-
MBio Apr 2021Aspirin is a chemopreventive agent for colorectal adenoma and cancer (CRC) that, like many drugs inclusive of chemotherapeutics, has been investigated for its effects on...
Aspirin is a chemopreventive agent for colorectal adenoma and cancer (CRC) that, like many drugs inclusive of chemotherapeutics, has been investigated for its effects on bacterial growth and virulence gene expression. Given the evolving recognition of the roles for bacteria in CRC, in this work, we investigate the effects of aspirin with a focus on one oncomicrobe- We show that aspirin and its primary metabolite salicylic acid alter strain Fn7-1 growth in culture and that aspirin can effectively kill both actively growing and stationary Fn7-1. We also demonstrate that, at levels that do not inhibit growth, aspirin influences Fn7-1 gene expression. To assess whether aspirin modulation of may be relevant , we use the mouse intestinal tumor model in which Fn7-1 is orally inoculated daily to reveal that aspirin-supplemented chow is sufficient to inhibit -potentiated colonic tumorigenesis. We expand our characterization of aspirin sensitivity across other strains, including those isolated from human CRC tissues, as well as other CRC-associated microbes, enterotoxigenic , and colibactin-producing Finally, we determine that individuals who use aspirin daily have lower fusobacterial abundance in colon adenoma tissues, as determined by quantitative PCR performed on adenoma DNA. Together, our data support that aspirin has direct antibiotic activity against strains and suggest that consideration of the potential effects of aspirin on the microbiome holds promise in optimizing risk-benefit assessments for use of aspirin in CRC prevention and management. There is an increasing understanding of the clinical correlations and potential mechanistic roles of specific members of the gut and tumoral microbiota in colorectal cancer (CRC) initiation, progression, and survival. However, we have yet to parlay this knowledge into better CRC outcomes through microbially informed diagnostic, preventive, or therapeutic approaches. Here, we demonstrate that aspirin, an established CRC chemopreventive, exhibits specific effects on the CRC-associated in culture, an animal model of intestinal tumorigenesis, and in human colonic adenoma tissues. Our work proposes a potential role for aspirin in influencing CRC-associated bacteria to prevent colorectal adenomas and cancer, beyond aspirin's canonical anti-inflammatory role targeting host tissues. Future research, such as studies investigating the effects of aspirin on fusobacterial load in patients, will help further elucidate the prospect of using aspirin to modulate for improving CRC outcomes.
Topics: Adenoma; Animals; Aspirin; Bacteria; Carcinogenesis; Cell Transformation, Neoplastic; Colon; Colorectal Neoplasms; Female; Fusobacterium nucleatum; Humans; Male; Mice
PubMed: 33824205
DOI: 10.1128/mBio.00547-21 -
Archives of Oral Biology Oct 2022This study aimed to clarify the antibacterial mechanism and antibiofilm effect of soybean-derived peptide BCBS-11 against periodontopathic bacteria.
OBJECTIVE
This study aimed to clarify the antibacterial mechanism and antibiofilm effect of soybean-derived peptide BCBS-11 against periodontopathic bacteria.
DESIGN
The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of BCBS-11 against Porphyromonas gingivalis (P. gingivalis), Fusobacterium nucleatum (F. nucleatum), and Streptococcus mitis (S. mitis) were determined for the antibacterial mechanism. The effect of BCBS-11 on membrane permeability and depolarization activity were investigated using propidium iodide (PI) staining and 3, 3'-dipropylthiadicarbocyanine iodide (DiSC-(5)) analysis. Monospecies and multispecies biofilms were cultured on 96-well plates. The amount of biofilm was determined using crystal violet staining to determine the inhibition of biofilm formation and the eradication of established biofilm using BCBS-11. The cytotoxicity of BCBS-11 was evaluated using 3-(4, 5-Dimethylthiazol-2-yl)- 2, 5-diphenyltetrazolium bromide (MTT) assay.
RESULTS
The MIC and MBC indicated the bactericidal activity of BCBS-11 against P. gingivalis and F. nucleatum. The PI staining revealed that BCBS-11 disrupted the bacterial membrane integrity. The DiSC-(5) analysis indicated that BCBS-11 depolarized the bacterial cytoplasmic membrane. These results indicate the antimicrobial action of BCBS-11 through membrane disruption and the collapse of membrane electrochemical gradient. BCBS-11 significantly inhibited the monospecies biofilm formation of P. gingivalis and F. nucleatum and also inhibited dual-species biofilm. BCBS-11 was not cytotoxic toward human oral epithelial cells.
