Dysbiosis and pathobionts contribute to inflammation and the risk of colitis-associated carcinoma (CAC) in animal models, but their roles in humans with this uncommon disease are unknown. We identified microbiome differences in human CAC compared with longstanding inflammatory bowel disease (IBD) and sporadic colorectal carcinoma (CRC). Twenty-four CAC resections were matched with CRC and IBD controls. Methods included histopathology, 16S rDNA metagenomics, and pathobiont-specific qPCR. Beta diversity differed by diagnosis (PERMANOVA p = 0.007). The distinguishing taxa included Akkermansia enriched in CRC, and Bacteroides spp. enriched in IBD. The non-neoplastic mucosae presented distinct beta diversity (p = 0.005), but the CAC/CRC tumor microbiomes were similar (p = 0.7). Within metastases and margins, Enterobacteriaceae were enriched in CAC, and Bacteroidales in CRC. Pathobiont-specific qPCR confirmed a greater frequency of pks+ E. coli and enterotoxigenic Bacteroides fragilis in CAC than IBD. High alpha diversity was associated with active inflammation, advanced cancer stage, and shorter overall survival (log-rank p = 0.008). Mucosal microbiomes distinguish CAC from longstanding IBD, implicating pathobionts as markers for disease progression. Integrating our findings with prior animal model research, pathobionts promote carcinogenesis in IBD patients through genotoxicity and host cell signaling.

Fusobacterium nucleatum (F. nucleatum) is an anaerobic bacterium known for its association with periodontal disease and oral infections. It has been implicated in the development of gastrointestinal diseases such as inflammatory bowel disease and colorectal cancer. Ulcerative colitis (UC), which is characterized by chronic inflammation of the colon, is a condition of unknown etiology with a rising incidence rate, significantly affecting the quality of life for patients. The increased intestinal permeability during UC may facilitate the adherence or invasion of F. nucleatum into the damaged intestinal barrier, leading to exacerbated inflammation.

This article introduces the concept of the oral-gut axis, reviewing existing literature to analyze the role of F. nucleatum in the pathogenesis of UC and exploring its potential pathogenic mechanisms. It also summarizes the latest advances in treating patients with UC who have F. nucleatum and looks forward to prospective therapeutic strategies and the translational prospects of F. nucleatum within the oral-gut axis.

F. nucleatum may be a key player in the pathogenesis of UC, likely due to its invasiveness during periods of increased intestinal permeability. The paper also discusses innovative approaches for the prevention and management of UC exacerbated by F. nucleatum, paving the way for more effective treatment of UC.

The review offers new insights into the complex relationship between the oral microbiome and intestinal diseases, enhancing our understanding of their dynamic interactions. There is a paucity of literature on therapeutic approaches, indicating a need for further clinical research.

The Wnt/β-catenin signalling pathway normally maintains cellular and tissue homeostasis by regulating cellular differentiation and survival in a controlled manner. An aberrantly regulated Wnt/β-catenin signalling pathway can transform into an oncogenic pathway, which is associated with Colorectal cancer (CRC) as well as other cancers. CRC is one of the most frequently occurring gastrointestinal cancers worldwide. In CRC tissues, deregulation of Wnt/β-catenin pathway is observed, which indicates that this oncogenic pathway directly promotes CRC malignancy, cell migration, angiogenesis, chemoresistance, as well as shorter lifespan of a patient. Growing evidence suggests that human commensal microbes have a strong association with carcinogenesis, particularly the prevalence and high enrichment of Fusobacterium nucleatum in CRC progression. The Wnt/β-catenin pathway is one of the targeted pathways by F. nucleatum in CRC, where Fusobacterium adhesin attaches to E-cadherin to initiate infection. Also, Wnt/β-catenin pathway can be a potential target for the treatment of both CRC and F. nucleatum-positive CRC. Here, we discuss the underlying mechanisms of F. nucleatum-positive CRC development through modulation of Wnt/β-catenin signalling and its possibility for the application in targeted therapy of F. nucleatum-positive CRC.

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.

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.

Colorectal cancer (CRC) is the second most common cause of cancer-related deaths globally. The gut microbiota, along with adenomatous polyps (AP), has emerged as a plausible contributor to CRC progression. This study aimed to scrutinize the impact of the FadA antigen derived from Fusobacterium nucleatum on the expression levels of the ANXA2 ceRNA network and assess its relevance to CRC advancement.

The functions of ANXA2 and LINC00460 in CRC have been partially clarified. According to our previous study to identify shared MicroRNA-Interaction-Targets (MITs) between ANXA2 and LINC00460, TargetScanHuman (V7.2) and miRDB databases have been used respectively. The Bioinformatics and Evolutionary Genomics web tool was employed to intersect the sets of shared microRNAs and their common targets. Then, the ANXA2 ceRNA network was constructed. Subsequently, the mRNA, miRNA, and lncRNA expression levels were examined in intestinal biopsy specimens from 30 healthy controls, 30 Adenoma patients, and 30 cases of CRC stage I using qRT-PCR.

