Breast cancer (BC) is one of the leading causes of death and morbidity among women worldwide. Epidemiologic evidence shows that the risk of BC and other chronic diseases decreases as the proportion of whole plant foods increases, while the proportion of animal foods (fish, meat, poultry, eggs, seafood, and dairy products) and non-whole plant foods (e.g., refined grains, added sugars, French fries) in the diet decreases. Whole plant foods include fruits, vegetables, roots, tubers, whole grains, legumes, nuts, and seeds from which no edible part has been removed and to which no non-whole food been added. A whole plant foods diet lowers insulin resistance, inflammation, excess body fat, cholesterol, and insulin-like growth factor 1 and sex hormone bioavailability; it also increases estrogen excretion, induces favorable changes in the gut microbiota, and may also favorably affect mammary microbiota composition and decrease the risk of early menarche, all contributing to reduced BC incidence, recurrence, and mortality. This review explores the connection between a whole plant foods diet and BC risk and mortality as well as the potential mechanisms involved. Additionally, this diet is compared with other dietary approaches recommended for BC. A whole plant foods diet seems the optimal dietary pattern for BC and overall disease prevention as it exclusively consists of whole plant foods which, based on existing evidence, lead to the best health outcomes.

Pancreatic cancers have high mortality and rising incidence rates which may be related to unhealthy western-type dietary and lifestyle patterns as well as increasing body weights and obesity rates. Recent data also suggest a role for the gut microbiome in the development of pancreatic cancer. Here, we review the experimental and observational evidence for the roles of the oral, gut and intratumoural microbiomes, impaired gut barrier function and exposure to inflammatory compounds as well as metabolic dysfunction as contributors to pancreatic disease with a focus on pancreatic ductal adenocarcinoma (PDAC) initiation and progression. We also highlight some emerging gut microbiome editing techniques currently being investigated in the context of pancreatic disease. Notably, while the gut microbiome is significantly altered in PDAC and its precursor diseases, its utility as a diagnostic and prognostic tool is hindered by a lack of reproducibility and the potential for reverse causality in case-control cohorts. Future research should emphasise longitudinal and mechanistic studies as well as integrating lifestyle exposure and multi-omics data to unravel complex host-microbiome interactions. This will allow for deeper aetiologic and mechanistic insights that can inform treatments and guide public health recommendations.

Fusobacterium nucleatum (Fn) enrichment has been identified in colorectal cancer and its liver metastases. In this study, we found that Fn predominantly accumulated within colorectal cancer cells, correlating with colorectal cancer liver metastasis. Clinically, the administration of high doses of antibiotics and chemotherapeutic agents can disrupt the balance of the host microbiota. To address this clinical challenge, metronidazole (MTI) and oxaliplatin (OXA) are encapsulated within poly (lactic-co-glycolic acid) (PLGA) nanoparticles. Neutrophil membrane vesicles are extracted from murine bone marrow and coated with these nanoparticles (NM@PLGA-MTI-OXA), creating neutrophil-mimetic nanoparticles with dual targeting capabilities for antibacterial and anticancer purposes. The neutrophil membrane coating, compared with free drugs, is found to enhance nanoparticle uptake by tumor cells, facilitating intracellular bacterial elimination and tumor cell death. Further experiments reveal that NM@PLGA-MTI-OXA reverses the Fn-induced epithelial-mesenchymal transition (EMT) in tumor cells during metastasis and remodels the immunosuppressive microenvironment, suppressing colorectal cancer and liver metastasis development while minimizing broad-spectrum damage to the commensal microbiota.

The gut microbiota is intricately associated with the onset and progression of colorectal cancer (CRC), leading to significant interest in developing prevention and treatment strategies that leverage gut microbiota. In this study, we collected 57 samples from 19 CRC patients, comprising cancerous tissue, paracancerous tissue, and normal mucosa. Utilizing metagenomic sequencing and bioinformatics analysis, we identified differences in the microbiomes and their functional characteristics across the various tissue types. The results indicated that species such as Alistipes putredinis were predominantly found in normal tissues, while Pseudomonas putida was enriched in paracancerous tissue, and Malassezia restricta was prevalent in cancerous tissues. Furthermore, the microbial functions exhibited variability among the different tissue types. Random forest analysis suggested that Moraxella osloensis may be implicated in the onset and progression of colorectal cancer. We also classified the patients into three subgroups based on the anatomical location of the colorectum: right-sided colon, left-sided colon, and rectum. The subgroup analysis revealed that the microbiota enriched in normal mucosa and paracancerous tissue varied across different anatomical sites. These findings not only elucidate the characteristics of the microbiomes in the normal mucosa, paracancerous tissue, and cancerous tissues of CRC patients, thereby providing new potential targets for clinical diagnosis and treatment, but also contribute to the existing microbiome data pertinent to CRC research.IMPORTANCEThis study provides crucial insights into the relationship between gut microbiota and colorectal cancer (CRC) by analyzing microbial communities in different tissue types and anatomical locations of CRC patients. We identified distinct microbial signatures, such as Alistipes putredinis in normal tissues and Malassezia restricta in cancerous tissues, indicating location-specific microbiomes with unique functional attributes. These findings suggest potential new biomarkers or therapeutic targets for CRC. The observed microbiota variations among right-sided colon, left-sided colon, and rectum cancers underscore the heterogeneity of CRC, pointing toward more personalized treatment strategies. By enhancing our understanding of the microbiome's role in CRC, this research paves the way for innovative diagnostic tools and targeted therapies tailored to individual patient profiles. This work is essential for advancing clinical approaches to CRC management.

