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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 -
Experimental Dermatology May 2024Hidradenitis Suppurativa (HS) is a chronic autoinflammatory skin disease with activated keratinocytes, tunnel formation and a complex immune infiltrate in tissue. The HS...
Hidradenitis Suppurativa (HS) is a chronic autoinflammatory skin disease with activated keratinocytes, tunnel formation and a complex immune infiltrate in tissue. The HS microbiome is polymicrobial with an abundance of commensal gram-positive facultative (GPs) Staphylococcus species and gram-negative anaerobic (GNA) bacteria like Prevotella, Fusobacterium and Porphyromonas with increasing predominance of GNAs with disease severity. We sought to define the keratinocyte response to bacteria commonly isolated from HS lesions to probe pathogenic relationships between HS and the microbiome. Type strains of Prevotella nigrescens, Prevotella melaninogenica, Prevotella intermedia, Prevotella asaccharolytica, Fusobacterium nucleatum, as well as Staphylococcus aureus and the normal skin commensal Staphylococcus epidermidis were heat-killed and co-incubated with normal human keratinocytes. RNA was collected and analysed using RNAseq and RT-qPCR. The supernatant was collected from cell culture for protein quantification. Transcriptomic profiles between HS clinical samples and stimulated keratinocytes were compared. Co-staining of patient HS frozen sections was used to localize bacteria in lesions. A mouse intradermal injection model was used to investigate early immune recruitment. TLR4 and JAK inhibitors were used to investigate mechanistic avenues of bacterial response inhibition. GNAs, especially F. nucleatum, stimulated vastly higher CXCL8, IL17C, CCL20, IL6, TNF and IL36γ transcription in normal skin keratinocytes than the GPs S. epidermidis and S. aureus. Using RNAseq, we found that F. nucleatum (and Prevotella) strongly induced the IL-17 pathway in keratinocytes and overlapped with transcriptome profiles of HS patient clinical samples. Bacteria were juxtaposed to activated keratinocytes in vivo, and F. nucleatum strongly recruited murine neutrophil and macrophage migration. Both the TLR4 and pan-JAK inhibitors reduced cytokine production. Detailed transcriptomic profiling of healthy skin keratinocytes exposed to GNAs prevalent in HS revealed a potent, extensive inflammatory response vastly stronger than GPs. GNAs stimulated HS-relevant genes, including many genes in the IL-17 response pathway, and were significantly associated with HS tissue transcriptomes. The close association of activated keratinocytes with bacteria in HS lesions and innate infiltration in murine skin cemented GNA pathogenic potential. These novel mechanistic insights could drive future targeted therapies.
Topics: Keratinocytes; Humans; Animals; Mice; Hidradenitis Suppurativa; Staphylococcus aureus; Staphylococcus epidermidis; Fusobacterium nucleatum; Transcriptome; Cytokines; Bacteria, Anaerobic; Interleukin-17; Microbiota; Prevotella
PubMed: 38685821
DOI: 10.1111/exd.15087 -
Surgical Infections May 2024
Topics: Humans; Fusobacterium necrophorum; Cholecystitis, Acute; Fusobacterium Infections
PubMed: 38683633
DOI: 10.1089/sur.2024.061 -
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 -
Journal of Dentistry Jul 2024This study aimed to identify the oral microbiota factors contributing to low birth weight (LBW) in Chinese pregnant women and develop a prediction model using machine...
OBJECTIVES
This study aimed to identify the oral microbiota factors contributing to low birth weight (LBW) in Chinese pregnant women and develop a prediction model using machine learning.
METHODS
A nested case-control study was conducted in a prospective cohort of 580 Chinese pregnant women, with 23 LBW cases and 23 healthy delivery controls matched for age and smoking habit. Saliva samples were collected at early and late pregnancy, and microbiome profiles were analyzed through 16S rRNA gene sequencing.
RESULTS
The relative abundance of Streptococcus was over-represented (median 0.259 vs. 0.116) and Saccharibacteria_TM7 was under-represented (median 0.033 vs. 0.068) in the LBW case group than in controls (p < 0.001, p = 0.015 respectively). Ten species were identified as microbiome biomarkers of LBW by LEfSe analysis, which included 7 species within the genus of Streptococcus or as part of 'nutritionally variant streptococci' (NVS), 2 species of opportunistic pathogen Leptotrichia buccalis and Gemella sanguinis (all LDA score>3.5) as risk biomarkers, and one species of Saccharibacteria TM7 as a beneficial biomarker (LDA= -4.5). The machine-learning model based on these 10 distinguished oral microbiota species could predict LBW, with an accuracy of 82 %, sensitivity of 91 %, and specificity of 73 % (AUC-ROC score 0.89, 95 % CI: 0.75-1.0). Results of α-diversity showed that mothers who delivered LBW infants had less stable salivary microbiota construction throughout pregnancy than the control group (measured by Shannon, p = 0.048; and Pielou's, p = 0.021), however the microbiome diversity did not improve the prediction accuracy of LBW.