Elevated expression levels of FadA, ANXA2, hsa-let-7a-2, and LINC00460 were observed in CRC specimens, followed by AP cases, in comparison to samples from normal individuals. Application of the Spearman test revealed a strong and significant correlation between FadA and LINC00460 (rS = 0.9311, p < 0.0001). Also, the functional analysis of ANXA2 revealed its impact on CRC progression through JAK-STAT and Hippo signaling pathways.

FadA appears to potentiate CRC progression by inducing the upregulation of LINC00460, consequently leading to the hyperexpression of ANXA2 through the ceRNA network.

Oral squamous cell carcinoma (OSCC) is the most common manifestation of oral cancer. It has been proposed that periodontal pathogens contribute to OSCC progression, mainly by their virulence factors. However, the main periodontal pathogen and its mechanism to modulate OSCC cells remains not fully understood. In this study we investigate the main host-pathogen pathways in OSCC by computational proteomics and the mechanism behind cancer progression by the oral microbiome. The main host-pathogen pathways were analyzed in the secretome of biopsies from patients with OSCC and healthy controls by mass spectrometry. Then, functional assays were performed to evaluate the host-pathogen pathways highlighted in oral cancer. Host proteins associated with LPS response, cell migration/adhesion, and metabolism of amino acids were significantly upregulated in the human cancer proteome, whereas the complement cascade was downregulated in malignant samples. Then, the microbiome analysis revealed large number and variety of peptides from Fusobacterium nucleatum (F. nucleatum) in OSCC samples, from which several enzymes from the L-glutamate degradation pathway were found, indicating that L-glutamate from cancer cells is used as an energy source, and catabolized into butyrate by the bacteria. In fact, we observed that F. nucleatum modulates the cystine/glutamate antiporter in an OSCC cell line by increasing SLC7A11 expression, promoting L-glutamate efflux and favoring bacterial infection. Finally, our results showed that F. nucleatum and its metabolic derivates promote tumor spheroids growth, spheroids-derived cell detachment, epithelial-mesenchymal transition and Galectin-9 upregulation. Altogether, F. nucleatum promotes pro-tumoral mechanism in oral cancer.

Fusobacterium can contribute to oral diseases, but also pose as a systemic risk factor. This genus, and especially F. nucleatum, can be found in colorectal cancer (CRC) tissue and is involved in multiple aspects of this type of cancer. Previous studies indicated a possible oral origin of these bacteria; however, stronger evidence is needed to reach a definitive conclusion. This pilot study aimed to establish a method to successfully compare, at the strain level, fusobacteria from the oral cavity and CRC resection material for future cohort studies of CRC patients.

In a first cohort of eight periodontitis patients, gingival crevicular fluid and saliva were collected. Fusobacterium was isolated on two different media. In a second cohort, saliva and CRC resection material were collected from ten CRC patients. These samples were used for screening of Fusobacterium with culturing, 16S rRNA gene profiling and a PCR-based approach.

In the first cohort, different Fusobacterium species were identified in GCF and saliva samples. However, as the total yield of Fusobacterium seemed slightly higher in saliva samples, it was therefore preferred for subsequent sample collection. Thus, in the second cohort, patient-matched saliva and CRC resection material were screened for Fusobacterium and this showed that nine patients were culture-positive in the saliva samples; however, no Fusobacterium could be isolated from the resection material. On the other hand, 16S rRNA gene profiling of the resection material indicated that eight CRC patients were positive for Fusobacterium. All eight of these patients carried Fusobacterium in their saliva, indicated by both marker gene PCR and culture-based screening.

These pilot results are compatible with data from previous studies, indicating a possible link between oral and CRC-associated Fusobacterium, and a more in-depth analysis of specific strains and their characteristics in a larger cohort is justified.

The protocol was registered at clinicaltrials.gov (NCT05945082).

The rise in the incidence of cancer globally has led to a heightened interest in targeted therapies as a form of anticancer treatment. Key oncogenic targets, including epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and kirsten rat sarcoma viral oncogene homologue (KRAS), have emerged as focal points in the development of targeted agents. Research has investigated the impact of gut microbiota on the efficacy of various anticancer therapies, such as immunotherapy, chemotherapy, and radiotherapy. However, a notable gap exists in the literature regarding the relationship between gut microbiota and targeted agents. This review emphasizes how specific gut microbiota and gut microbiota metabolites, including butyrate, propionate, and ursodeoxycholic acid, interact with oncogenic pathways to modulate anti-tumor effects. Conversely, deoxycholic acid, lipopolysaccharide, and trimethylamine n-oxide may exert pro-tumor effects. Furthermore, modulation of the gut microbiota influences glucose and lipid metabolism, thereby enhancing the response to anti-KRAS agents and addressing diarrhea induced by tyrosine kinase inhibitors. By elucidating the connection between gut microbiota and the EGFR/VEGF/KRAS pathways, this review provides valuable insights for advancing targeted cancer therapy and optimizing treatment outcomes in clinical settings.

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.

