Attenuating the pathological cycle of periodontitis: CGL NPs suppress pathological mineralization and modulate the periodontal microenvironment.

Impact of saliva on the efficacy of antiseptics against selected periopathogens.

Colorectal cancer (CRC) is caused by a complex interaction between genetic, environmental, and microbial risk factors, and intestinal microbiota has critical roles in inflammation, immunology, and epithelial integrity. Pathobionts from the intestines (Fusobacterium nucleatum, Bacteroides fragilis, and E. coli that produce colibactin) promote DNA damage, immunity protection from cancer therapy, and resistance to chemotherapy treatments. The beneficial commensals and metabolites of intestinal microbes (namely butyrate) increase the mucosal immune response and inhibit tumor-specific signaling mechanisms. Microbe controlled changes of populations of myeloid, lymphoid, and regulatory cells dictate the state of the tumor-immune system and provide actionable checkpoints and biomarkers for cancer therapy. An enormous variety of clinical interventions based on the gut microbiota (probiotics, prebiotics, and fecal microbiota transfer) and diagnostic approaches is currently being developed. Translational issues are difficult due to the interindividual variability and regulatory complexity of tumors. Research needs include standardizing multi-omics data from multidisciplinary teams and mechanistic validation in organoid and gnotobiotic models as well as prediction algorithms to optimize the microbiome-based medicine for individual patients. Targeting the immune-microbiota axis may provide new therapeutic strategies in the diagnosis, prognosis, and therapy of CRC.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, with outcomes critically dependent on timely diagnosis, accurate risk stratification, and individualized treatment. Traditional markers such as CEA, KRAS/NRAS, BRAF, and MSI status, while foundational, are insufficient to address the full complexity of CRC biology. Over the past decade, a new generation of biomarkers has emerged spanning liquid biopsy, stool-based methylation, genomics, epigenomics, immune profiling, microbiome analysis, radiomics, patient-derived organoids, and multiomics integration-collectively redefining how CRC is detected, classified, and treated. This narrative review synthesizes evidence from 73 human studies published between 2010 and 2024, identified through structured searches of PubMed, Embase, Web of Science, and the Cochrane Library, and quality-assessed using QUADAS-2 and Newcastle-Ottawa tools. Circulating tumor DNA (ctDNA) emerged as the most clinically validated biomarker, demonstrating superior performance in minimal residual disease (MRD) detection, recurrence prediction, and real-time therapy monitoring. Stool DNA methylation assays showed strong sensitivity for early CRC and advanced adenoma detection. Genomic markers including BRAF V600E, POLE/POLD1, HER2, and KRAS G12C now directly inform targeted therapy selection, while immune biomarkers-MSI-H, TMB, and Immunoscore-guide immunotherapy decisions and stratify prognosis beyond TNM staging. Microbiome signatures, particularly Fusobacterium nucleatum and colibactin-producing Escherichia coli, were associated with chemo resistance and tumor progression. Radiomics and AI-driven imaging models provided noninvasive assessment of nodal involvement and neo-adjuvant therapy response. Patient-derived organoids demonstrated capacity to predict individual drug sensitivity, and multiomic integration enabled refined molecular subtyping. Despite this progress, widespread clinical adoption remains limited by assay variability, lack of prospective multicenter validation, and implementation barriers including cost and infrastructure. As these technologies mature, their integration into standardized, multidisciplinary workflows will be essential to translating biomarker innovation into improved patient outcomes across all stages of CRC care.

Adult periodontitis is a chronic inflammatory disease characterized by microbial dysbiosis and host-microbe imbalance in the oral cavity. In this study, the composition and antibiotic susceptibility of the salivary microbiota in adults with mild periodontitis were analyzed to emphasize the influence of lifestyle factors on microbial ecology and resistance trends. Saliva samples collected from clinically diagnosed individuals were analyzed using selective culture-based methods and the Kirby-Bauer disc diffusion assay. Statistical analyses were performed to evaluate interspecies growth variability and antimicrobial responses. It revealed distinct salivary microbial profiles in patients with periodontitis compared to those of healthy individuals. Fusobacterium nucleatum exhibited the highest optical density, indicating increased proliferation and potential involvement in disease progression. Lifestyle variables, particularly smoking and dietary habits, significantly influenced microbial composition (r = 0.73 for smoking; r = 0.59 for tobacco use). Antibiotic susceptibility testing has revealed substantial interspecies variation, with ciprofloxacin and tetracycline showing the highest inhibitory efficacy, whereas azithromycin and clindamycin were largely ineffective. Moderate positive correlations between Prevotella, Clostridium, and F. nucleatum (r = 0.61-0.65) suggest possible shared resistance mechanisms or ecological adaptation. Overall, combined effects of behavioral and microbial factors can shape early periodontal dysbiosis and antibiotic resistance.