CONCLUSIONS
A machine-learning oral microbiome model shows promise in predicting low-birth-weight delivery. Even in cases where oral health is not significantly compromised, opportunistic pathogens or rarer taxa associated with adverse pregnancy outcomes can still be identified in the oral cavity.
CLINICAL SIGNIFICANCE
This study highlights the potential complexity of the relationship between oral microbiome and pregnancy outcomes, indicating that mechanisms underlying the association between oral microbiota and adverse pregnancy outcomes may involve complex interactions between host factors, microbiota, and systemic conditions. Using machine learning to develop a predictive model based on specific oral microbiota biomarkers provides a potential for personalized medicine approaches. Future prediction models should incorporate clinical metadata to be clinically useful for improving maternal and child health.
Topics: Humans; Female; Pregnancy; Case-Control Studies; Infant, Low Birth Weight; Microbiota; Infant, Newborn; Adult; Saliva; Mouth; Prospective Studies; Machine Learning; RNA, Ribosomal, 16S; Streptococcus; Biomarkers; China; Leptotrichia; Risk Factors
PubMed: 38679133
DOI: 10.1016/j.jdent.2024.105018 -
International Journal of Molecular... Apr 2024Complex microbial communities have been reported to be involved in endodontic infections. The microorganisms invade the dental pulp leading to pulpitis and initiating...
Complex microbial communities have been reported to be involved in endodontic infections. The microorganisms invade the dental pulp leading to pulpitis and initiating pulp inflammation. is a dominant bacterium implicated in both primary and secondary endodontic infections. Drugs targeting the molecular machinery of will minimize pulp infection. LpxA and LpxD are early acyltransferases involved in the formation of lipid A, a major component of bacterial membranes. The identification of leads which exhibit preference towards successive enzymes in a single pathway can also prevent the development of bacterial resistance. A stringent screening strategy utilizing physicochemical and pharmacokinetic parameters along with a virtual screening approach identified two compounds, Lomefloxacin and Enoxacin, with good binding affinity towards the early acyltransferases LpxA and LpxD. Lomefloxacin and Enoxacin, members of the fluoroquinolone antibiotic class, exhibit wide-ranging activity against diverse bacterial strains. Nevertheless, their effectiveness in the context of endodontic treatment requires further investigation. This study explored the potential of Lomefloxacin and Enoxacin to manage endodontic infections via computational analysis. Moreover, the compounds identified herein serve as a foundation for devising novel combinatorial libraries with enhanced efficacy for endodontic therapeutic strategies.
Topics: Fusobacterium nucleatum; Humans; Anti-Bacterial Agents; Lipopolysaccharides; Molecular Docking Simulation; Computer Simulation; Fusobacterium Infections; Enoxacin; Bacterial Proteins; Pulpitis
PubMed: 38673822
DOI: 10.3390/ijms25084239 -
Journal of Personalized Medicine Mar 2024Patients with COVID-19 infection have distinct oropharyngeal microbiota composition and diversity metrics according to disease severity. However, these findings are not...
Patients with COVID-19 infection have distinct oropharyngeal microbiota composition and diversity metrics according to disease severity. However, these findings are not consistent across the literature. We conducted a multicenter, prospective study in patients with COVID-19 requiring outpatient versus inpatient management to explore the microbial abundance of taxa at the phylum, family, genus, and species level, and we utilized alpha and beta diversity indices to further describe our findings. We collected oropharyngeal washing specimens at the time of study entry, which coincided with the COVID-19 diagnosis, to conduct all analyses. We included 43 patients in the study, of whom 16 were managed as outpatients and 27 required hospitalization. , , , , , and were the most abundant phyla among patients, while 61 different families were detected, of which the and families were the most predominant. A total of 132 microbial genera were detected, with being the predominant genus in outpatients, in contrast to hospitalized patients, in whom the genus was predominant. LeFSe analysis identified 57 microbial species in the oropharyngeal washings of study participants that could discriminate the severity of symptoms of COVID-19 infections. Alpha diversity analysis did not reveal a difference in the abundance of bacterial species between the groups, but beta diversity analysis established distinct microbial communities between inpatients and outpatients. Our study provides information on the complex association between the oropharyngeal microbiota and SARS-CoV-2 infection. Although our study cannot establish causation, knowledge of specific taxonomic changes with increasing SARS-CoV-2 infection severity can provide us with novel clues for the prognostic classification of COVID-19 patients.
PubMed: 38672996
DOI: 10.3390/jpm14040369