Colorectal cancer (CRC) is one of the most prevalent and lethal malignant tumors globally, posing significant health risks and societal burdens. Recently, advancements in next-generation sequencing technology have identified CRC intratumoral microbiota, thereby opening up novel avenues for further research. This review synthesizes the current advancements in CRC intratumoral microbiota and their impact on CRC progression and discusses the disparities in the relative abundance and community composition of CRC intratumoral microbiota across various colorectal tumors based on their anatomical location and molecular subtypes, as well as the tumor stages, and spatial tumor distribution. Intratumoral microbiota predominantly influence CRC development by modulating colonic epithelial cells, tumor cells, and the tumor microenvironment. Mechanistically, they can cause DNA damage, apoptosis and epithelial-mesenchymal transition. The effects of different intratumoral microbiota on CRC have been shown to be two-fold. In the future, to address the limitations of existing studies, it is important to develop comprehensive experimental protocols and suitable in vitro models for elucidating more mechanisms of intratumoral microbiota on CRC, which will facilitate the clinical application of microbe-related therapeutic strategies in CRC and potentially other tumors.

Several studies have reported the effects of Fusobacterium nucleatum stimulation on oral cancer cells. However, given that these studies typically span a stimulation period of three days to eight days, the in vitro studies conducted to date may not fully mimic the oral cancer environment, which involves constant exposure to oral commensal bacteria. This study aimed to elucidate the effects of prolonged and persistent Fusobacterium nucleatum infection on oral cancer cells.

Human tongue squamous cell carcinoma (SCC) cells were continuously stimulated with Fusobacterium nucleatum for two or four weeks, then experimentally evaluated.

Prolonged, persistent Fusobacterium nucleatum stimulation increased the cells' proliferative, invasive, and migratory capacities, decreased their expression of epithelial markers, and increased their expression of mesenchymal markers progressively with time. The cells also adopted a spindle-shaped morphology and cell-to-cell contact dependence was progressively lost, suggesting time-dependent occurrence of epithelial-mesenchymal transition. Furthermore, mRNA levels of CD44, a cancer stem cell marker, were time-dependently upregulated. When SCC cells were stimulated with Fusobacterium nucleatum for four weeks in the presence of dexamethasone, Fusobacterium nucleatum induced epithelial-mesenchymal transition was inhibited.

Epithelial-mesenchymal transition in human tongue SCC cells was time-dependently induced by prolonged, persistent Fusobacterium nucleatum stimulation and inhibited by dexamethasone. Routine decontamination of the oral cavity may be crucial for controlling tumor invasion and metastasis.

Inflammatory bowel disease (IBD) is a recurrent chronic intestinal disorder that includes ulcerative colitis (UC) and Crohn's disease (CD). Its pathogenesis involves intricate interactions between pathogenic microorganisms, native intestinal microorganisms, and the intestinal immune system via the oral-gut axis. The strong correlation observed between oral diseases and IBD indicates the potential involvement of oral pathogenic microorganisms in IBD development. Consequently, therapeutic strategies targeting the proliferation, translocation, intestinal colonization and exacerbated intestinal inflammation of oral microorganisms within the oral-gut axis may partially alleviate IBD. Tea consumption has been identified as a contributing factor in reducing IBD, with epigallocatechin gallate (EGCG) being the primary bioactive compound used for IBD treatment. However, the precise mechanism by which EGCG mediates microbial crosstalk within the oral-gut axis remains unclear. In this review, we provide a comprehensive overview of the diverse oral microorganisms implicated in the pathogenesis of IBD and elucidate their colonization pathways and mechanisms. Subsequently, we investigated the antibacterial properties of EGCG and its potential to attenuate microbial translocation and colonization in the gut, emphasizing its role in attenuating exacerbations of IBD. We also elucidated the toxic and side effects of EGCG. Finally, we discuss current strategies for enhancing EGCG bioavailability and propose novel multi-targeted nano-delivery systems for the more efficacious management of IBD. This review elucidates the role and feasibility of EGCG-mediated modulation of the oral-gut axis microbiota in the management of IBD, contributing to a better understanding of the mechanism of action of EGCG in the treatment of IBD and the development of prospective treatment strategies.

Colitis is an important risk factor for the occurrence of colorectal cancer (CRC), and the colonization of Fusobacterium nucleatum (Fn) in the intestines accelerates this transformation process. Banxia Xiexin Decoction (BXD), originating from Shanghanlun, is a classic prescription for treating gastrointestinal diseases. Current researches indicate that BXD can effectively delay the colitis-to-cancer transition, but it is still unclear whether it can inhibit Fn colonization to achieve this delaying effect.

This study explored the effect and mechanism of BXD in inhibiting Fn intestinal colonization to delay colitis-to-cancer transition.