The development of safe, efficient, and convenient strategies for teeth whitening and oral hygiene remains a significant challenge in modern dentistry. In this work, we report a multifunctional composite hydrogel (CBA) that enables simultaneous teeth whitening and antibacterial activity through the synergistic coupling of localized surface plasmon resonance (LSPR) and piezo-phototropic effects. The CBA hydrogel, comprising BaTiO3 nanocubes decorated with Au nanoparticles and embedded in a biocompatible calcium alginate hydrogel matrix, can efficiently generate reactive oxygen species (ROS) under combined light and ultrasound stimulation. This dual activation greatly enhances pigment degradation on enamel surfaces and effectively inactivates pathogenic bacteria such as Fusobacterium nucleatum. Compared with the control group, the hydrogel exhibits three orders of magnitude reduction in bacteria inactivation and a six-fold increase in whitening efficiency, while maintaining excellent enamel integrity. Photoelectrochemical and photoluminescence analyses reveal that the synergistic interaction among the LSPR-induced hot electrons, piezoelectric polarization field, and semiconductor band modulation significantly improves charge separation and ROS generation efficiency. This work not only provides fundamental insights into the cooperative mechanism of LSPR and piezo-phototronic effects but also establishes a practical and safe approach for next-generation dental care materials.

Abstract Fusobacterium nucleatum ( F . nucleatum ), recognized for its opportunistic pathogenicity, is a prevalent pathogen implicated in several diseases. Emerging evidence highlights the crucial role of F . nucleatum –derived extracellular vesicles ( F . nucleatum EVs) in mediating virulence and serving as carriers of diverse bioactive components that facilitate host–pathogen interactions. F . nucleatum EVs can disseminate from the oral cavity to the gastrointestinal tract and joints, promoting the onset and progression of oral inflammatory diseases, head and neck squamous cell carcinoma, rheumatoid arthritis, inflammatory bowel disease, and colorectal cancer through various signaling pathways. A deeper understanding of F . nucleatum EVs will advance the understanding of the pathogenesis of related diseases and inform the development of effective infection control strategies. This review systematically summarizes recent progress in the biogenesis, molecular composition, and pathogenic roles of F . nucleatum EVs across various disease contexts and evaluates potential strategies for the diagnosis, treatment, and management of conditions involving F . nucleatum and its EVs.

Fusobacterium nucleatum contributes to the progression of colorectal cancer (CRC). Nicotinamide (NAM), a safe, cost-effective, and water-soluble form of vitamin B3, has been shown to inhibit the virulence of various microorganisms. However, its effect on F. nucleatum pathogenicity remains unclear. In this study, we evaluated the effects of NAM on the pathogenic traits of F. nucleatum. A quarter of the minimum inhibitory concentration of NAM (~50 mM) was found to simultaneously inhibit bacterial growth, biofilm formation, and the adhesion and invasion of CRC cells. Transcriptomic analysis of F. nucleatum treated at this concentration revealed that 257 genes were upregulated and 316 genes were downregulated. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology functional enrichment analyses indicated that these differentially expressed genes are involved in multiple pathways, including oxidative phosphorylation, biofilm formation, two-component systems, ATP synthesis, and other processes. Furthermore, we showed that NAM, as a class III histone deacetylase inhibitor, could inhibit the deacetylase activity of CobB, thereby increasing the acetylation level of the FomA and reducing its binding ability to CRC cells. In summary, these findings suggest that NAM can attenuate multiple virulence traits of F. nucleatum and may serve as a promising F. nucleatum-targeted strategy for prevention and treatment of CRC.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths, accounting for more than 900,000 deaths a year worldwide. Microbial dysbiosis, including the presence of oral bacteria in the gut, has been linked to CRC. Some mechanisms by which specific microorganisms potentially drive tumorigenesis have been described, but there is a lack of studies elucidating whole microbiota activity in the tumor and their implication for the development of the disease. Here, the metatranscriptomic data of tumor and control tissue-associated microbiota (n = 18 pairs), as well as from subgingival sulcus (n = 15) of CRC patients, was analyzed. We confirmed that Fusobacterium nucleatum was more active in the tumor tissue than in the control gut mucosa. In addition, the activity of this species was positively correlated with other oral bacteria in the tumors, including Parvimonas micra, Peptostreptococcus stomatis, and Granulicatella adiacens, along with gut bacteria like Hungatella hathewayi, suggesting a potential relationship among them. Regarding bacterial gene expression, a change in the functional profile was observed, including a higher expression of genes associated with carbon metabolism in control in contrast to an increase of amino acid-related genes in tumor. Furthermore, genes implicated in the biosynthesis and transport of lipopolysaccharide were increased in tumors. Interestingly, a significantly higher expression in tumor than control tissue of potential virulence factors from F. nucleatum was found, supporting their relevance in niche colonization and tumorigenesis. Correlation analysis of the bacterial activity with the host transcriptional profile showed significant correlations of the Fusobacterium-Peptostreptotoccus-Hungatella cluster with human genes involved in inflammation and metastasis, confirming the association of this microbial consortium with tumor development. For the first time, the gene expression profiles of oral bacteria in the gut and the oral cavity were compared. The cluster of co-active bacteria identified in tumors was partially found in the oral samples, suggesting a stable interaction and potential synergy. Although there were thousands of differentially expressed genes between subgingival sulcus and tumor tissue, the expression of key virulence factors was not significantly different. In short, this study discovered new traits about tumor microbial-associated composition and activity and its connection with the oral composition that would be essential to unravel the translocation, colonization, and tumorigenesis of the CRC.