CONCLUSIONS
BCBS-11 inhibits the monospecies and multispecies biofilm formation of P. gingivalis and F. nucleatum, and their bactericidal activity results from membrane disruption.
Topics: Anti-Bacterial Agents; Biofilms; Fusobacterium nucleatum; Humans; Peptides; Porphyromonas gingivalis; Glycine max
PubMed: 35849907
DOI: 10.1016/j.archoralbio.2022.105497 -
Analytical Biochemistry Sep 2020Fusobacterium nucleatum. nucleatum (Fn.n) is associated with colorectal carcinoma. A highly sensitive fluorescence quenching-recovery detection platform based on rolling... (Review)
Review
Fusobacterium nucleatum. nucleatum (Fn.n) is associated with colorectal carcinoma. A highly sensitive fluorescence quenching-recovery detection platform based on rolling circle amplification and hairpin molecular beacon technology for the specific analysis of Fn.n, hairpin MB being used to achieve double quenching. First, a specific recognition sequence target in the padlock probe was designed based on the nusG specific gene of Fn.n. The padlock probe then formed circular DNA using the ligase. After digestion, linear amplification was achieved by the phi29 DNA polymerase and the RCA primer, and a large amount of amplified products was obtained. Subsequently, the amplification products hybridized with the signal probe, leading to the opening of the hairpin structure in MBs. As a result, FAM at 5' end and BHQ-1 at 3' end became separated, which allowed for the recovery of the fluorescence signal. The proposed method showed high sensitivity and specificity for the detection of Fn.n genomic DNA (LOD as low as 0.7 ng L) and performed well in the identification of this bacteria in real samples.
Topics: Biosensing Techniques; Colorectal Neoplasms; DNA, Bacterial; Feces; Female; Fusobacterium nucleatum; Humans; Male; Spectrometry, Fluorescence
PubMed: 32622974
DOI: 10.1016/j.ab.2020.113808 -
Medicina Oral, Patologia Oral Y Cirugia... Sep 2023Studies try to explain the hypothesis that maternal periodontitis may be associated with preterm birth.
BACKGROUND
Studies try to explain the hypothesis that maternal periodontitis may be associated with preterm birth.
MATERIAL AND METHODS
This is a case-control study with 120, 40 cases (gestational age <37 weeks) and 80 controls (gestational age ≥37 weeks), that were submitted to the clinical periodontal examination and subgingival biofilm collection. Bacterial DNA of subgingival biofilm was performed and processed by qPCR.
RESULTS
Periodontitis was statistically significant in the Case group (35%) when compared to the Control group (11.2%) and Gingival Bleeding Index (GBI), sites with PS ≥ 4mm and sites with CAL ≥ 5mm were statistically higher in the Case group (p < 0.05). The proportions of Pi (p = 0.026) and Fn (p = 0.041) of subgingival biofilm were higher in the Case group. A greater number of sites with PS ≥ 4mm (r = -0.202; p = 0.026) and CAL ≥ 5mm (r = -0.322; p < 0.001) were correlated to lower gestational age.
CONCLUSIONS
Periodontitis, preterm delivery, and/or low birth weight may have a possible relationship based on clinical parameters and the ratio of Pi and Fn at periodontal sites.
Topics: Infant, Newborn; Humans; Female; Infant; Fusobacterium nucleatum; Prevotella; Case-Control Studies; Premature Birth; Periodontitis
PubMed: 37622431
DOI: 10.4317/medoral.25874 -
OncoTargets and Therapy 2022There is a major limitation in the immunotherapy for solid cancer is that it only benefited a minority of cancer patients. This study aims to investigate whether the...
PURPOSE
There is a major limitation in the immunotherapy for solid cancer is that it only benefited a minority of cancer patients. This study aims to investigate whether the differential composition of the lung microbiome could affect the sustained clinical responses in lung cancers treated with immunotherapy.
METHODS
Twenty-seven non-responders and 19 responders treated with anti-PD-1 therapy were included in the discovery set. Bacterial load in bronchoalveolar lavage from lung cancer patients was examined by quantitative PCR of 16S rRNA copies. Bacterial 16S rDNA was sequenced using the Illumina HiSeq on the 16S rDNA V3-V4 variable region. Operational taxonomic unit (OTU) analysis was performed using VSEARCH v2. The α-diversity and β-diversity were calculated using QIIME software.