We constructed a mouse model of colitis-to-cancer transition by regularly gavaging Fn combined with azoxymethane (AOM)/dextran sodium sulfate (DSS), and administered BXD by gavage. We monitored the body weight of mice, measured the length and weight of their colons, and calculated the disease activity index (DAI) score. The growth status of colon tumors was observed by hematoxylin and eosin (H&E) staining, and the changes in gut microbiota in each group of mice were detected by 16S rDNA analysis. Immunohistochemistry was used to detect the expression of E-cadherin and β-catenin in colon tissues, and immunofluorescence was used to observe the infiltration of M2 macrophages in colon tissues. In cell experiments, we established a co-culture model of Fn and colon cancer cells and intervened with BXD-containing serum. Malignant behaviors such as cell proliferation, invasion, and migration were detected, as well as changes in their cell cycle. We examined the protein levels of E-cadherin, β-catenin, Axin2, and Cyclin D1 in each group were detected by Western blot. We used US1 strain (fadA-) as a control and observed the effects of BXD-containing serum on Fn attachment and invasion of colon cancer cells through attachment and invasion experiments.

BXD can inhibit the colitis-to-cancer transition in mice infected with Fn, reduce crypt structure damage, improve gut microbiota dysbiosis, upregulate E-cadherin and decrease β-catenin expression, and reduce infiltration of M2 macrophages, thus inhibiting the process of colitis-to-cancer transition. Cell experiments revealed that BXD-containing serum can inhibit the proliferation, migration, and invasion of colon cancer cells infected with Fn and regulate their cell cycle. More importantly, we found that BXD-containing serum can inhibit the binding of Fn's FadA adhesin to E-cadherin, reduce Fn's attachment and invasion of colon cancer cells, thereby downregulating the E-cadherin/β-catenin signaling pathway.

These findings show that BXD can inhibit Fn colonization by interfering with the binding of FadA to E-cadherin, reducing the activation of the E-cadherin/β-catenin signaling pathway, and ultimately delaying colitis-to-cancer transition.

Chronic intestinal inflammatory diseases play a crucial role in the onset of colorectal cancer (CRC). Effectively impeding the progression of colitis-associated colorectal cancer (CAC) can be instrumental in hindering CRC development. Wu-Mei-Pill (WMP), a formulation comprising various herbal extracts, is clinically employed for CAC treatment, yet the underlying mechanism of WMP's efficacy in CAC remains unclear. Our study firstly demonstrated the effects and mechanisms of WMP on transcriptional and metabolic levels based on integrated transcriptomics and untargeted metabolomics and relative experimental validations.

A CAC mouse model was established through a single injection of azoxymethane (AOM) followed by intermittent dextran sodium sulfate (DSS) intervention, with subsequent WMP administration. Initially, the therapeutic impact of WMP on the CAC model was assessed by observing survival rate, body weight change, colon length, tumor number, tumor load, and pathological changes in the colon tissue of CAC mice post-WMP intervention. Subsequently, differential genes and metabolites in the colorectal tissue of CAC mice following WMP intervention were identified through transcriptomics and non-targeted metabolomics. Finally, the influence of WMP on the peroxisome proliferator activated receptor (PPAR) pathway, Wnt pathway, and CC motif chemokine ligand 3 (CCL3)/ CC motif chemokine receptor 1 (CCR1) axis in CAC mice was verified through western blot, immunofluorescence, and ELISA based on the results of transcriptomics and non-targeted metabolomics.

WMP intervention enhanced survival, alleviated body weight loss, shortened colon length, tumor occurrence, and pathological changes in the colorectal tissue of CAC mice, such as glandular damage, tumourigenesis, and inflammatory cell infiltration. Transcriptomic and non-targeted metabolomic results revealed that WMP intervention up-regulated the expression of key regulatory mechanisms of fatty acid oxidation PPAR pathway-related genes (Pparg, Ppara, Cpt1a, and Acadm) and metabolites (L-carnitine and L-palmitoylcarnitine). Additionally, it down-regulated Wnt pathway-related genes (Wnt3, Axin2, Tcf7, Mmp7, Lgr5, Wnt5a, Fzd6, Wnt7b, Lef1, and Fzd10 etc.) and pro-inflammatory related genes (Il1b, Il6, Il17a, Ccl3, and Ccr1 etc.). Experimental validation demonstrated that WMP up-regulated PPAR pathway-related proteins [PPARγ, PPARα, carnitine palmitoyltransferase 1A (CPT1A), and acyl-CoA dehydrogenase medium chain (ACADM)] in the colorectal tissue of CAC mice. It also down-regulated Wnt pathway-related proteins [β-catenin, T-cell factor (TCF), lymphoid enhancer-binding factor (LEF), and matrix metallopeptidase 7 (MMP7)], inhibited the nuclear translocation of the key transcription factor β-catenin in the Wnt pathway, and suppressed epithelial-to-mesenchymal transition (EMT) activation induced by the Wnt pathway (up-regulated E-cadherin and down-regulated Vimentin). Furthermore, WMP intervention reduced pro-inflammatory factors [interleukin (IL)-6, IL-1β, and IL-17A] and decreased CCL3/CCR1 axis factors, including CCL3 protein levels and diminished F4/80+CCR1+ positive expressed cells.

WMP significantly inhibits CAC tumorigenesis by up-regulating PPARα-mediated fatty acid oxidation, inhibiting the Wnt signaling pathway-mediated EMT, and suppressing CCL3/CCR1-mediated inflammatory responses.