A cross-kingdom alliance driving colorectal cancer.

Immune checkpoint blockade transforms outcomes for the 15% of colorectal cancers (CRCs) with mismatch-repair deficiency; yet most tumours remain refractory. Beneficial gut microbes can change this. Akkermansia muciniphila, Bacteroides fragilis, and short-chain fatty acid producers prime dendritic cells to produce interleukin (IL)-12, polarise Th1 cells, and reinvigorate CD8+ T-cells. Antibiotics, Western-style diets, and Fusobacterium nucleatum foster myeloid suppression and β-catenin- or IL-17-mediated signalling, which blunt checkpoint activity. Multi-omics analyses link biosynthetic genes for inosine, riboflavin, and folate to durable clinical benefit. Faecal microbiota transplantation from responders has produced objective regressions in otherwise refractory microsatellite-stable disease. This narrative review maps CRC-microbiota-immune crosstalk, evaluates biomarkers and interventions, and proposes a CRC-specific, three-tiered clinical algorithm. We outline standards for trial design and manufacturing processes to facilitate the translation of microbiota-guided therapy into routine practice.

This study evaluated the effects of dried nettle (Urtica dioica) supplementation on broiler ducks. A total of 180 Cherry Valley ducks were assigned to three groups: control, 1% nettle, and 3% nettle. Growth performance, carcass traits, meat quality, intestinal morphology, digesta viscosity, liver gene expression, and cecal microbiota were assessed. During rearing, the ducks' body weight, growth, feed intake, and conversion ratio were controlled and calculated. After slaughter, carcass composition, meat quality, duodenum and jejunum morphology, liver gene expression, and intestinal microbiota composition were analyzed. Nettle supplementation did not influence body weight, feed intake, feed conversion ratio, European Broiler Index, carcass yield, organ weights, or meat quality parameters. However, notable improvements in intestinal structure were observed, especially in ducks receiving 3% nettle, which showed increased duodenal villus width and surface area, as well as higher jejunal villus height. Digesta viscosity was significantly reduced in the jejunum of the 3% nettle group. Gene expression analysis revealed significant upregulation of CYP7A1 in the 1% nettle group and ALB in the 3% group. Antioxidant-related genes (SOD1 and SOD2) were significantly upregulated, and GPX2 downregulated, only in the 3% nettle group, with no significant changes observed in the 1% group. Although beneficial bacterial populations were unchanged, a marked reduction in Fusobacterium nucleatum was detected in the 3% group, indicating a selective antimicrobial effect. Dried nettle at 3% improved gut morphology and antioxidant responses without affecting growth or meat quality, supporting its potential as a functional feed additive.

