-
Journal of Oral Microbiology 2022Recently, the possibility that oral microbiomes is associated with oral squamous cell carcinoma (OSCC) initiation and progression has attracted attention; however, this...
OBJECTIVE
Recently, the possibility that oral microbiomes is associated with oral squamous cell carcinoma (OSCC) initiation and progression has attracted attention; however, this association is still unclear. Here, we comprehensively analyze the microbiome profiles of saliva samples using next-generation sequencing followed by determining the association between oral microbiome profiles and OSCC.
MATERIALS AND METHODS
Microbiome profiles in saliva samples from patients with OSCC, oral leukoplakia (OLK), and postoperative OSCC (Post) were analyzed. Candidate OSCC-associated bacteria were identified by comparing the bacterial diversity and relative abundance of each group based on these microbiome profiles, and their applicability as OSCC detection tools were evaluated.
RESULTS
There were significant differences in genus abundances (, and ) among the groups from saliva samples. In the OSCC group, compared with the OLK and Post groups, abundances of the genus , phylum and phylum were markedly increased and that of the genus and phylum were decreased.
CONCLUSION
The results suggested a strong association of these bacteria with OSCC. Especially, phylum was significantly associated with early recurrence of OSCC. Thus, oral microbiome analysis may have a potential of novel OSCC detection and prognostic tool.
PubMed: 35958277
DOI: 10.1080/20002297.2022.2105574 -
Frontiers in Cellular and Infection... 2022is a common oral opportunistic bacterium that can cause different infections. In recent years, studies have shown that is enriched in lesions in periodontal diseases,... (Review)
Review
is a common oral opportunistic bacterium that can cause different infections. In recent years, studies have shown that is enriched in lesions in periodontal diseases, halitosis, dental pulp infection, oral cancer, and systemic diseases. Hence, it can promote the development and/or progression of these conditions. The current study aimed to assess research progress in the epidemiological evidence, possible pathogenic mechanisms, and treatment methods of in oral and systemic diseases. Novel viewpoints obtained in recent studies can provide knowledge about the role of in hosts and a basis for identifying new methods for the diagnosis and treatment of -related diseases.
Topics: Fusobacterium Infections; Fusobacterium nucleatum; Humans; Mouth Neoplasms; Periodontal Diseases
PubMed: 35186795
DOI: 10.3389/fcimb.2022.815318 -
International Journal of Molecular... Oct 2019Here, we reviewed emerging evidence on the role of the microbial community in colorectal carcinogenesis. A healthy gut microbiota promotes intestinal homeostasis and can... (Review)
Review
Here, we reviewed emerging evidence on the role of the microbial community in colorectal carcinogenesis. A healthy gut microbiota promotes intestinal homeostasis and can exert anti-cancer effects; however, this microbiota also produces a variety of metabolites that are genotoxic and which can negatively influence epithelial cell behaviour. Disturbances in the normal microbial balance, known as dysbiosis, are frequently observed in colorectal cancer (CRC) patients. Microbial species linked to CRC include certain strains of , and amongst others. Whether these microbes are merely passive dwellers exploiting the tumour environment, or rather, active protagonists in the carcinogenic process is the subject of much research. The incidence of chemically-induced tumours in mice models varies, depending upon the presence or absence of these microorganisms, thus strongly suggesting influences on disease causation. Putative mechanistic explanations differentially link these strains to DNA damage, inflammation, aberrant cell behaviour and immune suppression. In the future, modulating the composition and metabolic activity of this microbial community may have a role in prevention and therapy.
Topics: Animals; Bacteroides; Colorectal Neoplasms; DNA Damage; Fusobacterium; Gastrointestinal Microbiome; Humans; Inflammation; Streptococcus; Tumor Microenvironment
PubMed: 31653078
DOI: 10.3390/ijms20215295 -
Journal of Dental Research Mar 2024Colorectal cancer (CRC) and periodontitis have recently been related due to the higher incidence of CRC in periodontal patients and the involvement of periodontal...