Metastasis poses a major challenge in colorectal cancer (CRC) treatment and remains a primary cause of mortality among patients with CRC. Recent investigations have elucidated the involvement of disrupted gut microbiota homeostasis in various facets of CRC metastasis, exerting a pivotal influence in shaping the metastatic microenvironment, triggering epithelial-mesenchymal transition (EMT), and so on. Moreover, therapeutic interventions targeting the gut microbiota demonstrate promise in enhancing the efficacy of conventional treatments for metastatic CRC (mCRC), presenting novel avenues for mCRC clinical management. Grounded in the "seed and soil" hypothesis, this review consolidates insights into the mechanisms by which imbalanced gut microbiota promotes mCRC and highlights recent strides in leveraging gut microbiota modulation for the clinical prevention and treatment of mCRC. Emphasis is placed on the considerable potential of manipulating gut microbiota within clinical settings for managing mCRC.

Resveratrol is a natural phytoalexin that has anti-inflammatory properties, reverses doxorubicin resistance, and inhibits epithelial-mesenchymal transition (EMT) in many types of cancer cells. Fusobacterium nucleatum is reportedly enriched in oral squamous cell carcinoma (OSCC) tissues compared to adjacent normal tissues, sparking interest in the relationship between F. nucleatum and OSCC. Recently, F. nucleatum was shown to be associated with EMT in OSCC. In the present study, we aimed to investigate the effects of the natural plant compound resveratrol on F. nucleatum-induced EMT in OSCC.

F. nucleatum was co-cultured with OSCC cells, with a multiplicity of infection (MOI) of 300:1. Resveratrol was used at a concentration of 10 μM. Cell Counting Kit-8 and wound healing assays were performed to examine the viability and migratory ability of OSCC cells. Subsequently, real-time RT-PCR was performed to investigate the gene expression of EMT-related markers. Western blotting and immunofluorescence analyses were used to further analyze the expression of the epithelial marker E-cadherin and the EMT transcription factor SNAI1.

Co-cultivation with F. nucleatum did not significantly enhance cell viability. The co-cultured cells displayed similarities to the positive control of EMT, exhibiting enhanced migration and expression changes in EMT-related markers. SNAI1 was significantly upregulated, whereas E-cadherin, was significantly downregulated. Notably, resveratrol inhibited F. nucleatum-induced cell migration, decreasing the expression of SNAI1.

Resveratrol inhibited F. nucleatum-induced EMT by downregulating SNAI1, which may provide a target for OSCC treatment.

Patients with inflammatory bowel disease (IBD) who experience long-term chronic inflammation of the colon are at an increased risk of developing colorectal cancer (CRC). Mitotic spindle positioning (MISP), an actin-binding protein, plays a role in mitosis and spindle positioning. MISP is found on the apical membrane of the intestinal mucosa and helps stabilize and elongate microvilli, offering protection against colitis. This study explored the role of MISP in colorectal tumorigenesis using a database, human CRC cells, and a mouse model for colitis-induced colorectal tumors triggered by azoxymethane (AOM)/dextran sodium sulfate (DSS) treatment. We found that MISP was highly expressed in colon cancer patient tissues and that reduced MISP expression inhibited cell proliferation. Notably, MISP-deficient mice showed reduced colon tumor formation in the AOM/DSS-induced colitis model. Furthermore, MISP was found to form a complex with Opa interacting protein 5 (OIP5) in the cytoplasm, influencing the expression of OIP5 in a unidirectional manner. We also observed that MISP increased the levels of phosphorylated STAT3 in the JAK2-STAT3 signaling pathway, which is linked to tumorigenesis. These findings indicate that MISP could be a risk factor for CRC, and targeting MISP might provide insights into the mechanisms of colitis-induced colorectal tumorigenesis.

With the increasing incidence of oral cancer in the world, it has become a hotspot to explore the pathogenesis and prevention of oral cancer. It has been proved there is a strong link between periodontal pathogens and oral cancer. However, the specific molecular and cellular pathogenic mechanisms remain to be further elucidated. Emerging evidence suggests that periodontal pathogens-induced epithelial-mesenchymal transition (EMT) is closely related to the progression of oral cancer. Cells undergoing EMT showed increased motility, aggressiveness and stemness, which provide a pro-tumour environment and promote malignant metastasis of oral cancer. Plenty of studies proposed periodontal pathogens promote carcinogenesis via EMT. In the current review, we discussed the association between the development of oral cancer and periodontal pathogens, and summarized various mechanisms of EMT caused by periodontal pathogens, which are supposed to play an important role in oral cancer, to provide targets for future research in the fight against oral cancer.