To determine the effect of probiotic lozenges containing Lacticaseibacillus rhamnosus PB01, Latilactobacillus curvatus EB10 and xylitol after non-surgical periodontal treatment (NSPT) on changes in microbial composition. The secondary aims were to assess the clinical and immunological impact of probiotic consumption. Eighty adults with stage II or III periodontitis were enrolled and received NSPT at baseline, followed by a 12-week consumption of probiotics or placebo. Microbial sampling and clinical examination were performed at baseline, Week 6 and Week 12. The subgingival microbiota was analysed using 16S sequencing, the salivary microbiota by metagenomic sequencing and selected cytokines and proteases in saliva by bead-based immunoassay. Sixty-one participants completed the trial (probiotics n = 32, placebo n = 29). At Week 12, Treponema socranskii, Selenomonas sputigena, Dialister pneumosintes, Dialister invisus, Anaeroglobus geminatus and Fusobacterium nucleatum were significantly associated with the placebo group, while Streptococcus sanguinis, Neisseria elongata and Neisseria oralis were associated with the probiotic group. Bleeding on probing percentage (BoP%) and number of periodontal pockets (PPD) ≥ 5 mm decreased significantly more in the probiotic group compared to the placebo group (p < 0.05). The tested probiotic supplement resulted in an additional short-term decrease in periodontitis-associated species along with greater improvements in BoP% and PPD ≥ 5 mm 12 weeks post-NSPT, compared to the placebo group.

To evaluate the clinical utility of robot-assisted incision and drainage in the management of a polymicrobial brain abscess located in the central region. We retrospectively analyzed a case of polymicrobial odontogenic brain abscess in a 71-year-old male who presented with stroke-like symptoms. The patient was admitted due to progressive right-sided weakness, initially mimicking an acute ischemic stroke. Gadolinium-enhanced T1-weighted magnetic resonance imaging (MRI) revealed ring-enhancing lesions in the left precentral gyrus and the right temporal lobe, with corresponding high signal on diffusion-weighted imaging (DWI), highly suggestive of a brain abscess. Following empirical antibiotic therapy (vancomycin and meropenem), the patient clinically deteriorated, and a repeat MRI demonstrated enlargement of the left central abscess. During the Remebot robotic navigation, the abscess was incised and drained, yielding thick, yellowish-white purulent material. Postoperative metagenomic next-generation sequencing (mNGS) of the pus identified a polymicrobial infection comprising Fusobacterium nucleatum, Streptococcus constellatus, Parvimonas micra, and Porphyromonas gingivalis. Based on the microbiological findings, the antibiotic regimen was tailored to a triple combination of vancomycin, meropenem, and metronidazole for 2 weeks, followed by vancomycin plus meropenem for an additional 4 weeks, complemented by rehabilitation and hyperbaric oxygen therapy. The patient demonstrated remarkable neurological recovery. One month post-surgery, right limb muscle strength had returned to grade 5, with only mild residual impairment in fine-motor coordination of the right hand. Three-month follow-up MRI revealed complete resolution of the previously observed intracranial ring-enhancing lesions. For eloquent-area brain abscesses that progress despite medical management, robot-assisted incision and drainage offers a safe, precise, and efficacious minimally invasive surgical option. Integration of mNGS technology for pathogen identification enables targeted antimicrobial therapy, a pivotal step toward achieving favorable outcomes in complex infections.

Oral dysbiosis can accelerate the progression of head and neck squamous cell carcinoma (HNSCC) by fostering a pro-inflammatory, immunosuppressive, and metabolically altered environment. This narrative review examines the relationships between periodontitis-associated bacteria and HNSCC, focusing on their impact on oncogenic pathways, immune modulation, and epigenetic alterations. A comprehensive search of PubMed and Google Scholar was conducted up to January 28, 2026, without time limitations, using all relevant keywords related to HNSCC, head and neck cancers, periodontitis, and the oral microbiome. Key periodontitis-associated bacteria, including Fusobacterium nucleatum, Porphyromonas gingivalis, Capnocytophaga gingivalis, and Prevotella intermedia, may play a vital role in HNSCC. These bacteria stimulate several oncogenic pathways, including Wnt/β-catenin, NF-κB, and PI3K/Akt, enabling HNSCC to evade immune responses, trigger epithelial-to-mesenchymal transition and angiogenesis, and encourage cell proliferation and stemness. Furthermore, microbial interactions within the tumor microenvironment significantly impact treatment resistance, particularly in the context of immune checkpoint inhibitor therapy. Incorporating periodontal screening, microbiome profiling, and bacterial-targeted therapies into oncology could enhance treatment outcomes for HNSCC. Future research should investigate CRISPR-based microbial interventions, targeted epigenetic therapies, and microbiome-driven precision oncology strategies.