Colorectal cancer (CRC) and periodontitis have recently been related due to the higher incidence of CRC in periodontal patients and the involvement of periodontal pathogens in carcinogenesis, suggesting that leakage from the oral cavity to the gut occurs. However, the magnitude of this pass-through in healthy individuals is controversial, and the effect that periodontitis could play in it is understudied. To evaluate the rate of bacterial leakage from the oral cavity to the gut, we analyzed the microbial composition of saliva, subgingival plaque, and fecal samples in healthy individuals without gastrointestinal disorders, including 20 periodontitis patients and 20 oral healthy controls, using PacBio full-length 16S rRNA gene sequencing. As expected, we observed a higher abundance of periodontal pathogens in the subgingival plaque and saliva of periodontal patients. In contrast, no significant differences were found between the fecal samples of both groups, implying that gut samples from periodontal patients were not enriched in periodontal pathogens. , a biomarker of CRC, was not found in the fecal samples of any participant. Our study does show a small leakage of some oral bacteria (mainly streptococci) to the gut, regardless of periodontal health status. Future studies should test whether other host factors and/or the preexistence of a gut disorder must be present in addition to periodontitis to promote the colonization of the gut by oral pathogens. The absence of periodontal pathogens in feces supports the idea that these bacteria could be used as biomarkers of intestinal disorders, including CRC.
Topics: Humans; RNA, Ribosomal, 16S; Periodontitis; Bacteria; Dental Plaque; Fusobacterium nucleatum
PubMed: 38193290
DOI: 10.1177/00220345231221709 -
Inflammatory Bowel Diseases Jan 2023Ulcerative colitis (UC) may be exacerbated by Fusobacterium nucleatum (Fn) infection. However, the mechanism underlying Fn-mediated progression of UC has yet to be...
BACKGROUND
Ulcerative colitis (UC) may be exacerbated by Fusobacterium nucleatum (Fn) infection. However, the mechanism underlying Fn-mediated progression of UC has yet to be established. Here, we aimed to establish whether and how Fn-derived extracellular vesicles (Fn-EVs) participate in the development of experimental colitis through microRNAs (miRNAs).
METHODS
EVs were isolated and purified by ultracentrifugation from Fn and Escherichia coli culture supernatants. Differentially expressed miRNAs in control intestinal epithelial cells (IECs) and Fn-EV-treated IECs were identified by miRNA sequencing. EVs were cocultured with IECs or administered to CARD3wt/CARD3-/- mice by gavage to assess inflammatory responses to and the mechanism of action of Fn-EVs.
RESULTS
Fn-EVs promoted upregulation of proinflammatory cytokines (interleukin [IL]-1β, IL-6, tumor necrosis factor α), downregulation of anti-inflammatory IL-10 and intercellular tight junction proteins ZO-1 and occludin, and epithelial barrier dysfunction in IECs. Fn-EVs significantly aggravated experimental colitis in mice associated with Fn-EV-mediated downregulation of miR-574-5p expression and autophagy activation. Blockade of autophagy using chloroquine alleviates barrier damage exacerbated by Fn-EVs in vitro and in vivo. Inhibition of the miR-574-5p/CARD3 axis reduced the severity of colitis, epithelial barrier damage, and autophagy activation induced by Fn-EVs.
CONCLUSIONS
Here, we describe a new mechanism by which Fn-EVs mediate experimental colitis severity through miR-574-5p/CARD3-dependent autophagy activation, providing a novel target for UC monitoring and targeted therapy.
Topics: Animals; Mice; Fusobacterium nucleatum; MicroRNAs; Cytokines; Colitis, Ulcerative; Extracellular Vesicles
PubMed: 35998069
DOI: 10.1093/ibd/izac177 -
Journal of Dairy Science Dec 2019Until 2010, our knowledge of the uterine microbiome in cows that developed uterine disease relied almost exclusively on culture-dependent studies and mostly included... (Review)
Review
Until 2010, our knowledge of the uterine microbiome in cows that developed uterine disease relied almost exclusively on culture-dependent studies and mostly included cows with clinical endometritis (i.e., with purulent uterine discharge). Those studies consistently found a strong positive correlation between Trueperella pyogenes and clinical endometritis, whereas other pathogens such as Escherichia coli, Fusobacterium necrophorum, Prevotella melaninogenica, and Bacteroides spp. were also commonly cocultured. In contrast, Streptococcus spp., Staphylococcus spp., and Bacillus spp. were usually isolated from healthy cows. Starting in 2010, culture-independent studies using PCR explored the microbiome of cows with metritis and clinical endometritis, and observed that E. coli was a pioneer pathogen that predisposed cows to infection with F. necrophorum, which was strongly associated with metritis, and to infection with T. pyogenes, which was strongly associated with clinical endometritis. Starting in 2011, culture-independent studies using metagenomic sequencing expanded our knowledge of the uterine microbiome. It has been shown that cows have bacteria in the uterus even before calving, they have an established uterine microbiome within 20 min of calving, and that the microbiome structure is identical between cows that develop metritis and healthy cows until 2 d postpartum, after which the bacterial structure of cows that developed metritis deviates in favor of greater relative abundance of Bacteroidetes and Fusobacteria and lesser relative abundance of Proteobacteria and Tenericutes. The shift in the uterine microbiome in cows that develop metritis is characterized by a loss of heterogeneity and a decrease in bacterial richness. At the genus level, Bacteroides, Porphyromonas, and Fusobacterium have the strongest association with metritis. At the species level, we observed that Bacteroides pyogenes, Porphyromonas levii, and Helcococcus ovis were potential emerging uterine pathogens. Finally, we have shown that the hematogenous route is a viable route of uterine infection with uterine pathogens. Herein, we propose that metritis is associated with a dysbiosis of the uterine microbiota characterized by decreased richness, and an increase in Bacteroidetes and Fusobacteria, particularly Bacteroides, Porphyromonas, and Fusobacterium.