Patients suffering from inflammatory bowel disease (IBD) face a two to three-fold higher risk of developing colorectal cancer (CRC) compared to the general population. In recent years, significant progress has been made in comprehending the natural history of IBD-associated CRC (IBD-CRC) and refining its treatment strategies. The decreased incidence of IBD-CRC can be attributed to improved therapeutic management of inflammation, advancements in endoscopy, and early detection of precancerous lesions via surveillance programs. Advanced imaging technologies have made previously undetectable dysplasia visible in most cases, allowing for a much more precise and detailed examination of the mucosa. Additionally, new tools have facilitated the endoscopic resection (ER) of visible lesions in IBD. Particularly, the key to effectively manage colitis-associated colorectal neoplasia (CAN) is to first identify it and subsequently guarantee a complete ER in order to avoid surgery and opt for continuing surveillance. Advanced ER techniques for CAN include endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and hybrid ESD-EMR (h-ESD). This narrative review aims to consolidate the current literature on IBD-CRC, providing an overview of advanced techniques for ER of CAN in IBD, with a particular emphasis on the impact of ESD on the long-term outcomes of IBD patients.

Colorectal cancer (CRC) is the third most common cancer worldwide. One of the main causes of colorectal cancer is inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). Intestinal epithelial cells (IECs), intestinal mesenchymal cells (IMCs), immune cells, and gut microbiota construct the main body of the colon and maintain colon homeostasis. In the development of colitis and colitis-associated carcinogenesis, the damage, disorder or excessive recruitment of different cells such as IECs, IMCs, immune cells and intestinal microbiota play different roles during these processes. This review aims to discuss the various roles of different cells and the crosstalk of these cells in transforming intestinal inflammation to cancer, which provides new therapeutic methods for chemotherapy, targeted therapy, immunotherapy and microbial therapy.

Colorectal cancer (CRC) is the third most common malignant tumor. Fusobacterium nucleatum (F. nucleatum) is overabundant in CRC and associated with metastasis, but the role of F. nucleatum in CRC cell migration and metastasis has not been fully elucidated.

Differential gene analysis, protein-protein interaction, robust rank aggregation analysis, functional enrichment analysis, and gene set variation analysis were used to figure out the potential vital genes and biological functions affected by F. nucleatum infection. The 16S rDNA sequencing and q-PCR were used to detect the abundance of F. nucleatum in tissues and stools. Then, we assessed the effect of F. nucleatum on CRC cell migration by wound healing and transwell assays, and confirmed the role of Matrix metalloproteinase 7 (MMP7) induced by F. nucleatum in cell migration. Furthermore, we dissected the mechanisms involved in F. nucleatum induced MMP7 expression. We also investigated the MMP7 expression in clinical samples and its correlation with prognosis in CRC patients. Finally, we screened out potential small molecular drugs that targeted MMP7 using the HERB database and molecular docking.

F. nucleatum infection altered the gene expression profile and affected immune response, inflammation, biosynthesis, metabolism, adhesion and motility related biological functions in CRC. F. nucleatum was enriched in CRC and promoted the migration of CRC cell by upregulating MMP7 in vitro. MMP7 expression induced by F. nucleatum infection was mediated by the MAPK(JNK)-AP1 axis. MMP7 was highly expressed in CRC and correlated with CMS4 and poor clinical prognosis. Small molecular drugs such as δ-tocotrienol, 3,4-benzopyrene, tea polyphenols, and gallic catechin served as potential targeted therapeutic drugs for F. nucleatum induced MMP7 in CRC.

Our study showed that F. nucleatum promoted metastasis-related characteristics of CRC cell by upregulating MMP7 via MAPK(JNK)-AP1 axis. F. nucleatum and MMP7 may serve as potential therapeutic targets for repressing CRC advance and metastasis.

Patients with inflammatory bowel disease (IBD) have a high risk for colorectal cancer (CRC). This cancer type, which is strongly associated with chronic inflammation, is called colitis-associated CRC (CAC). Understanding the molecular pathogenesis of CAC is crucial to identify biomarkers necessary for early diagnosis and more effective treatment directions. The accumulation of immune cells and inflammatory factors, which constitute a complex chronic inflammatory environment in the intestinal mucosa, may cause oxidative stress or DNA damage to the epithelial cells, leading to CAC development and progression. An important feature of CAC is genetic instability, which includes chromosome instability, microsatellite instability, hypermethylation, and changes in noncoding RNAs. Furthermore, the intestinal microbiota and metabolites have a great impact on IBD and CAC. By clarifying immune, genetic, intestinal microecology, and other related pathogenesis, CAC may be more predictable and treatable.

A significant correlation is observed between Fusobacterium nucleatum (F. nucleatum) and the evolution of inflammatory bowel disease (IBD). Particularly, FomA, a critical pathogenic element of F. nucleatum, inflicts substantial detriment to human intestinal health. Our research focused on the development of recombinant Lactobacillus plantarum that expresses FomA protein, demonstrating its potential in protecting mice from severe IBD induced by F. nucleatum. To commence, two recombinant strains, namely L. plantarum NC8-pSIP409-pgsA'-FomA and NC8-pSIP409-FnBPA-pgsA'-FomA, were successfully developed. Validation of the results was achieved through flow cytometry, ELISA, and MTT assays. It was observed that recombinant L. plantarum instigated mouse-specific humoral immunity and elicited mucosal and T cell-mediated immune responses. Significantly, it amplified the immune reaction of B cells and CD4+T cells, facilitated the secretion of cytokines such as IgA, IL4, and IL10, and induced lymphocyte proliferation in response to FomA protein stimulation. Finally, we discovered that administering recombinant L. plantarum could protect mice from severe IBD triggered by F. nucleatum, subsequently reducing pathological alterations and inflammatory responses. These empirical findings further the study of an innovative oral recombinant Lactobacillus vaccine.