Strict and facultative anaerobic bacteria are widely associated with both acute and chronic airway diseases. However, their potential role(s) in disease pathophysiology remains poorly understood due to inherent limitations of existing laboratory models and conflicting oxygen demands between anaerobes and host cells. To address these limitations, here, we describe a dual oxic-anoxic culture (DOAC) approach that maintains an oxygen-limited microenvironment at the apical epithelial interface while host cells are oxygenated basolaterally. This platform enables epithelial-anaerobe co-culture for ~48 h, and we demonstrate its utility by evaluating reciprocal interactions between the oxygen-sensitive anaerobic bacterium, Fusobacterium nucleatum, and oxygen-demanding airway epithelial cells at the transcriptional level. Using bulk RNAseq, we demonstrate that epithelial colonization results in altered gene expression by F. nucleatum, highlighted by the differential expression of genes associated with virulence, ethanolamine and lysine metabolism, metal uptake, and other transport processes. We also combine DOAC with single-cell RNA sequencing to reveal a cell type-specific transcriptional response of the airway epithelium to F. nucleatum infection, including the increased expression of inflammatory marker genes and cancer-associated pathways. Together, these data illustrate the versatility of DOAC while revealing new insights into anaerobe-host interactions and their mechanistic contributions to airway disease pathophysiology.IMPORTANCEConflicting oxygen demands between anaerobes and host cells present a significant barrier to in vitro modeling of how these cell types interact. To this end, the significance of our dual oxic-anoxic culture (DOAC) approach lies in its ability to maintain anaerobe and epithelial viability during co-culture, paving the way for new insights into the role(s) of anaerobic microbiota in disease. We use DOAC to interrogate reciprocal interactions between the airway epithelium and Fusobacterium nucleatum-an anaerobic commensal with pathogenic potential. Given its link to a range of diseases, from localized infections to various cancers, these data showing how F. nucleatum bacterium re-shapes its metabolism and virulence upon epithelial colonization provide new mechanistic insight into F. nucleatum physiology and how the host responds. We use F. nucleatum as our model, but the DOAC platform motivates additional studies of the gut, lung, and oral cavity, where host-anaerobe interactions and the underlying mechanisms of pathogenesis are poorly understood.

Understanding the complex interplay between intestinal microbiomes and ampullary tumors is crucial for distinguishing between adenomas and carcinomas, especially when considering the role of Fusobacterium. We characterized the microbiome associated with ampullary tumors using samples collected from the tumor surface (tumor samples, TSs) and surrounding normal duodenal mucosa (normal samples, NSs) via brush rubbing. In total, samples from 17 patients, divided into an adenoma group (n = 11) and a carcinoma group (n = 6), were analyzed. The Shannon α-diversity index was significantly higher in the carcinoma group compared with the adenoma group, indicating a more diverse bacterial community in the carcinoma environment. The TSs of the carcinoma group exhibited enrichment of Fusobacterium, Leptotrichia, Methylorubrum, and Micrococcus. The relative abundance of Fusobacterium increased as the tumor progressed. The NSs of the carcinoma group showed a higher presence of Fusobacterium, Porphyromonas, Granulicatella, Rikenellaceae RC9 gut group, and Solobacterium, whereas Bergeyella was more prevalent in the adenoma group. These results suggest that ampullary carcinomas exhibit a characteristic microbiome compared to adenomas. Fusobacterium is enriched in the tumor and surrounding normal duodenal mucosa, increases in abundance as the tumor progresses, and may be associated with ampullary tumors.

Studies have shown that patients with periodontitis (PD) have an increased risk of breast cancer (BC). However, the exact mechanism remains to be further investigated. This study aimed to investigate the genes, pathways and immune cells that may interact with PD and BC. From the Gene Expression Omnibus (GEO) and TCGA databases, we retrieved the gene expression profiles of samples with PD and BC, respectively. Common genes between two diseases were found using differential expression analysis and weighted gene co-expression network analysis (WGCNA). Machine learning methods were used to find shared diagnostic genes. Single-sample GSEA (ssGSEA) was performed to study the expression profiles of 28 immune cells in PD and BC, and single-cell RNA sequencing (scRNA-seq) data was used to visualize localization of shared genes. Finally, we employed qRT-PCR and immunohistochemistry staining to confirm the expression of hub genes in two diseases. PD and BC had 21 shared crosstalk genes, which were primarily related to peptide hormone response, organic acid transmembrane transport, and carboxylic acid transmembrane transport. By using machine learning methods, ANKRD29 and TDO2 were the most efficient shared diagnostic biomarkers, which were confirmed by Immunohistochemical staining and qRT-PCR. ssGSEA showed that immunology was involved in both diseases and that ANKRD29 and TDO2 may be involved in both diseases by mediating immune cells. scRNA-seq further confirms the importance of these genes in regulating immunity in both diseases. In brief, our study identified 2 genes that may serve as biomarkers and targets for the diagnosis and treatment of PD and BC.

Familial aggregation is common in nasopharyngeal carcinoma (NPC), yet the impact of oral microbiome dysbiosis on this occurrence remains largely unexplored. We recruit 127 families (649 members, 1-5 patients each) and a case-control cohort of 337 individuals, validating findings in an additional cohort of 995 individuals. Significant microbial similarity is observed among family members, with family factors contributing most to microbiome variation, followed by cigarette smoking, age, and gender. Among multi-NPC families, especially those with three or more patients, we identify three NPC-enriched taxa with notable heritability, including Gemella sp. (heritability, h2 = 53.1%), Lautropia mirabilis (h2 = 38.8%), and Streptococcus sp. (h2 = 38.0%). Heritable bacteria present a markedly higher heritability in families with increased clustering of NPC and form closely interacting networks, suggesting their role in NPC familial aggregation. These findings open up possibilities for identifying high-risk individuals, enhancing clinical surveillance, and developing personalized prevention and treatment approaches of NPC through microbiome-based strategies.

Despite the progress made in oncological theranostics, cancer remains a global health problem and a leading cause of death worldwide. Multidrug and radiation therapy resistance is an important challenge in cancer treatment. To overcome this great concern in clinical practice, conventional therapies are more and more used in combination with modern approaches to improve the quality of patients' lives. In this review, we emphasize how small biological entities, such as viruses, bacteria, archaea, fungi, protozoans, and microalgae, as well as their related structural compounds and toxins/metabolites/bioactive molecules, can prevent and suppress cancer or regulate malignant initiation, progression, metastasis, and responses to different therapies. All these small biological fighters are free-living or parasitic in nature and, furthermore, viruses, bacteria, archaea, fungi, and protozoans are components of human and animal microbiomes. Recently, polymorphic microbiomes have been recognized as a new emerging hallmark of cancer. Fortunately, there is no limit to the development of novel approaches in cancer biomedicine. Thus, viral vector-based cancer therapies based on genetically engineered viruses, bacteriotherapy, mycotherapy based on anti-cancer fungal bioactive compounds, use of protozoan parasite-derived proteins, nanoarchaeosomes, and microalgae-based microrobots have been more and more used in oncology, promoting biomimetic approaches and biology-inspired strategies to maximize cancer diagnostic and therapy efficiency, leading to an improved patients' quality of life.