Topics: Animals; Bacteria; Bacteroidetes; Cattle; Cattle Diseases; Dysbiosis; Endometritis; Female; Fusobacteria; Microbiota; Polymerase Chain Reaction; Postpartum Period; Uterine Diseases; Uterus
PubMed: 31587913
DOI: 10.3168/jds.2019-17106 -
Frontiers in Immunology 2022() is originally an oral opportunistic pathogen and accumulating evidence links the presence of with the pathogenicity, development, and prognosis of colorectal cancer... (Review)
Review
() is originally an oral opportunistic pathogen and accumulating evidence links the presence of with the pathogenicity, development, and prognosis of colorectal cancer (CRC). However, only limited preliminary data is available dealing with the role of in other malignancies except for CRC. The present review aims to update and systematize the latest information about the mechanisms of -mediating carcinogenesis, together with the detection rates, clinicopathological, and molecular features in -associated malignancies. Comparing with adjacent non-tumorous tissue, previous studies have shown an overabundance of intratumoural . Although the prognostic role of is still controversial, a higher prevalence of was usually associated with a more advanced tumor stage and a worse overall survival. Preliminary evidence have shown that epithelial-to-mesenchymal transition (EMT) and relevant inflammation and immune response aroused by may be the probable link between infection and the initiation of oral/head and neck cancer. Further studies are needed to elucidate the etiologic role of the specific microbiota and the connection between the extent of periodontitis and carcinogenesis in different tumor types. The mechanisms of how the antibiotics exerts the critical role in the carcinogenesis and antitumor effects in malignancies other than CRC need to be further explored.
Topics: Carcinogenesis; Colorectal Neoplasms; Fusobacterium Infections; Fusobacterium nucleatum; Humans; Prognosis
PubMed: 36059542
DOI: 10.3389/fimmu.2022.968649 -
Archives of Biochemistry and Biophysics Jul 2023The opportunistic oral pathogen, Fusobacterium nucleatum contains meso-lanthionine as the diaminodicarboxylic acid in the pentapeptide crosslink of the peptidoglycan...
The opportunistic oral pathogen, Fusobacterium nucleatum contains meso-lanthionine as the diaminodicarboxylic acid in the pentapeptide crosslink of the peptidoglycan layer. The diastereomer, l,l-lanthionine is formed by lanthionine synthase, a PLP-dependent enzyme that catalyzes the β-replacement of l-cysteine with a second equivalent of l-cysteine. In this study, we explored possible enzymatic mechanisms for the formation of meso-lanthionine. Our inhibition studies with lanthionine synthase, described herein, revealed that meso-diaminopimelate, a bioisostere of meso-lanthionine, is a more potent inhibitor of lanthionine synthase compared to the diastereomer, l,l-diaminopimelate. These results suggested that lanthionine synthase could also form meso-lanthionine by the β-replacement of l-cysteine with d-cysteine. Through steady-state and pre-steady state kinetic analysis, we confirm that d-cysteine reacts with the ⍺-aminoacylate intermediate with a k that was 2-3-fold faster and K value that was 2-3fold lower compared to l-cysteine. However, given that intracellular levels of d-cysteine levels are assumed to be significantly lower than that of l-cysteine, we also determined if the gene product, FN1732, with low sequence identity to diaminopimelate epimerase could convert l,l-lanthionine to meso-lanthionine. Using diaminopimelate dehydrogenase in a coupled spectrophotometric assay, we show that FN1732 can convert l,l-lanthionine to meso-lanthionine with a k of 0.07 ± 0.001 s and a K of 1.9 ± 0.1 mM. In summary, our results provide two possible enzymatic mechanisms for the biosynthesis of meso-lanthionine in F. nucleatum.
