons for the poor prognosis of colorectal cancer (CRC). Moreover, dysbiosis of gut bacteria was found to be a specific...
Chemotherapy resistance is one of the main reasons for the poor prognosis of colorectal cancer (CRC). Moreover, dysbiosis of gut bacteria was found to be a specific environmental risk factor. In this study, enrichment of was elucidated to be significantly associated with CRC recurrence after chemotherapy. Functional experiments showed that could inhibit pyroptosis induced by chemotherapy drugs, thereby inducing chemoresistance. Furthermore, mechanistic investigation demonstrated that could regulate the Hippo pathway and promote the expression of BCL2, thereby inhibiting the Caspase-3/GSDME pyroptosis-related pathway induced by chemotherapy drugs and mediating CRC cell chemoresistance. Taken together, these results validated the significant roles of in CRC chemoresistance, which provided an innovative theoretical basis for the clinical diagnosis and therapy of CRC.
Topics: Humans; Fusobacterium nucleatum; Colorectal Neoplasms; Hippo Signaling Pathway; Drug Resistance, Neoplasm; Pyroptosis; Gastrointestinal Microbiome; Neoplasm Recurrence, Local
PubMed: 38533566
DOI: 10.1080/19490976.2024.2333790 -
Microbial Genomics Mar 2024is an anaerobic commensal of the oral cavity associated with periodontitis and extra-oral diseases, including colorectal cancer. Previous studies have shown an...
subsp. recovered from malignant and potentially malignant oral disease exhibit heterogeneity in adhesion phenotypes and adhesin gene copy number, shaped by inter-subspecies horizontal gene transfer and recombination-derived mosaicism.
is an anaerobic commensal of the oral cavity associated with periodontitis and extra-oral diseases, including colorectal cancer. Previous studies have shown an increased relative abundance of this bacterium associated with oral dysplasia or within oral tumours. Using direct culture, we found that 75 % of species isolated from malignant or potentially malignant oral mucosa were subsp. . Whole genome sequencing and pangenome analysis with Panaroo was carried out on 76 . subsp. genomes. subsp. was shown to possesses a relatively small core genome of 1604 genes in a pangenome of 7363 genes. Phylogenetic analysis based on the core genome shows the isolates can be separated into three main clades with no obvious genotypic associations with disease. Isolates recovered from healthy and diseased sites in the same patient are generally highly related. A large repertoire of adhesins belonging to the type V secretion system (TVSS) could be identified with major variation in repertoire and copy number between strains. Analysis of intergenic recombination using fastGEAR showed that adhesin complement is shaped by horizontal gene transfer and recombination. Recombination events at TVSS adhesin genes were not only common between lineages of subspecies but also between different subspecies of . Strains of subspecies with low copy numbers of TVSS adhesin encoding genes tended to have the weakest adhesion to oral keratinocytes. This study highlights the genetic heterogeneity of subsp. and provides a new framework for defining virulence in this organism.
Topics: Humans; Mosaicism; Phylogeny; Gene Transfer, Horizontal; Fusobacterium; Phenotype; Gene Dosage
PubMed: 38529905
DOI: 10.1099/mgen.0.001217 -
Nature Apr 2024Fusobacterium nucleatum (Fn), a bacterium present in the human oral cavity and rarely found in the lower gastrointestinal tract of healthy individuals, is enriched in...
Fusobacterium nucleatum (Fn), a bacterium present in the human oral cavity and rarely found in the lower gastrointestinal tract of healthy individuals, is enriched in human colorectal cancer (CRC) tumours. High intratumoural Fn loads are associated with recurrence, metastases and poorer patient prognosis. Here, to delineate Fn genetic factors facilitating tumour colonization, we generated closed genomes for 135 Fn strains; 80 oral strains from individuals without cancer and 55 unique cancer strains cultured from tumours from 51 patients with CRC. Pangenomic analyses identified 483 CRC-enriched genetic factors. Tumour-isolated strains predominantly belong to Fn subspecies animalis (Fna). However, genomic analyses reveal that Fna, considered a single subspecies, is instead composed of two distinct clades (Fna C1 and Fna C2). Of these, only Fna C2 dominates the CRC tumour niche. Inter-Fna analyses identified 195 Fna C2-associated genetic factors consistent with increased metabolic potential and colonization of the gastrointestinal tract. In support of this, Fna C2-treated mice had an increased number of intestinal adenomas and altered metabolites. Microbiome analysis of human tumour tissue from 116 patients with CRC demonstrated Fna C2 enrichment. Comparison of 62 paired specimens showed that only Fna C2 is tumour enriched compared to normal adjacent tissue. This was further supported by metagenomic analysis of stool samples from 627 patients with CRC and 619 healthy individuals. Collectively, our results identify the Fna clade bifurcation, show that specifically Fna C2 drives the reported Fn enrichment in human CRC and reveal the genetic underpinnings of pathoadaptation of Fna C2 to the CRC niche.