Cancer immunotherapy has revolutionized cancer treatment due to its precise, target-specific approach compared with conventional therapies. However, treating solid tumors remains challenging as these tumors are inherently immunosuppressive, and their tumor microenvironment (TME) often limits therapeutic efficacy. Interestingly, certain bacterial species offer a promising alternative by exhibiting an innate ability to target and proliferate within tumor environments. Bacterial structural and functional components can activate innate and adaptive immune responses, creating tumor-suppressive conditions that reduce tumor mass. Additionally, bacteria can deliver effector molecules directly into tumor cells, inducing apoptotic and necrotic cell death. Despite their potential, the use of bacteria in cancer immunotherapy poses risks due to possible toxicities and unpredictable in vivo behavior. Advances in genetic engineering have addressed these concerns by enabling the development of attenuated bacterial strains with enhanced anticancer properties for safer medical applications. This review highlights the role of bacteria in TME modulation, recent strategies to bioengineer bacterial pathogens as therapeutic tools, and the synergistic effects of combining bacteria with other immunotherapies. It also discusses the challenges and prospects of translating this innovative approach into clinical practice, offering a comprehensive overview of bacteria-based cancer immunotherapy's potential to reshape the future of cancer treatment.

Targeted therapy represents a form of cancer treatment that specifically focuses on molecular markers regulating the growth, division, and dissemination of cancer cells. It serves as the cornerstone of precision medicine and is associated with fewer adverse effects compared to conventional chemotherapy, thus enhancing the quality of patient survival. These make targeted therapy as a vital component of contemporary anti-cancer strategies. Although targeted therapy has achieved excellent anti-cancer results, there are still many factors affecting its efficacy. Among the numerous factors affecting anti-cancer treatment, the role of intestinal bacteria and its metabolites are becoming increasingly prominent, particularly in immunotherapy. However, their effects on anticancer targeted therapy have not been systematically reviewed. Herein, we discuss the crosstalk between gut bacteria and anticancer targeted therapies, while also highlighting potential therapeutic strategies and future research directions.

The human gut microbiota, a complex and diverse community of microorganisms, plays a crucial role in maintaining overall health by influencing various physiological processes, including digestion, immune function, and disease susceptibility. The balance between beneficial and harmful bacteria is essential for health, with dysbiosis - disruption of this balance - linked to numerous conditions such as metabolic disorders, autoimmune diseases, and cancers. This review highlights key genera such as Enterococcus, Ruminococcus, Bacteroides, Bifidobacterium, Escherichia coli, Akkermansia muciniphila, Firmicutes (including Clostridium and Lactobacillus), and Roseburia due to their well-established roles in immune regulation and metabolic processes, but other bacteria, including Clostridioides difficile, Salmonella, Helicobacter pylori, and Fusobacterium nucleatum, are also implicated in dysbiosis and various diseases. Pathogenic bacteria, including Escherichia coli and Bacteroides fragilis, contribute to inflammation and cancer progression by disrupting immune responses and damaging tissues. The potential for microbiota-based therapies, such as probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, to improve health outcomes is examined. Future research directions in the integration of multi-omics, the impact of diet and lifestyle on microbiota composition, and advancing microbiota engineering techniques are also discussed. Understanding the gut microbiota's role in health and disease is essential for formulating personalized, efficacious treatments and preventive strategies, thereby enhancing health outcomes and progressing microbiome research.

Colorectal cancer (CRC) is a significant threat to human health. The dynamic equilibrium between probiotics and pathogenic bacteria within the gut microbiota is crucial in mitigating the risk of CRC. An overgrowth of harmful microorganisms in the gastrointestinal tract can result in an excessive accumulation of bacterial toxins and carcinogenic metabolites, thereby disrupting the delicate balance of the microbiota. This disruption may lead to alterations in microbial composition, impairment of mucosal barrier function, potential promotion of abnormal cell proliferation, and ultimately contribute to the progression of CRC. Recently, research has indicated that intestinal presence of Fusobacterium nucleatum (Fn) significantly influences the onset, progression, and metastasis of CRC. Consequently, disrupting the interaction between CRC cells and Fn presents a promising strategy against CRC. Nanomaterials have been extensively utilized in cancer therapy and bacterial infection control, demonstrating substantial potential in treating bacteria-associated tumors. This review begins by elucidating the mechanisms of gut microbiota and the occurrence and progression of CRC, with a particular emphasis on clarifying the intricate relationship between Fn and CRC. Subsequently, we highlight strategies that utilize nanomaterials to disrupt the association between Fn and CRC. Overall, this review offers valuable insight and guidance for leveraging nanomaterials in CRC therapy.

Fusobacterium species are anaerobic Gram-negative bacilli which are uncommon causes of bloodstream infection (BSI). This genus commonly colonises the gastrointestinal tract and can result in significant morbidity.

All blood cultures with growth of Fusobacterium species among residents of Queensland, Australia (population ≈ 5 million) were retrospectively identified over a 20-year period. Clinical, microbiological and outcome information was obtained from state-wide databases.

377 incident Fusobacterium species BSI among 375 individuals for an age and sex-standardised incidence of 4.4 per million residents per year. Median age was 47 years (IQR, 24.9-65.8) and 156 (42%) incident episodes were in females. There was a bimodal frequency distribution with respect to age with peaks occurring around 20 and 65 years, respectively. The most identified source of infection was the abdominal (17%), followed by head and neck (12%). 8% of patients had a septic thrombus present, and 4% had an abscess associated with their BSI. Most isolates were F. nucleatum (142, 38%) and F. necrophorum (140, 37%). 9% of isolates were resistant to penicillin. Older age (aHR 1.02, 95% CI 1.01-1.05), healthcare-associated hospital onset (aHR 3.16, 95% CI 1.35-7.40), and Charlson Comorbidity index (aHR 1.20, 95% CI 1.06-1.35) were all associated with 30-day all cause case-fatality. Oropharyngeal source appeared to be a protective factor (P = 0.02).