Topics: Fusobacterium nucleatum; Cysteine; Kinetics; Sulfides
PubMed: 37329940
DOI: 10.1016/j.abb.2023.109666 -
Oncology Letters May 2024Liver metastasis is a major cause of mortality in patients with advanced stages of colorectal cancer (CRC). The gut microbiota has been demonstrated to influence the...
Liver metastasis is a major cause of mortality in patients with advanced stages of colorectal cancer (CRC). The gut microbiota has been demonstrated to influence the progression of liver diseases, potentially providing novel perspectives for diagnosis, treatment and research. However, the gut microbial characteristics in CRC with liver metastasis (LM) and with no liver metastasis (NLM) have not yet been fully established. In the present study, high-throughput 16S RNA sequencing technology was employed, in order to examine the gut microbial richness and composition in patients with CRC with LM or NLM. A discovery cohort (cohort 2; LM=18; NLM=36) and a validation cohort (cohort 3; LM=13; NLM=41) were established using fresh feces. In addition, primary carcinoma tissue samples were also analyzed (LM=8 and NLM=10) as a supplementary discovery cohort (cohort 1). The findings of the present study indicated that the intestinal microbiota richness and diversity were increased in the LM group as compared to the NLM group. A significant difference was observed in species composition between the LM and NLM group. In the two discovery cohorts with two different samples, the dominant phyla were consistent, but varied at lower taxonomic levels. Phylum Fusobacteria presented consistent and significant enrichment in LM group in both discovery cohorts. Furthermore, with the application of a random forest model and receiver operator characteristic curve analysis, Fusobacteria was identified as a potential biomarker for LM. Moreover, Fusobacteria was also a poor prognosis factor for survival. Importantly, the findings were reconfirmed in the validation cohort. On the whole, the findings of the present study demonstrated that CRC with LM and NLM exhibit distinct gut microbiota characteristics. Fusobacteria detection thus has potential for use in predicting LM and a poor prognosis of patients with CRC.
PubMed: 38596264
DOI: 10.3892/ol.2024.14368 -
Voprosy Pitaniia 2023The oral microbiome is a community of symbiotic, commensal and opportunistic microorganisms, usually present in the form of biofilm, that plays a critical role in... (Review)
Review
The oral microbiome is a community of symbiotic, commensal and opportunistic microorganisms, usually present in the form of biofilm, that plays a critical role in maintaining the homeostasis and protective function of the oral cavity. Recently, the study of the human oral microbiome to develop new diagnostic and therapeutic approaches has become a promising new area of the research in the field of personalized medicine. of this review was to generalise and analyse the accumulated data on the relationship between the oral microbiome characteristics and the course of systemic diseases. . Literature searches were performed using RSCI, PubMed, Google Scholar, and included original research data published mainly in the last 5 years. . The review summarized data on the role of the oral microbiome in the development of a number of systemic diseases, including alimentary diseases. The importance of the major exogenous and endogenous factors that lead to changes in the oral microbiome, including diet, macro- and micronutrient composition of foods, was highlighted. Data were provided on the main types of microorganisms associated with the development and c ourse of a number of somatic diseases, represented mainly by obligate anaerobic periodontal pathogens (Tannerella forsythia, Treponema denticola, Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans). The role of the systemic inflammatory response as the main pathogenetic factor of oral dysbiosis has been described. The benefits of periodontal therapy in metabolic disorders such as diabetes mellitus, obesity, and dyslipidemia have been discussed. Promising approaches to correct oral dysbiosis have been presented. . The knowledge of the relationships between the oral microbiome composition, the development and characteristics of the course of somatic disease can contribute to the development of new technologies for its prevention and treatment. The change in the structure of the oral microbiome observed in systemic diseases is usually accompanied by a decrease in bacterial diversity and an increase in the number of pathogenic bacteria. Lifestyle modification, dietary therapy, smoking cessation, rational use of antibacterial drugs and treatment of periodontitis play an important role in normalising the structure of the oral microbiome.
Topics: Humans; Dysbiosis; Porphyromonas gingivalis; Prevotella intermedia; Fusobacterium nucleatum
PubMed: 37801450
DOI: 10.33029/0042-8833-2023-92-4-6-19