-
Signal Transduction and Targeted Therapy May 2024
Topics: Colorectal Neoplasms; Humans; Fusobacterium
PubMed: 38719840
DOI: 10.1038/s41392-024-01844-x -
Poultry Science Jul 2024This study aimed to evaluate the effect of low molecular weight Acanthopanax polysaccharides on simulated digestion, probiotics, and intestinal flora of broilers in...
Prebiotic characteristics of degraded polysaccharides from Acanthopanax senticosus polysaccharide on broilers gut microbiota based on in vitro digestion and fecal fermentation.
This study aimed to evaluate the effect of low molecular weight Acanthopanax polysaccharides on simulated digestion, probiotics, and intestinal flora of broilers in vitro. The experiments were carried out by HO-Vc degradation of Acanthopanax polysaccharides, in vitro simulated digestion to evaluate the digestive performance of polysaccharides with different molecular weights, in vitro probiotic evaluation of the probiotic effect of polysaccharides on lactobacilli and bifidobacteria, in vitro anaerobic fermentation and high-throughput sequencing of 16S rRNA genes to study the impact of Acanthopanax polysaccharides on the intestinal flora of broilers, and the effect of Acanthopanax polysaccharides on the short-chain fatty acids of intestines were determined by GC-MS method. The results showed that the molecular weight of Acanthopanax polysaccharide (ASPS) was 9,543 Da, and the molecular weights of polysaccharides ASPS-1 and ASPS-2 were reduced to 4,288 Da and 3,822 Da after degradation, and the particle sizes, PDIs, and viscosities were also significantly decreased. ASPS-1 has anti-digestive properties and better in vitro probiotic properties. The addition of ASPS-1 regulates the structure of intestinal microorganisms by regulating fecalibacterium to produce short-chain fatty acids, promoting the colonization of beneficial bacteria such as fecalibacterium, paraprevotella and diminishing the prevalence of detrimental bacteria such as Fusobacteria. Interestingly the ASPS-1 group found higher levels of Paraprevotella, which degraded trypsin in the gut, reducing inflammation, acted as a gut protector, and was influential in increasing the levels of acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and total SCFAs in the fermented feces. Therefore, the degraded ASPS-1 can better regulate the structure of intestinal flora and promote the production of SCFAs, creating possibilities for its use as a potential prebiotic, which is conducive to the intestinal health of poultry.
Topics: Animals; Gastrointestinal Microbiome; Chickens; Eleutherococcus; Polysaccharides; Prebiotics; Feces; Digestion; Fermentation; Animal Feed; Diet; Fatty Acids, Volatile
PubMed: 38713991
DOI: 10.1016/j.psj.2024.103807 -
Gut Microbes 2024Mucinous colorectal cancer (CRC) is a common histological subtype of colorectal adenocarcinoma, associated with a poor response to chemoradiotherapy. The commensal...
Mucinous colorectal cancer (CRC) is a common histological subtype of colorectal adenocarcinoma, associated with a poor response to chemoradiotherapy. The commensal facultative anaerobes fusobacteria, have been associated with poor prognosis specifically in mesenchymal CRC. Interestingly, fusobacterial infection is especially prevalent in mucinous CRC. The objective of this study was therefore to increase our understanding of beneficial and detrimental effects of fusobacterial infection, by contrasting host cell signaling and immune responses in areas of high vs. low infection, using mucinous rectal cancer as a clinically relevant example. We employed spatial transcriptomic profiling of 106 regions of interest from 8 mucinous rectal cancer samples to study gene expression in the epithelial and immune segments across regions of high versus low fusobacterial infection. Fusobacteria high regions were associated with increased oxidative stress, DNA damage, and P53 signaling. Meanwhile regions of low fusobacterial prevalence were characterized by elevated JAK-STAT, Il-17, Il-1, chemokine and TNF signaling. Immune masks within fusobacterial high regions were characterized by elevated proportions of cytotoxic (CD8+) T cells ( = 0.037), natural killer (NK) cells ( < 0.001), B-cells ( < 0.001), and gamma delta T cells ( = 0.003). Meanwhile, fusobacteria low regions were associated with significantly greater M2 macrophage ( < 0.001), fibroblast ( < 0.001), pericyte ( = 0.002), and endothelial ( < 0.001) counts.
Topics: Humans; Rectal Neoplasms; Signal Transduction; DNA Damage; Gene Expression Profiling; Male; Female; Middle Aged; Transcriptome; Aged
PubMed: 38709233
DOI: 10.1080/19490976.2024.2350149 -
BMC Oral Health May 2024To evaluate the antibacterial effectiveness of a combination of ε-poly-L-lysine (ε-PL), funme peptide (FP) as well as domiphen against oral pathogens, and assess the... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the antibacterial effectiveness of a combination of ε-poly-L-lysine (ε-PL), funme peptide (FP) as well as domiphen against oral pathogens, and assess the efficacy of a BOP® mouthwash supplemented with this combination in reducing halitosis and supragingival plaque in a clinical trial.