Fusobacterium species BSI results in significant morbidity and can cause death in vulnerable patient groups such as the elderly and those with malignancy. An identifiable oropharyngeal source identifies a favourable host.

Fusobacterium nucleatum, a gram-negative anaerobic bacterium, has emerged as a significant player in colorectal cancer (CRC) pathogenesis. The bacterium causes a persistent inflammatory reaction in the colorectal mucosa by stimulating the release of pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α, creating an environment conducive to cancer progression. F. nucleatum binds to and penetrates epithelial cells through adhesins such as FadA, impairing cell junctions and encouraging epithelial-to-mesenchymal transition (EMT), which is associated with cancer advancement. Additionally, the bacterium modulates the host immune system, suppressing immune cell activity and creating conditions favorable for tumor growth. Its interactions with the gut microbiome contribute to dysbiosis, further influencing carcinogenic pathways. Evidence indicates that F. nucleatum can inflict DNA damage either directly via reactive oxygen species or indirectly by creating a pro-inflammatory environment. Additionally, it triggers oncogenic pathways, especially the Wnt/β-catenin signaling pathway, which promotes tumor cell growth and longevity. Moreover, F. nucleatum alters the tumor microenvironment, impacting cancer cell behavior, metastasis, and therapeutic responses. The purpose of this review is to elucidate the molecular mechanisms by which F. nucleatum contributes to CRC. Understanding these mechanisms is crucial for the development of targeted therapies and diagnostic strategies for CRC associated with F. nucleatum.

Fusobacterium nucleatum, an anaerobic Gram-negative bacterium primarily residing in the oral cavity, has garnered significant attention for its emerging role in cancer progression and prognosis. While extensive research has revealed mechanistic links between Fusobacterium nucleatum and colorectal cancer, a comprehensive review spanning its presence and metastatic implications in cancers beyond colorectal origin is conspicuously absent. This paper broadens our perspective from colorectal cancer to various malignancies associated with Fusobacterium nucleatum, including oral, pancreatic, esophageal, breast, and gastric cancers. Our central focus is to unravel the mechanisms governing Fusobacterium nucleatum colonization, initiation, and promotion of metastasis across diverse cancer types. Additionally, we explore Fusobacterium nucleatum's adverse impacts on cancer therapies, particularly within the domains of immunotherapy and chemotherapy. Furthermore, this paper underscores the clinical research significance of Fusobacterium nucleatum as a potential tumor biomarker and therapeutic target, offering a novel outlook on its applicability in cancer detection and prognostic assessment.

As a key component of tumor microenvironment, the microbiota has gradually played a key role in cancer research. Particularly in colorectal cancer, the specific population of microbiota within the tumor shows a strong association with the tumor type. Although the existence and potential role of microbiota in tumors have been recognized, the specific associations between the microbiota and tumor tissue and the mechanism of action still need to be further explored. This paper reviews the discovery, origin, and emerging role of the intratumor microbiota in the immune microenvironment and systematically outlines the oncogenic and metastasis-promoting strategies of the intratumor microbiota. Moreover, it comprehensively and holistically evaluates therapeutic strategies and prognostic performance on the basis of the intratumor microbiota, with the goal of providing strong support for future research and clinical practice.

The intratumoral microbiome plays a significant role in many cancers, such as lung, pancreatic, and colorectal cancer. Pancreatic cancer (PC) is one of the most lethal malignancies and is often diagnosed at advanced stages. Fusobacterium nucleatum (Fn), an anaerobic Gram-negative bacterium primarily residing in the oral cavity, has garnered significant attention for its emerging role in several extra-oral human diseases and, lately, in pancreatic cancer progression and prognosis. It is now recognized as oncobacterium. Fn engages in pancreatic tumorigenesis and metastasis through multifaceted mechanisms, including immune response modulation, virulence factors, control of cell proliferation, intestinal metabolite interactions, DNA damage, and epithelial-mesenchymal transition. Additionally, compelling research suggests that Fn may exert detrimental effects on cancer treatment outcomes. This paper extends the perspective to pancreatic cancer associated with Fn. The central focus is to unravel the oncogenomic changes driven by Fn in colonization, initiation, and promotion of pancreatic cancer development. The presence of Fusobacterium species can be considered a prognostic marker of PC, and it is also correlated to chemoresistance. Furthermore, this review underscores the clinical research significance of Fn as a potential tumor biomarker and therapeutic target, offering a novel outlook on its applicability in cancer detection and prognostic assessment. It is thought that given the role of Fn in tumor formation and metastasis processes via its FadA, FapA, Fap2, and RadD, new therapies for tumor treatment targeting Fn will be developed.

Colorectal cancer (CRC) continues to be a global health concern, necessitating further research into its complex biology and innovative treatment approaches. The etiology, pathogenesis, diagnosis, and treatment of colorectal cancer are summarized in this thorough review along with recent developments. The multifactorial nature of colorectal cancer is examined, including genetic predispositions, environmental factors, and lifestyle decisions. The focus is on deciphering the complex interactions between signaling pathways such as Wnt/β-catenin, MAPK, TGF-β as well as PI3K/AKT that participate in the onset, growth, and metastasis of CRC. There is a discussion of various diagnostic modalities that span from traditional colonoscopy to sophisticated molecular techniques like liquid biopsy and radiomics, emphasizing their functions in early identification, prognostication, and treatment stratification. The potential of artificial intelligence as well as machine learning algorithms in improving accuracy as well as efficiency in colorectal cancer diagnosis and management is also explored. Regarding therapy, the review provides a thorough overview of well-known treatments like radiation, chemotherapy, and surgery as well as delves into the newly-emerging areas of targeted therapies as well as immunotherapies. Immune checkpoint inhibitors as well as other molecularly targeted treatments, such as anti-epidermal growth factor receptor (anti-EGFR) as well as anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibodies, show promise in improving the prognosis of colorectal cancer patients, in particular, those suffering from metastatic disease. This review focuses on giving readers a thorough understanding of colorectal cancer by considering its complexities, the present status of treatment, and potential future paths for therapeutic interventions. Through unraveling the intricate web of this disease, we can develop a more tailored and effective approach to treating CRC.