RESULTS
The mean copy number of bacterial 16S DNA levels significantly decreased after anti-PD-1 treatment (after: 1.8 ± 0.6×10 copies per milliliter vs prior to treatment: 3.3 ± 1.1x10, p = 0.0036). In addition, longitudinal analysis revealed that microbial diversity was reduced taxonomically after treatment compared to those prior to the treatment (Shannon values: before: 3.291 ± 0.067 vs after: 2.668 ± 0.168, p < 0.01). Further, we observed a reduction of , including phylum (p < 0.01), class (p < 0.01), order (p < 0.01), family (p < 0.01), genus (p = 0.025) in the responders post anti-PD-1 treatment. However, there was no significant difference of in non-responders. An independent cohort was used to validate the levels of , demonstrating that patients with higher abundance of prior to treatment were significantly more likely to have poor response to anti-PD-1 therapy (p < 0.001).
CONCLUSION
Airway enriched prior to anti-PD-1 therapy is associated with poor response in lung cancer, which indicated that potential resistance to immunotherapy can be attributed to lung microbiome.
PubMed: 35250279
DOI: 10.2147/OTT.S348382 -
BMC Oral Health May 2021Periodontal disease represents a major health concern. The administration of beneficial microbes has been increasing in popularity over efforts to manipulate the...
BACKGROUND
Periodontal disease represents a major health concern. The administration of beneficial microbes has been increasing in popularity over efforts to manipulate the microbes using antimicrobial agents. This study determined the ability of Streptococcus salivarius to inhibit IL-6 and IL-8 production by gingival fibroblasts when activated by periodontal pathogens and their effect on the salivary microbiome.
METHODS
Primary human gingival fibroblasts were challenged with Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum and a combination of all three. IL-6 and IL-8 cytokine release were measured. Using this same model, S. salivarius K12, M18 and different supernatant and whole-cell lysate fractions of S. salivarius K12 were administered to pathogen-induced fibroblasts. A patient study of healthy participants was also conducted to determine the effect S. salivarius K12 had on the native microbiome using 16S next generation sequence analysis.
RESULTS
All pathogens tested induced a significant IL-6 and IL-8 response. S. salivarius K12 or M18, did not exhibit an increase in inflammatory cytokines. When either of the probiotic strains were co-administered with a pathogen, there were significant reductions in both IL-6 and IL-8 release. This effect was also observed when gingival fibroblasts were pre-treated with either S. salivarius K12 or M18 and then stimulated with the oral pathogens. Chewing gum containing S. salivarius K12 did not alter the salivary microbiome and did not increase inflammatory markers in the oral cavity.
CONCLUSION
S. salivarius K12 and M18 prevented immune activation induced by periodontal disease pathogens. S. salivarius K12 did not alter the salivary microbiome or induce immune activation when administered as a chewing gum. These results warrant further study to determine if it may be an effective treatment in a model of periodontal disease.
Topics: Aggregatibacter actinomycetemcomitans; Fusobacterium nucleatum; Humans; Periodontal Diseases; Porphyromonas gingivalis; Streptococcus salivarius
PubMed: 33962608
DOI: 10.1186/s12903-021-01606-z -
Microbial Pathogenesis Dec 2021The eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) play a substantial role in Periodontal Disease (PD) due to their antimicrobial and immunomodulatory actions....
The eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) play a substantial role in Periodontal Disease (PD) due to their antimicrobial and immunomodulatory actions. However, their antimicrobial mechanism of action against bacteria involved in PD remains unclear. We aimed to estimate the probable targets of EPA and DHA against the seven periodontopathogens. Through in silico analyses, the protein-acids interactions, protein characterization, and molecular docking were performed. We identified 165 proteins from periodontopathogens that may interact with EPA and DHA. Fusobacterium nucleatum has the highest number of predicted proteins among analyzed bacteria (n = 43, 26.06%). The EPA shows more interactions than DHA. The EPA and DHA interact mainly with proteins involved in the metabolism (n = 69, 41.81%). Also, the EPA and DHA interact with proteins located in any subcellular location. The affinities between acids and pathogenic proteins were moderate (binding energy was lower than -4.0 kcal/mol). The interactions between EPA and DHA and periodontopathogens occur in multiples proteins. There is not a predilection about the functional class of pathogenic proteins targeting EPA and DHA. However, there are moderate binding affinities between EPA or DHA and essential pathogenic proteins (TolC, CRISPR, FusA).