MATERIALS AND METHODS
The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the compound against Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans were determined by the gradient dilution method. Subsequently, the CCK-8 assay was used to detect the toxicity of mouthwash on human gingival fibroblastst, and the effectiveness in reducing halitosis and supragingival plaque of the mouthwash supplemented with the combination was analyzed by a randomized, double-blind, parallel-controlled clinical trial.
RESULTS
The combination exhibited significant inhibitory effects on tested oral pathogens with the MIC < 1.56% (v/v) and the MBC < 3.13% (v/v), and the mouthwash containing this combination did not inhibit the viability of human gingival fibroblasts at the test concentrations. The clinical trial showed that the test group displayed notably lower volatile sulfur compounds (VSCs) at 0, 10, 24 h, and 7 d post-mouthwash (P < 0.05), compared with the baseline. After 7 days, the VSC levels of the and control groups were reduced by 50.27% and 32.12%, respectively, and notably cutting severe halitosis by 57.03% in the test group. Additionally, the Plaque Index (PLI) of the test and control group decreased by 54.55% and 8.38%, respectively, and there was a significant difference in PLI between the two groups after 7 days (P < 0.01).
CONCLUSIONS
The combination of ε-PL, FP and domiphen demonstrated potent inhibitory and bactericidal effects against the tested oral pathogens, and the newly formulated mouthwash added with the combination exhibited anti-dental plaque and anti-halitosis properties in a clinical trial and was safe.
TRIAL REGISTRATION
The randomized controlled clinical trial was registered on Chinese Clinical Trial Registry (No. ChiCTR2300073816, Date: 21/07/2023).
Topics: Humans; Halitosis; Mouthwashes; Dental Plaque; Double-Blind Method; Male; Female; Polylysine; Adult; Microbial Sensitivity Tests; Young Adult; Anti-Bacterial Agents; Porphyromonas gingivalis; Fusobacterium nucleatum; Fibroblasts; Peptides; Aggregatibacter actinomycetemcomitans; Streptococcus mutans
PubMed: 38702623
DOI: 10.1186/s12903-024-04255-0 -
Archives of Microbiology May 2024Aggregatibacter actinomycetemcomitans is an opportunistic Gram-negative periodontopathogen strongly associated with periodontitis and infective endocarditis. Recent... (Comparative Study)
Comparative Study
Aggregatibacter actinomycetemcomitans is an opportunistic Gram-negative periodontopathogen strongly associated with periodontitis and infective endocarditis. Recent evidence suggests that periodontopathogens can influence the initiation and progression of oral squamous cell carcinoma (OSCC). Herein we aimed to investigate the effect of A. actinomycetemcomitans-derived extracellular vesicles (EVs) on OSCC cell behavior compared with EVs from periodontopathogens known to associate with carcinogenesis. EVs were isolated from: A. actinomycetemcomitans and its mutant strains lacking the cytolethal distending toxin (CDT) or lipopolysaccharide (LPS) O-antigen; Porphyromonas gingivalis; Fusobacterium nucleatum; and Parvimonas micra. The effect of EVs on primary and metastatic OSCC cells was assessed using cell proliferation, apoptosis, migration, invasion, and tubulogenesis assays. A. actinomycetemcomitans-derived EVs reduced the metastatic cancer cell proliferation, invasion, tubulogenesis, and increased apoptosis, mostly in CDT- and LPS O-antigen-dependent manner. EVs from F. nucleatum impaired the metastatic cancer cell proliferation and induced the apoptosis rates in all OSCC cell lines. EVs enhanced cancer cell migration regardless of bacterial species. In sum, this is the first study demonstrating the influence of A. actinomycetemcomitans-derived EVs on oral cancer in comparison with other periodontopathogens. Our findings revealed a potential antitumorigenic effect of these EVs on metastatic OSCC cells, which warrants further in vivo investigations.
Topics: Aggregatibacter actinomycetemcomitans; Extracellular Vesicles; Mouth Neoplasms; Humans; Cell Line, Tumor; Apoptosis; Cell Proliferation; Cell Movement; Fusobacterium nucleatum; Carcinoma, Squamous Cell; Porphyromonas gingivalis
PubMed: 38702412
DOI: 10.1007/s00203-024-03976-8 -
Heliyon May 2024While the 5-year survival rate of patients with advanced non-small cell lung cancer (NSCLC) has seen some improvement, the majority of NSCLC patients fail to respond to...