Fusobacterium nucleatum is a gram-negative anaerobic bacillus associated with colorectal cancer (CRC). We aimed to determine the abundance of F. nucleatum and other CRC-associated bacteria using quantitative real-time polymerase chain reaction (qPCR) analysis to detect the possible correlations between tumor and normal tissues and the relationships between patients' clinical characteristics, diet, and CRC-associated bacteria.

A total of 249 biopsy samples of tumor and paired normal tissues were collected from patients with CRC. Biopsy samples were screened for detection of F. nucleatum using qPCR targeting nusG gene. Bacteroides fragilis, Escherichia coli, and Streptococcus gallolyticus were also detected in the samples using species-specific genes.

The frequencies of detection of F. nucleatum in the tumor and normal tissues of patients with CRC were 43.37 and 24.1%, respectively (P < 0.05). Statistical analysis using cycle threshold (Ct) values from qPCR data and clinical characteristics showed that tumor size, tumor location, and processed meat consumption were significantly correlated with the abundance of F. nucleatum (P < 0.05). The significance of the prevalence of B. fragilis and E. coli in tumor tissues was marginally higher than that in normal tissues (P < 0.1), and the consumption of processed/red meat affected the prevalence of these bacteria (P < 0.05).

Our results showed an association between the presence of F. nucleatum in tumor tissues and CRC, indicating that F. nucleatum may be a potential marker for CRC diagnosis. F. nucleatum is enriched in CRC tissues and is associated with CRC development.

The Fusobacterium genus comprises Gram-negative, obligate anaerobic bacteria that typically reside in the periodontium of the oral cavity, gastrointestinal tract, and female genital tract. The association of Fusobacterial spp. with colorectal tumours is widely accepted, with further evidence that this pathogen may also be implicated in the development of other malignancies. Fusobacterial spp. influence malignant cell behaviours and the tumour microenvironment in various ways, which can be related to the multiple surface adhesins expressed. These adhesins include Fap2 (fibroblast-activated protein 2), CpbF (CEACAM binding protein of Fusobacteria), FadA (Fusobacterium adhesin A) and FomA (Fusobacterial outer membrane protein A). This review outlines the influence of Fusobacteria in promoting cancer initiation and progression, impacts of therapeutic outcomes and discusses potential therapeutic interventions where appropriate.

An intricate relationship exists, and interactions occur between the gut microbiota and colorectal cancer (CRC). Recent studies have indicated that inflammatory reactions stimulated by Fusobacterium nucleatum (Fn) lead to the development of CRC. Radical surgery combined with adjuvant chemotherapy is the primary treatment approach for most CRC patients. This study was designed to evaluate the abundance of Fn as part of the gut microbiota in patients with CRC compared to healthy individuals and to assess the effect of the gut microbiota Fn on patients undergoing adjuvant chemotherapy and those experiencing CRC relapse. There were 201 participants, comprising 50 healthy controls and 151 CRC patients. Stool samples were collected from three CRC groups (postoperatively, chemotherapy and relapse), and the fourth was the healthy control group. The amount of Fn in each sample was analyzed using quantitative loop-mediated isothermal amplification-phenol red (QLAMP-PhR), a novel biomolecular method that targets regions encoding the specific Fn FadA gene. Compared with healthy control stool samples, the Fn levels were significantly elevated in all CRC patient groups (P < 0.001), and it was significantly more frequent in the CRC relapse patients (group C) (P < 0.001). In addition, Fn abundance increased significantly in the distal colon compared to the proximal colon (P < 0.001). Both CRC relapse and chemotherapy exert significant reciprocal effects on the gut microbiota Fn of CRC patients. Microbiota-based intervention may be beneficial for patients during postoperative care, especially in CRC relapsing cases. Registration: This study of the clinical trial has been registered in the ISRCTN registry with study registration number ISRCTN53358464. https://www.isrctn.com/ISRCTN53358464.

The online version contains supplementary material available at 10.1007/s12088-024-01279-6.

Fusobacterium nucleatum (Fn) is significantly associated with poor prognosis in colorectal carcinoma (CRC), however, mechanisms of Fn in DNA mismatch repair (MMR) and microsatellite instability (MSI) in CRC have not been fully elucidated. Clinical samples are collected to analyze the relationship between Fn abundance and microsatellite stability. Tumor cells are treated with Fn to detect the expression of proteins related to toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88), mutS homolog 6 (MSH6), and nuclear factor-κB (NF-κB) signaling pathways, respectively. Combined with the prediction results from TargetScan, the regulatory role of microRNA upstream of MSH6 is demonstrated. The effect of this regulatory axis on CRC development is demonstrated using a nude mouse tumor model. Compared with microsatellite stability (MSS)-type CRC patients, MSI-type showed higher Fn abundance. Fn treatment of CRC cells activated TLR4/Myd88/NF-κB signaling pathway, transcriptionally activating miRNA-155-5p expression, thereby negatively regulating MSH6. Fn treatment accelerated the malignant progression of CRC in mice, and this process is inhibited by miRNA-155-5p antagomir. Fn in CRC upregulated miRNA-155-5p by activating TLR4/NF-κB signaling to inhibit MSH6, and this regulatory pathway may affect MSS of cancer cells.

Previously, many studies have reported changes in the gut microbiota of patients with colorectal cancer (CRC). While CRC is a well-described disease, the relationship between its development and features of the intestinal microbiome is still being understood. Evidence linking Fusobacterium nucleatum enrichment in colorectal tumor tissue has prompted the elucidation of various molecular mechanisms and tumor-promoting attributes. In this review we highlight various aspects of our understanding of the relationship between the development of CRC and the alteration of intestinal microbiome, focusing specifically on the role of F. nucleatum. As the amount of F. nucleatum DNA in CRC tissue is associated with shorter survival, it may potentially serve as a prognostic biomarker, and most importantly may open the door for a role in CRC treatment.