Colorectal cancer (CRC) is the third most common malignant tumor and one of the deadliest cancers. At molecular level, CRC is a heterogeneous disease that could be divided in four Consensus Molecular Subtypes. Given the differences in the disease due to its anatomical location (proximal and distal colon), another classification should be considered. Here, we review the current knowledge on CRC dichotomic´s behaviour based on two different entities; right and left-sided tumors, their impact on clinical trial data, microbiota spatial composition and the interaction with the nervous system. We discuss recent advances in understanding how the spatial tumor heterogeneity influences the tumor growth, progression, and responses to current therapies.

Gastrointestinal (GI) tumors (cancers of the esophagus, gastric, liver, pancreas, colon, and rectum) contribute to a large number of deaths worldwide. STAT3 is an oncogenic transcription factor that promotes the transcription of genes associated with proliferation, antiapoptosis, survival, and metastasis. STAT3 is overactivated in many human malignancies including GI tumors which accelerates tumor progression, metastasis, and drug resistance. Research in recent years demonstrated that noncoding RNAs (ncRNAs) play a major role in the regulation of many signaling pathways including the STAT3 pathway. The major types of endogenous ncRNAs that are being extensively studied in oncology are microRNAs, long noncoding RNAs, and circular RNAs. These ncRNAs can either be tumor-promoters or tumor-suppressors and each one of them imparts their activity via different mechanisms. The STAT3 pathway is also tightly modulated by ncRNAs. In this article, we have elaborated on the tumor-promoting role of STAT3 signaling in GI tumors. Subsequently, we have comprehensively discussed the oncogenic as well as tumor suppressor functions and mechanism of action of ncRNAs that are known to modulate STAT3 signaling in GI cancers.

Colitis-associated colorectal cancer (CAC) is defined as a specific cluster of colorectal cancers that develop as a result of prolonged colitis in patients with inflammatory bowel disease (IBD). Patients with IBD, including ulcerative colitis and Crohn's disease, are known to have an increased risk of developing CAC. Although the incidence of CAC has significantly decreased over the past few decades, individuals with CAC have increased mortality compared to individuals with sporadic colorectal cancer, and the incidence of CAC increases with duration. Chronic inflammation is generally recognized as a major contributor to the pathogenesis of CAC. CAC has been shown to progress from colitis to dysplasia and finally to carcinoma. Accumulating evidence suggests that multiple immune-mediated pathways, DNA damage pathways, and pathogens are involved in the pathogenesis of CAC. Over the past decade, there has been an increasing effort to develop clinical approaches that could help improve outcomes for CAC patients. Colonoscopic surveillance plays an important role in reducing the risk of advanced and interval cancers. It is generally recommended that CAC patients undergo endoscopic removal or colectomy. This review summarizes the current understanding of CAC, particularly its epidemiology, mechanisms, and management. It focuses on the mechanisms that contribute to the development of CAC, covering advances in genomics, immunology, and the microbiome; presents evidence for management strategies, including endoscopy and colectomy; and discusses new strategies to interfere with the process and development of CAC. These scientific findings will pave the way for the management of CAC in the near future.

Rosa roxburghii Tratt is a traditional Chinese plant that has been used to treat different inflammatory diseases. The purpose of this study was to investigate the mechanism of action of Rosa roxburghii Tratt extract (RRTE) against ulcerative colitis (UC) using network pharmacology and experimental validation. HPLC-Q/Orbitrap MS was used to rapidly identify the substances contained in RRTE after extracting the active components from the fruit. Then, network pharmacology combined with molecular docking was used to explore the critical target and potential mechanism of RRTE against UC using the active ingredients in RRTE as the research object. Data are presented in a visual manner. Finally, the pharmacological effects of RRTE in alleviating UC were further verified using a DSS-induced UC model of NCM460. The results showed that 25 components in RRTE were identified. A total of 250 targets of the active components and 5376 targets associated with UC were collected. Furthermore, a systematic analysis of the Protein-Protein Interaction (PPI) networks suggests that epidermal growth factor receptor (EGFR), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), and serine/threonine kinase 1 (AKT1) are critical targets for RRTE in the treatment of UC. A comprehensive regulatory network analysis showed that RRTE alleviated UC through the EGFR-mediated PI3K/Akt pathway, and molecular docking showed that active components could strongly bind to EGFR, PIK3R1, and AKT1. In addition, RRTE alleviated dextran sulfate sodium salt (DSS)-induced cell injury and significantly decreased the protein expression levels of EGFR, PIK3R1, and p-AKT in NCM460 cells in vitro. Furthermore, RRTE significantly regulated the expression of the apoptosis-related proteins Apoptotic protease-activating factor 1 (Apaf1), cleaved caspase-3, B-cell lymphoma-2 (Bcl2), and Bcl2 associated X protein (Bax). In conclusion, the components of RRTE are complex, and RRTE can relieve UC through the EGFR-mediated PI3K/Akt pathway.