While the 5-year survival rate of patients with advanced non-small cell lung cancer (NSCLC) has seen some improvement, the majority of NSCLC patients fail to respond to immunotherapy with immune checkpoint inhibitors (ICIs). It is critical to identify effective biomarkers that can enhance the efficacy of immunotherapy. The clinical data in the current study were collected from NSCLC patients treated with ICIs, and two groups were classified according to treatment effect: good group with consistent efficacy, poor group with only progressiveness. Differences in intestinal microbiota between the two groups were analyzed using 16s rRNA sequencing. Beta diversity analysis indicated differences between the two groups that were available for differentiation. Comparison of the number of common or unique operational taxonomic units (OTUs) among different groups suggested that there were 53 unique OTUs in the good group and 51 unique OTUs in the poor group. At the phylum level, there was a difference between the two groups for several bacterial groups with the highest abundance values, among which and were more abundant in the good group. Members of the genera and were abundant in the good group, while the abundance of was low. Biomarkers in the poor group included and . The intestinal microbiota composition affected the immunotherapy process for NSCLC, which might offer more rational instructions for the clinical application of ICIs in NSCLC patients.
PubMed: 38699020
DOI: 10.1016/j.heliyon.2024.e29899 -
BMC Oral Health May 2024Fusobacterium nucleatum (F. nucleatum) is a microbial risk factor whose presence increases the risk of oral squamous cell carcinoma (OSCC) progression. However, whether...
BACKGROUND
Fusobacterium nucleatum (F. nucleatum) is a microbial risk factor whose presence increases the risk of oral squamous cell carcinoma (OSCC) progression. However, whether it can promote the proliferation of OSCC cells remains unknown.
METHODS
In this study, we investigated F. nucleatum effect on OSCC cell proliferation using in vitro and in vivo experiments.
RESULTS
Our results showed that F. nucleatum promoted OSCC cell proliferation, doubling the cell count after 72 h (CCK-8 assay). Cell cycle analysis revealed G2/M phase arrest. F. nucleatum interaction with CDH1 triggered phosphorylation, upregulating downstream protein β-catenin and activating cyclinD1 and Myc. Notably, F. nucleatum did not affect noncancerous cells, unrelated to CDH1 expression levels in CAL27 cells. Overexpression of phosphorylated CDH1 in 293T cells did not upregulate β-catenin and cycle-related genes. In vivo BALB/c nude experiments showed increased tumor volume and Ki-67 proliferation index after F. nucleatum intervention.
CONCLUSION
Our study suggests that F. nucleatum promotes OSCC cell proliferation through the CDH1/β-catenin pathway, advancing our understanding of its role in OSCC progression and highlighting its potential as a therapeutic target.
Topics: Fusobacterium nucleatum; Cadherins; Cell Proliferation; Mouth Neoplasms; beta Catenin; Carcinoma, Squamous Cell; Humans; Animals; Mice; Cell Line, Tumor; Mice, Nude; Mice, Inbred BALB C; Antigens, CD; Signal Transduction
PubMed: 38698370
DOI: 10.1186/s12903-024-04252-3 -
Fn-OMV potentiates ZBP1-mediated PANoptosis triggered by oncolytic HSV-1 to fuel antitumor immunity.Nature Communications Apr 2024Oncolytic viruses (OVs) show promise as a cancer treatment by selectively replicating in tumor cells and promoting antitumor immunity. However, the current...
Oncolytic viruses (OVs) show promise as a cancer treatment by selectively replicating in tumor cells and promoting antitumor immunity. However, the current immunogenicity induced by OVs for tumor treatment is relatively weak, necessitating a thorough investigation of the mechanisms underlying its induction of antitumor immunity. Here, we show that HSV-1-based OVs (oHSVs) trigger ZBP1-mediated PANoptosis (a unique innate immune inflammatory cell death modality), resulting in augmented antitumor immune effects. Mechanistically, oHSV enhances the expression of interferon-stimulated genes, leading to the accumulation of endogenous Z-RNA and subsequent activation of ZBP1. To further enhance the antitumor potential of oHSV, we conduct a screening and identify Fusobacterium nucleatum outer membrane vesicle (Fn-OMV) that can increase the expression of PANoptosis execution proteins. The combination of Fn-OMV and oHSV demonstrates potent antitumor immunogenicity. Taken together, our study provides a deeper understanding of oHSV-induced antitumor immunity, and demonstrates a promising strategy that combines oHSV with Fn-OMV.
Topics: Herpesvirus 1, Human; Oncolytic Viruses; Animals; Humans; Oncolytic Virotherapy; Mice; RNA-Binding Proteins; Cell Line, Tumor; Fusobacterium nucleatum; Neoplasms; Female; Immunity, Innate; Mice, Inbred BALB C
PubMed: 38693119
DOI: 10.1038/s41467-024-48032-7 -
Journal of Translational Medicine Apr 2024The cancer microbiota was considered the main risk factor for cancer progression. We had proved that Fusobacterium periodonticum (F.p) was higher abundance in Esophageal...