Fusobacterium nucleatum, a gram-negative anaerobic bacterium abundantly found in the human oral cavity, is widely recognized as a key pathobiont responsible for the initiation and progression of periodontal diseases due to its remarkable aggregative capabilities. Numerous clinical studies have linked F. nucleatum with unfavorable prognostic outcomes in various malignancies. In further research, scholars have partially elucidated the mechanisms underlying F. nucleatum's impact on various types of cancer, thus gaining a certain comprehension of the role played by F. nucleatum in cancer. In this comprehensive review, we present an in-depth synthesis of the interplay between F. nucleatum and different cancers, focusing on aspects such as tumor initiation, metastasis, chemoresistance, and modulation of the tumor immune microenvironment and immunotherapy. The implications for cancer diagnosis and treatment are also summarized. The objective of this review is to enhance our comprehension of the intricate relationship between F. nucleatum and oncogenic pathogenesis, while emphasizing potential therapeutic strategies.

The oral pathogen Fusobacterium nucleatum has recently been associated with an elevated risk of colorectal cancer (CRC), endometrial metastasis, chemoresistance, inflammation, metastasis, and DNA damage, along with several other diseases. This study aimed to explore the disruption of protein machinery of F. nucleatum via inhibition of elongation factor thermo unstable (Ef-Tu) protein, through natural products. No study on Ef-Tu inhibition by natural products or in Fusobacterium spp. exists till todate. Ef-Tu is an abundant specialized drug target in bacteria that varies from human Ef-Tu. Elfamycins target Ef-Tu and hence, Enacyloxin IIa was used to generate pharmacophore for virtual screening of three natural product libraries, Natural Product Activity and Species Source (NPASS) (n = 30000 molecules), Tibetan medicinal plant database (n = 54 molecules) and African medicinal plant database (n > 6000 molecules). Peptaibol Septocylindrin B (NPC141050), Hirtusneanoside, and ZINC95486259 were prioritized from these libraries as potential therapeutic candidates. ADMET profiling was done for safety assessment, physiological-based pharmacokinetic modeling in human and mouse for getting insight into drug interaction with body tissues and molecular dynamics was used to assess stability of the best hit NPC141050 (Septocylindrin B). Based on the promising results, we propose further in vitro, in vivo and pharmacokinetic testing on the lead Septocylindrin B, for possible translation into therapeutic interventions.

Acinetobacter baumannii (A. baumannii) has long been recognized primarily as a hospital-acquired pathogen. However, recent studies have uncovered a potential link between this bacterium and oral cancer, necessitating a deeper exploration of this relationship. This review examines the relevance of A. baumannii biofilms in the context of oral cancer development. By synthesizing current knowledge, we seek to provide a comprehensive understanding of this emerging area of research and identify critical directions for future investigations. The review emphasizes the remarkable adaptability, environmental resilience, and antibiotic resistance of A. baumannii, delves into the molecular mechanisms of biofilm formation, and their potential connection to oral cancer progression. The review also evaluates how biofilm colonization on oral surfaces and medical devices, along with its role in chronic infections, inflammation, and increased antimicrobial resistance, could contribute to creating a microenvironment favourable for tumor development. This review underscores the broader healthcare implications of A. baumannii biofilms, evaluates current strategies for their prevention and eradication, and calls for interdisciplinary research in this emerging field. By shedding light on the complex interactions between A. baumannii biofilms and oral cancer, it aims to stimulate further research and guide the development of new diagnostic, preventive, and therapeutic strategies in both microbiology and oncology.

Biofilms are complex, highly organized structures formed by microorganisms, with functional cell arrangements that allow for intricate communication. Severe clinical challenges occur when anaerobic bacterial species establish long-lasting infections, especially those involving biofilms. These infections can occur in device-related settings (e.g., implants) as well as in non-device-related conditions (e.g., inflammatory bowel disease). Within biofilms, bacterial cells communicate by producing and detecting extracellular signals, particularly through specific small signaling molecules known as autoinducers. These quorum-sensing signals are crucial in all steps of biofilm formation: initial adhesion, maturation, and dispersion, triggering gene expression that coordinates bacterial virulence factors, stimulates immune responses in host tissues, and contributes to antibiotic resistance development. Within anaerobic biofilms, bacteria communicate via quorum-sensing molecules such as N-Acyl homoserine lactones (AHLs), autoinducer-2 (AI-2), and antimicrobial molecules (autoinducing peptides, AIPs). To effectively combat pathogenic biofilms, understanding biofilm formation mechanisms and bacterial interactions is essential. The strategy to disrupt quorum sensing, termed quorum quenching, involves methods like inactivating or enzymatically degrading signaling molecules, competing with signaling molecules for binding sites, or noncompetitively binding to receptors, and blocking signal transduction pathways. In this review, we comprehensively analyzed the fundamental molecular mechanisms of quorum sensing in biofilms formed by anaerobic bacteria. We also highlight quorum quenching as a promising strategy to manage bacterial infections associated with anaerobic bacterial biofilms.

Bacterial biofilms are pervasive and recalcitrant to current antimicrobials, causing numerous infections. Iron oxide nanozymes, including an FDA-approved formulation, ferumoxytol (FMX), show potential against biofilm infections via catalytic activation of hydrogen peroxide (H2O2). However, clinical evidence regarding the efficacy and therapeutic mechanisms of FMX is lacking. Here, we investigate whether FMX nanozymes can treat chronic biofilm infections and compare their bioactivity to that of the gold standard sodium hypochlorite (NaOCl), a potent but caustic disinfectant. Clinical performance was assessed in patients with apical periodontitis, an intractable endodontic infection affecting half of the global adult population. Data show robust antibiofilm activity by a single application of FMX with H2O2 achieving results comparable to those seen with NaOCl without adverse effects. FMX binds efficiently to the bacterial pathogens Enterococcus faecalis and Fusobacterium nucleatum and remains catalytically active without being affected by dental tissues. This allows for effective eradication of endodontic biofilms via on-site free radical generation without inducing cytotoxicity. Unexpectedly, FMX promotes growth of stem cells of the apical papilla (SCAPs), with transcriptomic analyses revealing upregulation of proliferation-associated pathways and downregulation of cell cycle suppressor genes. Notably, FMX activates SCAP pluripotency and WNT/NOTCH signaling that induces its osteogenic capacity. Together, these results show that FMX nanozymes are clinically effective against severe chronic biofilm infection with pathogen targeting and unique stem cell-stimulatory properties, offering a regenerative approach to antimicrobial therapy.