Topics: Anti-Bacterial Agents; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fusobacterium nucleatum; Molecular Docking Simulation
PubMed: 34699926
DOI: 10.1016/j.micpath.2021.105266 -
Journal of Periodontology Sep 2019This study evaluated the effects of topical administration of Bdellovibrio bacteriovorus HD100 on experimental periodontitis (EP) in rats.
BACKGROUND
This study evaluated the effects of topical administration of Bdellovibrio bacteriovorus HD100 on experimental periodontitis (EP) in rats.
METHODS
Thirty-two rats were divided into groups C (control), EP, C-HD100, and EP-HD100. At day 0, animals of groups EP and EP-HD100 received cotton ligatures around mandibular first molars (MFM). In groups C-HD100 and EP-HD100, 1 mL of suspensions containing B. bacteriovorus HD100 was topically administered in the subgingival region of MFMs at days 0, 3, and 7. Animals were euthanized at day 14. Gingival tissue, hemimandibles, and oral biofilm were collected. Data were statistically analyzed.
RESULTS
Group EP-HD100 presented greater bone volume and lower connective tissue attachment loss (CTAL) than group EP (P < 0.05). Group EP-HD100 presented greater proportions of Actinomyces and Streptococcus-like species and lower proportions of Prevotella intermedia, Peptostreptococcus micros, Fusobacterium nucleatum, Fusobacterium polymorphum, Eikenella corrodens, Eubacterium nodatum, Campylobacter gracilis, Capnocytophaga sputigena, and Veillonella parvula-like species than group EP. Group EP-HD100 presented greater levels of osteoprotegerin and gene expression of interleukin (IL)-17, IL-10, and forkhead box P3 than group EP (P < 0.05).
CONCLUSION
Topical use of B. bacteriovorus HD100 promotes a protective effect against alveolar bone loss and CTAL in rats with EP.
Topics: Animals; Bacteria; Fusobacterium nucleatum; Periodontitis; Prevotella intermedia; Rats; Veillonella
PubMed: 30828815
DOI: 10.1002/JPER.18-0485 -
Genome Biology Jun 2021A critical challenge in microbiome data analysis is the existence of many non-biological zeros, which distort taxon abundance distributions, complicate data analysis,...
A critical challenge in microbiome data analysis is the existence of many non-biological zeros, which distort taxon abundance distributions, complicate data analysis, and jeopardize the reliability of scientific discoveries. To address this issue, we propose the first imputation method for microbiome data-mbImpute-to identify and recover likely non-biological zeros by borrowing information jointly from similar samples, similar taxa, and optional metadata including sample covariates and taxon phylogeny. We demonstrate that mbImpute improves the power of identifying disease-related taxa from microbiome data of type 2 diabetes and colorectal cancer, and mbImpute preserves non-zero distributions of taxa abundances.
Topics: Actinobacteria; Bacteroidetes; Case-Control Studies; Colorectal Neoplasms; DNA, Bacterial; Diabetes Mellitus, Type 2; Firmicutes; Fusobacteria; Humans; Metagenome; Microbiota; Phylogeny; Polymerase Chain Reaction; Proteobacteria; RNA, Ribosomal, 16S; Software; Whole Genome Sequencing
PubMed: 34183041
DOI: 10.1186/s13059-021-02400-4 -
Journal of Applied Microbiology Jan 2023Periodontitis is an inflammatory disease caused by microbial infections of the gum. At an advanced stage, periodontitis can even destroy the alveolar bone. Fusobacterium... (Review)
Review
Periodontitis is an inflammatory disease caused by microbial infections of the gum. At an advanced stage, periodontitis can even destroy the alveolar bone. Fusobacterium nucleatum, Prevotella intermedia, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Capnocytophaga gingivalis, and Pr. nigrescens are the major pathogens in periodontitis. Scaling and root planning are used together with local or systemic antibiotics to treat periodontitis. The difficulty in complete eradication of periodontal pathogens frequently leads to the relapse of the disease. As not many new antibiotics are available in the market, many researchers are now focusing on developing alternative strategies against periodontal microbes. This review provides an overview of the possible use of bacteriophages, lysins, honey, plant extracts, metallic salts, nanoparticles, and vaccines as alternative therapeutic agents against periodontal infections. The information provided here could help in designing alternative therapeutics for the treatment of periodontal infections.
Topics: Humans; Periodontitis; Porphyromonas gingivalis; Prevotella intermedia; Fusobacterium nucleatum; Disease Management; Aggregatibacter actinomycetemcomitans
PubMed: 36724261
DOI: 10.1093/jambio/lxac039