BACKGROUND
The cancer microbiota was considered the main risk factor for cancer progression. We had proved that Fusobacterium periodonticum (F.p) was higher abundance in Esophageal cancer(EC)tissues. Bioinformation analysis found that BCT was a key virulence protein of F.p. However, little is known about the role and mechanism of BCT in EC. This study aimed to recognize the key virulence protein of F.p and explore the mechanism of BCT in promoting EC.
METHODS
We constructed a eukaryotic expression vector and purified the recombinant protein BCT. CCK8 used to analyzed the activity of EC after treated by different concentration of BCT. UPLC-MS/MS and ELISA used to detect the metabonomics and metabolites. The ability of migration and invasion was completed by transwell assay. RT-QPCR, WB used to analyze the expression of relevant genes.
RESULTS
Our data showed that BCT was higher expression in EC tumor tissues (p < 0.05) and BCT in 20 µg/mL promoted the survival, invasion and migration of EC cells (EC109) (p < 0.05). Meanwhile, UPLC-MS/MS results suggested that BCT resulted in an augmentation of hypotaurine metabolism, arachidonic acid metabolism, glycolysis/gluconeogenesis, tryptophan metabolism, citrate cycle activity in EC109. The metabolic changes resulted in decreasing in glucose and pyruvate levels but increase in lactate dehydrogenase (LDH) activity and lactic acid (LA) as well as the expression of glucose transporter 1, Hexokinase 2, LDH which regulated the glycolysis were all changed (p < 0.05). The BCT treatment upregulated the expression of TLR4, Akt, HIF-1α (p < 0.05) which regulated the production of LA. Furthermore, LA stimulation promoted the expression of GPR81, Wnt, and β-catenin (p < 0.05), thereby inducing EMT and metastasis in EC109 cells.
CONCLUSION
Altogether, these findings identified that impact of BCT in regulation of glycolysis in EC109 and its involves the TLR4/Akt/HIF-1α pathway. Meanwhile, glycolysis increasing the release of LA and promote the EMT of EC109 by GPR81/Wnt/β-catenin signaling pathway. In summary, our findings underscore the potential of targeting BCT as an innovative strategy to mitigate the development of EC.
Topics: Humans; Esophageal Neoplasms; Epithelial-Mesenchymal Transition; Lactic Acid; Cell Line, Tumor; Glucose; Cell Movement; Fusobacterium; Bacterial Proteins; Neoplasm Invasiveness; Gene Expression Regulation, Neoplastic
PubMed: 38689341
DOI: 10.1186/s12967-024-05157-z -
World Journal of Gastroenterology Apr 2024Colorectal cancer (CRC) ranks among the most prevalent malignant tumors globally. Recent reports suggest that () contributes to the initiation, progression, and...
BACKGROUND
Colorectal cancer (CRC) ranks among the most prevalent malignant tumors globally. Recent reports suggest that () contributes to the initiation, progression, and prognosis of CRC. Butyrate, a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber, is known to inhibit various cancers. This study is designed to explore whether influences the onset and progression of CRC by impacting the intestinal metabolite butyric acid.
AIM
To investigate the mechanism by which affects CRC occurrence and development.
METHODS
Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of . Additionally, DLD-1 and HCT116 cell lines were exposed to sodium butyrate (NaB) and to examine the effects on proliferative proteins and mitochondrial function.
RESULTS
Our research indicates that the prevalence of in fecal samples from CRC patients is significantly greater than in healthy counterparts, while the prevalence of butyrate-producing bacteria is notably lower. In mice colonized with , the population of butyrate-producing bacteria decreased, resulting in altered levels of butyric acid, a key intestinal metabolite of butyrate. Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells. Consequently, this leads to modulated production of adenosine triphosphate and reactive oxygen species, thereby inhibiting cancer cell proliferation. Additionally, NaB triggers the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, blocks the cell cycle in HCT116 and DLD-1 cells, and curtails the proliferation of CRC cells. The combined presence of and NaB attenuated the effects of the latter. By employing small interfering RNA to suppress AMPK, it was demonstrated that AMPK is essential for NaB's inhibition of CRC cell proliferation.
CONCLUSION
can promote cancer progression through its inhibitory effect on butyric acid, the AMPK signaling pathway.
Topics: Fusobacterium nucleatum; Animals; Colorectal Neoplasms; Gastrointestinal Microbiome; Butyric Acid; Humans; Mice, Inbred BALB C; Mice; Feces; Cell Proliferation; HCT116 Cells; Male; Mitochondria; Fusobacterium Infections; Disease Models, Animal; Cell Line, Tumor; Female; Disease Progression; Dysbiosis; Membrane Potential, Mitochondrial
PubMed: 38681125
DOI: 10.3748/wjg.v30.i14.2018