Fusobacterium nucleatum (Fn) has been extensively studied for its connection to colorectal cancer (CRC) and its potential role in chemotherapy resistance. Studies indicate that Fn is commonly found in CRC tissues and is associated with unfavorable prognosis and treatment failure. It has been shown that Fn promotes chemoresistance by affecting autophagy, a cellular process that helps cells survive under stressful conditions. Additionally, Fn targets specific signaling pathways that activate particular microRNAs and modulate the response to chemotherapy. Understanding the current molecular mechanisms and investigating the importance of Fn-inducing chemoresistance could provide valuable insights for developing novel therapies. This review surveys the role of Fn in tumor proliferation, metastasis, and chemoresistance in CRC, focusing on its effects on the tumor microenvironment, gene expression, and resistance to conventional chemotherapy drugs. It also discusses the therapeutic implications of targeting Fn in CRC treatment and highlights the need for further research.

A significant percentage of cancer-related fatalities are caused by breast cancer (BC). Fusobacterium nucleatum (Fn) is a common Gram-negative anaerobic bacterium found in various inflammatory diseases, and there are also reports suggesting its involvement in cancer progression. This study discussed molecular mechanisms of Fn-induced immune escape in BC cells.

mRNA and protein PD-L1 expression in BC cells were detected using qRT-PCR and western blot (WB). WB assayed NF-κB-related marker expressions (p-p65, p-65, p-p50, p-50) in cells. PD-L1 expression levels on the cell surface, apoptosis and proliferation of CD8+ T and BC cells were measured via flow cytometry. ELISA tested TNFα, IFNγ, and granzyme B to assess the activation level of CD8+ T cells. The secretion level of LDH in the co-culture system was tested using an LDH detection kit to evaluate the cell death rate.

BC cells stimulated by Fn can blunt tumor-killing of CD8+ T cells and their vitality. Fn treatment upregulates PD-L1 in BC cells. Rescue experiments using NF-κB inhibitors suggested that Fn treatment mediated NF-κB signaling and fostered PD-L1 expression in cancer cells. Fn repressed the killing effect of CD8+ T cells on BC cells by triggering the NF-κB/PD-L1 signaling pathway.

Fn helps BC cells evade the killing effect of CD8+ T cells through the NF-κB/PD-L1 pathway.

Fusobacterium nucleatum (F. nucleatum), an anaerobic, gram-negative microbe, commonly found in human dental biofilm and the gut flora. It has long been known to have a higher concentration in periodontal disease and has recently been implicated in both oral and distant cancers such as colorectal, gastrointestinal, esophageal, breast, pancreatic hepatocellular, and genitourinary cancers. However, the mechanism of its involvement in the development of cancer has not been fully discussed. This review aims to cover biological molecular and clinical aspects of F. nucleatum and cancers.

Studies indicate F. nucleatum promotes tumor development through chronic inflammation, immune evasion, cell proliferation activation, and direct cell interactions, as in oral squamous cell carcinoma (OSCC). In colorectal cancer (CRC), F. nucleatum contributes to tumorigenesis through β-catenin signaling and NF-κB activation. It also induces autophagy, leading to chemoresistance in CRC and esophageal cancers, and enhances tumor growth and metastasis in breast cancer by reducing T-cell infiltration. F. nucleatum is linked to carcinogenesis and increased bacterial diversity in OSCC, with improved oral hygiene potentially preventing OSCC. F. nucleatum triggers cancer by causing mutations and epigenetic changes through cytokines and reactive oxygen species. It also promotes chemoresistance in CRC. F. nucleatum may potentially serve as a diagnostic tool in various cancers, with non-invasive detection methods available. Further investigation is needed to discover its potential in the diagnosis and treatment of OSCC and other cancers.

The aim of the present study is to explore the possible association between periodontitis and upper gastrointestinal (UGI) cancers, including esophageal and gastric cancers, utilizing the Mendelian randomization method.

In this research, we utilized the Mendelian randomization method to examine the causal association between periodontitis and UGI cancers. Genome-wide association studies data for periodontitis were obtained from the Gene-Lifestyle Interactions in Dental Endpoints consortium, while UGI cancers' data were accessed from FinnGen's Biobank. After rigorously screening instrumental variables for periodontitis, we analyzed them with UGI cancers primarily using the inverse variance weighted. Finally, to identify outliers, the results were subjected to a leave-one-out sensitivity analysis.

Inverse variance weighted (fixed effect) results revealed that periodontitis is a risk factor for gastric cancer (OR = 1.7735, 95% CI: 1.1576 to 2.7170, P = 0.0085). As for esophageal cancer, no statistically significant correlation was observed. Furthermore, no outliers were detected in any of the results.

Our two-sample Mendelian randomization study obviously demonstrates a significant positive association between periodontitis and gastric cancer, while no statistically significant correlation was found for esophageal cancer.