Topics: Animals; Humans; Mice; Adenoma; Case-Control Studies; Colorectal Neoplasms; Feces; Fusobacterium nucleatum; Gastrointestinal Tract; Genome, Bacterial; Mouth; Female
PubMed: 38509359
DOI: 10.1038/s41586-024-07182-w -
Scientific Reports Mar 2024The oral and gastrointestinal mucosae represent the main targets of the toxic effect of chemo and/or radiotherapy administered during the conditioning regimen before...
The oral and gastrointestinal mucosae represent the main targets of the toxic effect of chemo and/or radiotherapy administered during the conditioning regimen before hematopoietic stem cell transplant (HSCT). These harmful consequences and the immunological complications that may occur after the transplant (such as Graft versus Host Disease, GvHD) are responsible for the clinical symptoms associated with mucositis during the aplasia phase, like pain, nausea, vomiting, and diarrhea. These toxicities could play a critical role in the oral and gastrointestinal microbiomes during the post-transplant phase, and the degree of microbial dysbiosis and dysregulation among different bacterial species could also be crucial in intestinal mucosa homeostasis, altering the host's innate and adaptive immune responses and favoring abnormal immune responses responsible for the occurrence of GvHD. This prospective pediatric study aims to analyze longitudinally oral and gut microbiomes in 17 pediatric patients who received allogeneic HSCT for malignant and non-malignant diseases. The oral mucositis was mainly associated with an increased relative abundance of Fusobacteria, and Prevotella species, while Streptococcus descendants showed a negative correlation. The fecal microbiome of subjects affected by cutaneous acute GvHD (aGvHD) correlated with Proteobacteria. Oral mucosal microbiota undergoes changes after HSCT, Fusobacteria, and Prevotella represent bacterial species associated with mucositis and they could be the target for future therapeutic approaches, while fecal microbiome in patients with acute GvHD (aGvHD) revealed an increase of different class of Proteobacteria (Alphaproteobacteria and Deltaproteobacteria) and a negative correlation with the class of Gammaproteobacteria.
Topics: Humans; Child; Mucositis; Dysbiosis; Prospective Studies; Microbiota; Graft vs Host Disease; Bacteria; Hematopoietic Stem Cell Transplantation
PubMed: 38509104
DOI: 10.1038/s41598-024-55690-6 -
Cureus Feb 2024Introduction Graphene oxide (GO) has emerged as a promising material in dentistry, leveraging its exceptional properties. This study evaluates the physicochemical...
Introduction Graphene oxide (GO) has emerged as a promising material in dentistry, leveraging its exceptional properties. This study evaluates the physicochemical attributes of GO and elucidates its derived biological properties. These encompass biocompatibility, antibacterial efficacy, as well as its influence on osteogenic and odontogenic differentiation processes. Understanding the intricate interplay between the physicochemical and biological aspects of GO provides valuable insights into its potential applications in various dental contexts. Materials and methods The study group (so; titanium discs surface coated with GO) and the control group (co; plain/uncoated machined titanium discs) were divided based on cell attachment and cell proliferation assays (n=60). These groups were further divided into subgroups (n=30) based on the tested time intervals, specifically 24 hours, 48 hours, and 72 hours. The study and controlgroups were further subdivided into three subgroups (n=10) based on the microorganisms tested i.e and Results The results of this in vitro study suggest that GO-coated titanium dental implants have both increased osteogenic potential and antimicrobial efficacy. Graphene has good potential as a promising alternative to traditional surface treatments, and a graphene-coated implant can be used for enhanced osseointegration. Conclusion The osteogenic potential and the cell attachment were higher on titanium surfaces coated with GO nanoparticles when compared to plain titanium discs at 24, 48 and 72 hours respectively.
PubMed: 38496143
DOI: 10.7759/cureus.54172 -
Brazilian Oral Research 2024The present study aimed to evaluate the influence of titanium surface nanotopography on the initial bacterial adhesion process by in vivo and in vitro study models....
The present study aimed to evaluate the influence of titanium surface nanotopography on the initial bacterial adhesion process by in vivo and in vitro study models. Titanium disks were produced and characterized according to their surface topography: machined (Ti-M), microtopography (Ti-Micro), and nanotopography (Ti-Nano). For the in vivo study, 18 subjects wore oral acrylic splints containing 2 disks from each group for 24 h (n = 36). After this period, the disks were removed from the splints and evaluated by microbial culture method, scanning electron microscopy (SEM), and qPCR for quantification of Streptococcus oralis, Actinomyces naeslundii, Fusobacterium nucleatum, as well as total bacteria. For the in vitro study, adhesion tests were performed with the species S. oralis and A. naeslundii for 24 h. Data were compared by ANOVA, with Tukey's post-test. Regarding the in vivo study, both the total aerobic and total anaerobic bacteria counts were similar among groups (p > 0.05). In qPCR, there was no difference among groups of bacteria adhered to the disks (p > 0.05), except for A. naeslundii, which was found in lower proportions in the Ti-Nano group (p < 0.05). In the SEM analysis, the groups had a similar bacterial distribution, with a predominance of cocci and few bacilli. In the in vitro study, there was no difference in the adhesion profile for S. oralis and A. naeslundii after 24 h of biofilm formation (p > 0.05). Thus, we conclude that micro- and nanotopography do not affect bacterial adhesion, considering an initial period of biofilm formation.