Colorectal cancer (CRC) is a complex malignancy driven by genetic, environmental, and lifestyle factors. A critical contributor to CRC tumor initiation and progression is gut microbial dysbiosis. Fusobacterium nucleatum, an oral commensal bacterium, is a potent promoter of malignancy rather than a passive colonizer. This review examines the molecular mechanisms by which F. nucleatum promotes CRC progression, focusing on one indirect systemic and three direct local mechanisms. First, the lipopolysaccharide-Toll-like receptor 4 axis sustains a chronic inflammatory loop that remodels the tumor microenvironment. Second, the fibroblast activation protein 2-T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain interaction facilitates immune evasion by suppressing T cell and natural killer cell cytotoxic activity. Third, the Fusobacterium adhesin A-E-cadherin/Wnt pathway acts as a potent "second hit," amplifying β-catenin signaling and driving proliferation in cells with pre-existing mutations in adenomatous polyposis coli. Beyond these local effects, this review highlights a novel indirect mechanism involving the gut-kidney axis. Specifically, F. nucleatum is hypothesized to contribute to systemic levels of indoxyl sulfate, a uremic toxin that reinforces a systemic feedback loop via pro-proliferative signaling. These synergistic mechanisms collectively remodel the tumor microenvironment by promoting immune suppression, chronic inflammation, and metabolic reprogramming. Within this framework, F. nucleatum collaborates with genetic lesions to accelerate disease progression. This framework provides a crucial foundation for developing innovative diagnostics and microbe-targeted therapies-such as phage therapy and vaccines-to substantially improve the prognosis of patients with CRC.

Candida-bacteria interactions in peri-implantitis: A narrative review of evidence, mechanisms, and clinical implications.

Circular RNAs (circRNAs) perform critical functions in cancer biology, commonly serving as microRNA (miRNA) sponges to modulate gene expression. Nevertheless, their participation in gut microbiota-driven colorectal cancer (CRC) has yet to be substantially investigated. Fusobacterium nucleatum (F. nucleatum), a well-recognized oncogenic bacterium in the human gut, has been implicated in CRC development, but the underlying mechanisms are not fully defined. In this study, we identified a novel circRNA, circPTBP3, which is the most significantly upregulated circRNA upon F. nucleatum infection, and is significantly upregulated in CRC tissues. CircPTBP3 is preferentially transcribed over its host gene PTBP3 in response to F. nucleatum through activation of the transcription factor ETS1. Functional assays demonstrated that circPTBP3 enhances CRC cell proliferation and tumor growth in vitro and in vivo. Mechanistically, circPTBP3 acts as a molecular sponge for miR-760, thereby relieving its suppression of the downstream target gene PUM1. In clinical CRC specimens, circPTBP3 expression showed a positive correlation with F. nucleatum abundance, PUM1 expression, larger tumor sizes, advanced TNM stages, and a negative correlation with miR-760 levels. These findings establish for the first time that circPTBP3 functions as a pivotal mediator of F. nucleatum 's oncogenicity, and reveal a novel F. nucleatum-circPTBP3-miR-760-PUM1 regulatory axis that promotes CRC progression. CircPTBP3 may serve as a potential biomarker and therapeutic target in F. nucleatum-associated colorectal carcinogenesis.

Fusobacterium nucleatum, a gram-negative bacterium implicated in periodontal disease, contributes to tumor progression in various cancers. Whether the presence of F. nucleatum inhibits tumor progression of some cancers is largely unknown. Here, we identify an interaction between F. nucleatum and the natural killer (NK) cell receptor NKp46. Analysis of TCGA datasets revealed that the co-occurrence of F. nucleatum and high NKp46 expression correlates with improved survival in head and neck cancers but not in colorectal cancers. Using binding assays, we demonstrate that both human NKp46 and its murine ortholog, Ncr1, directly recognize the fusobacterial adhesin RadD. Genetic deletion of radD or blockade of NKp46 significantly impaired NK cell-mediated cytotoxicity in vitro and promoted tumor-cell growth. In vivo, infection with F. nucleatum accelerated tumor progression, with an exacerbated effect observed in the absence of RadD or NKp46. These findings highlight RadD as a critical ligand for NKp46 and establish the NKp46-RadD axis as a key interface in host-microbe-tumor interactions, offering a novel target for immunotherapeutic intervention in cancer influenced by microbial factors.

A novel antimicrobial peptide AH-12 attenuates mitochondrial response to inflammatory stimuli and prevents periodontitis via antibacterial and anti-inflammatory effects.