Fusobacterium nucleatum is an oral commensal bacterium that can act as an opportunistic pathogen and is implicated in diseases such as periodontitis, adverse pregnancy outcomes, colorectal cancer, and Alzheimer's disease. F. nucleatum synthesizes lanthionine for its peptidoglycan, rather than meso-2,6-diaminopimelic acid (DAP) used by most Gram-negative bacteria. Despite lacking the biosynthetic pathway for DAP, the genome of F. nucleatum ATCC 25586 encodes a predicted DAP epimerase. A recent study hypothesized that this enzyme may act as a lanthionine epimerase, but the authors found a very low turnover rate, suggesting that this enzyme likely has another more favored substrate. Here, we characterize this enzyme as a histidine racemase (HisR), and found that catalytic turnover is ∼10,000× faster with L-histidine than with L,L-lanthionine. Kinetic experiments suggest that HisR functions as a cofactor-independent racemase and that turnover is specific for histidine, while crystal structures of catalytic cysteine to serine mutants (C67S or C209S) reveal this enzyme in its substrate-unbound, open conformation. Currently, the only other reported cofactor-independent histidine racemase is CntK from Staphylococcus aureus, which is used in the biosynthesis of staphylopine, a broad-spectrum metallophore that increases virulence of S. aureus. However, CntK shares only 28% sequence identity with HisR, and their genes exist in different genomic contexts. Knockout of hisR in F. nucleatum results in a small but reproducible lag in growth compared to WT during exponential phase, suggesting that HisR may play a role in growth of this periodontal pathogen.

The risk of colorectal cancer [CRC] is increased in patients with inflammatory bowel disease [IBD], particularly in extensive ulcerative colitis [UC] and Crohn's colitis. Gut microbiota have been implicated in the pathogenesis of CRC via multiple mechanisms, including the release of reactive oxygen species and genotoxins, and induction of inflammation, as well as activation of the immune response. Gut microbiota can enhance their carcinogenic and proinflammatory properties by organising into biofilms, potentially making them more resistant to the host's immune system and to antibiotics. Colonic biofilms have the capacity to invade colonic tissue and accelerate tumorigenesis in tumour-prone models of mice. In the context of IBD, the prevalence of biofilms has been estimated to be up to 95%. Although the relationship between chronic inflammation and molecular mediators that contribute to IBD-associated CRC is well established, the role of gut microbiota and biofilms in this sequence is not fully understood. Because CRC can still arise in the absence of histological inflammation, there is a growing interest in identifying chemopreventive agents against IBD-associated CRC. Commonly used in the treatment of UC, 5-aminosalicylates have antimicrobial and anticarcinogenic properties that might have a role in the chemoprevention of CRC via the inhibition or modulation of carcinogenic gut microbiota and potentially of biofilm formation. Whether biologics and other IBD-targeted therapies can decrease the progression towards dysplasia and CRC, via mechanisms independent of inflammation, is still unknown. Further research is warranted to identify potential new microbial targets in therapy for chemoprevention of dysplasia and CRC in IBD.

This study explores and verifies potential molecular targets through which KRAS mutations regulate the colonization of Fusobacterium nucleatum (FN) in colorectal cancer (CRC). This study combined multiple bioinformatics methods and biological assays. Through The Cancer Genome Atlas, Gene Expression Omnibus, Human Protein Atlas, immunohistochemistry, and co-culture assays, we further confirmed the differential expression of SERTAD4 in CRC. We delved deeper into examining how expression of SERTAD4 is linked with immune cell infiltration and the enrichment of potential pathways. Lastly, through bacterial phenotypic assays, we validated the function of SERTAD4. As a molecule associated with KRAS mutations and FN infection, the expression levels of SERTAD4 were downregulated in CRC. The diagnostic efficacy of SERTAD4 for CRC is not inferior to that of CEA. Low expression of SERTAD4 is associated with poorer overall survival in CRC. Correlation analysis found that increased expression of SERTAD4 is associated with various immune cell infiltrations and immune checkpoint genes. Finally, bacterial adhesion and invasion assays verify that SERTAD4 inhibits the adhesion and invasion abilities of FN in CRC. This study demonstrates that SERTAD4 exerts a protective role in CRC by inhibiting the colonization of FN.

This review aims to critically analyze the pathways of interaction and the pathogenic mechanisms linking periodontitis and oral bacteria with the initiation/progression of cancer at different body compartments. A higher risk of head and neck cancer has been consistently associated with periodontitis. This relationship has been explained by the local promotion of dysbiosis, chronic inflammation, immune evasion, and direct (epi)genetic damage to epithelial cells by periodontal pathobionts and their toxins. Epidemiological reports have also studied a possible link between periodontitis and the incidence of other malignancies at distant sites, such as lung, breast, prostate, and digestive tract cancers. Mechanistically, different pathways have been involved, including the induction of a chronic systemic inflammatory state and the spreading of oral pathobionts with carcinogenic potential. Indeed, periodontitis may promote low-grade systemic inflammation and phenotypic changes in the mononuclear cells, leading to the release of free radicals and cytokines, as well as extracellular matrix degradation, which are all mechanisms involved in carcinogenic and metastatic processes. Moreover, the transient hematogenous spill out or micro-aspiration/swallowing of periodontal bacteria and their virulence factors (i.e., lipopolysaccharides, fimbriae), may lead to non-indigenous bacterial colonization of multiple microenvironments. These events may in turn replenish the tumor-associated microbiome and thus influence the molecular hallmarks of cancer. Particularly, specific strains of oral pathobionts (e.g., Porphyromonas gingivalis and Fusobacterium nucleatum) may translocate through the hematogenous and enteral routes, being implicated in esophageal, gastric, pancreatic, and colorectal tumorigenesis through the modulation of the gastrointestinal antitumor immune system (i.e., tumor-infiltrating T cells) and the increased expression of pro-inflammatory/oncogenic genes. Ultimately, the potential influence of common risk factors, relevant comorbidities, and upstream drivers, such as gerovulnerability to multiple diseases, in explaining the relationship cannot be disregarded. The evidence analyzed here emphasizes the possible relevance of periodontitis in cancer initiation/progression and stimulates future research endeavors.

It has long been considered that the oral microbiome is tightly connected to oral health and that dysbiotic changes can be detrimental to the occurrence and progression of dysplastic oral mucosal lesions or oral cancer. Improved understanding of the concepts of microbial dysbiosis together with advances in high-throughput molecular sequencing of these pathologies have charted in greater microbiological detail the nature of their clinical state. This review discusses the bacteriome and mycobiome associated with oral mucosal lesions, oral candidiasis, and oral squamous cell carcinoma, aiming to delineate the information available to date in pursuit of advancing diagnostic and prognostic utilities for oral medicine.