Topics: Humans; Bacterial Adhesion; Titanium; Fusobacterium nucleatum; Microscopy, Electron, Scanning; Research Design
PubMed: 38477807
DOI: 10.1590/1807-3107bor-2024.vol38.0021 -
Animals : An Open Access Journal From... Feb 2024Dietary protein quality plays a key role in maintaining intestinal mucosal integrity, but also modulates the growth of luminal microorganisms. This work assessed the...
Dietary protein quality plays a key role in maintaining intestinal mucosal integrity, but also modulates the growth of luminal microorganisms. This work assessed the effect of dietary protein sources on the performance, gut morphology, and microbiome in Nile tilapia. Four isonitrogenous and isolipidic diets comprising equivalent amounts of the protein supply derived from either PLANT, ANIMAL, INSECT, or BACTERIAL (bacterial biomass) sources were fed to triplicate groups of fish (IBW: 12 g) for 46 days. Fish fed the ANIMAL and BACTERIAL diets showed significantly higher weight gains than those fed the PLANT and INSECT diets ( < 0.05). Relative abundance at the phylum level showed that Bacteroidetes, Fusobacteria, and Proteobacteria were the more abundant phyla in tilapia's intestine, while was the most representative genus in all treatments. Interesting patterns were observed in the correlation between amino acid intake and genus and species abundance. Metabolism prediction analysis showed that BACTERIAL amine and polyamine degradation pathways are modulated depending on diets. In conclusion, different protein sources modulate the relationship between bacteria functional pathways and amino acid intake.
PubMed: 38473099
DOI: 10.3390/ani14050714 -
Gut Pathogens Mar 2024The gut microbiota is associated with risk for colorectal cancer (CRC), a chronic disease for which racial disparities persist with Black Americans having a higher risk...
BACKGROUND
The gut microbiota is associated with risk for colorectal cancer (CRC), a chronic disease for which racial disparities persist with Black Americans having a higher risk of CRC incidence and mortality compared to other groups. Given documented racial differences, the gut microbiota may offer some insight into previously unexplained racial disparities in CRC incidence and mortality. A case-control analysis comparing 11 women newly diagnosed with CRC with 22 cancer-free women matched on age, BMI, and race in a 1:2 ratio was conducted. Information about participants' diet and perceived stress levels were obtained via 24-h Dietary Recall and Perceived Stress Scale-10 survey, respectively. Participants provided stool samples from which microbial genomic DNA was extracted to reveal the abundance of 26 genera chosen a priori based on their previously observed relevance to CRC, anxiety symptoms, and diet.
RESULTS
Significantly lower alpha diversity was observed among cancer-free Black women compared to all other race-cancer status combinations. No group differences were observed when comparing beta diversity. Non-Hispanic White CRC cases tended to have higher relative abundance of Fusobacteria, Gemellaceae, and Peptostreptococcus compared to all other race-cancer combination groups. Perceived stress was inversely associated with alpha diversity and was associated with additional genera.
CONCLUSIONS
Our findings suggest that microbiome-CRC associations may differ by racial group. Additional large, racially diverse population-based studies are needed to determine if previously identified associations between characteristics of the gut microbiome and CRC are generalizable to Black women and other racial, ethnic, and gender groups.
PubMed: 38468325
DOI: 10.1186/s13099-024-00608-w -
Frontiers in Immunology 2024There exists a bidirectional relationship between oral health and general well-being, with an imbalance in oral symbiotic flora posing a threat to overall human health.... (Review)
Review
There exists a bidirectional relationship between oral health and general well-being, with an imbalance in oral symbiotic flora posing a threat to overall human health. Disruptions in the commensal flora can lead to oral diseases, while systemic illnesses can also impact the oral cavity, resulting in the development of oral diseases and disorders. and , known as pathogenic bacteria associated with periodontitis, play a crucial role in linking periodontitis to accompanying systemic diseases. In periodontal tissues, these bacteria, along with their virulence factors, can excessively activate the host immune system through local diffusion, lymphatic circulation, and blood transmission. This immune response disruption contributes to an imbalance in osteoimmune mechanisms, alveolar bone resorption, and potential systemic inflammation. To restore local homeostasis, a deeper understanding of microbiota-host interactions and the immune network phenotype in local tissues is imperative. Defining the immune network phenotype in periodontal tissues offers a promising avenue for investigating the complex characteristics of oral plaque biofilms and exploring the potential relationship between periodontitis and associated systemic diseases. This review aims to provide an overview of the mechanisms underlying - and -induced alveolar bone resorption, as well as the immunophenotypes observed in host periodontal tissues during pathological conditions.
Topics: Humans; Periodontitis; Alveolar Bone Loss; Porphyromonas gingivalis; Inflammation; Fusobacterium nucleatum
PubMed: 38455060
DOI: 10.3389/fimmu.2024.1254516