Colo-rectal cancer (CRC) is undoubtedly one of the most severe complications of inflammatory bowel diseases (IBD). While sporadic CRC develops from a typical adenoma-carcinoma sequence, IBD-related CRC follows different and less understood pathways and its pathophysiological mechanisms were not completely elucidated. In contrast to chronic inflammation, which is nowadays a well-recognised drive towards neoplastic transformation in IBD, only recently was gut microbiota demonstrated to interfere with both inflammation processes and immune-mediated anticancer surveillance. Moreover, the role of microbiota appears particularly complex and intriguing when also considering its multifaceted interactions with multiple environmental stimuli, notably chronic pathologies such as diabetes and obesity, lifestyle (diet, smoking) and vitamin intake. In this review, we presented a comprehensive overview on current evidence of the influence of gut microbiota on IBD-related CRC, in particular its mutual interconnections with the environment.

Human colorectal cancer (CRC) is one of the most common malignancies in men and women across the globe, albeit CRC incidence and mortality shows a substantial racial and ethnic disparity, with the highest burden in African American patients. Even with effective screening tools such as colonoscopy and diagnostic detection assays, CRC remains a substantial health burden. In addition, primary tumors located in the proximal (right) or distal (left) sides of the colorectum have been shown to be unique tumor types that require unique treatment schema. Distal metastases in the liver and other organ systems are the major causes of mortality in CRC patients. Characterizing genomic, epigenomic, transcriptomic and proteomic (multi-omics) alterations has led to a better understanding of primary tumor biology, resulting in targeted therapeutic advancements. In this regard, molecular-based CRC subgroups have been developed that show correlations with patient outcomes. Molecular characterization of CRC metastases has highlighted similarities and differences between metastases and primary tumors; however, our understanding as to how to improve patient outcomes based on metastasis biology is lagging and remains a major obstacle to improving CRC patient outcomes. In this review, we will summarize the multi-omics features of primary CRC tumors and their metastases across racial and ethnic groups, the differences in proximal and distal tumor biology, molecular-based CRC subgroups, treatment strategies and challenges for improving patient outcomes.

Colorectal cancer (CRC) is a dangerous form of cancer that affects the gastrointestinal tract. It is a major global health concern, and the aggressive behavior of tumor cells makes it difficult to treat, leading to poor survival rates for patients. One major challenge in treating CRC is the metastasis, or spread, of the cancer, which is a major cause of death. In order to improve the prognosis for patients with CRC, it is necessary to focus on ways to inhibit the cancer's ability to invade and spread. Epithelial-mesenchymal transition (EMT) is a process that is linked to the spread of cancer cells, also known as metastasis. The process transforms epithelial cells into mesenchymal ones, increasing their mobility and ability to invade other tissues. This has been shown to be a key mechanism in the progression of colorectal cancer (CRC), a particularly aggressive form of gastrointestinal cancer. The activation of EMT leads to increases in the spread of CRC cells, and during this process, levels of the protein E-cadherin decrease while levels of N-cadherin and vimentin increase. EMT also contributes to the development of resistance to chemotherapy and radiation therapy in CRC. Non-coding RNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play a role in regulating EMT in CRC, often through their ability to "sponge" microRNAs. Anti-cancer agents have been shown to suppress EMT and reduce the progression and spread of CRC cells. These findings suggest that targeting EMT or related mechanisms may be a promising approach for treating CRC patients in the clinic.

Inflammatory bowel disease (IBD) can progress into colitis-associated colorectal cancer (CAC) through the inflammation-cancer sequence. Although the mechanism of carcinogenesis in IBD has not been fully elucidated, the existing research indicates that CAC may represent a fundamentally different pathogenesis pattern of colorectal cancer. At present, there is no proven safe and effective medication to prevent IBD cancer. In recent years, Chinese medicine extracts and Chinese medicine monomers have been the subject of numerous articles about the prevention and treatment of CAC, but their clinical application is still relatively limited. Traditional Chinese Medicine (TCM) formulas are widely applied in clinical practice. TCM formulas have demonstrated great potential in the prevention and treatment of CAC in recent years, although there is still a lack of review. Our work aimed to summarize the effects and potential mechanisms of TCM formulas for the prevention and treatment of CAC, point out the issues and limitations of the current research, and provide recommendations for the advancement of CAC research in the future. We discovered that TCM formulas regulated many malignant biological processes, such as inflammation-mediated oxidative stress, apoptosis, tumor microenvironment, and intestinal microecology imbalance in CAC, through a review of the articles published in databases such as PubMed, SCOPUS, Web of Science, Embase, and CNKI. Several major signal transduction pathways, including NF-κB, STAT3, Wnt/β-catenin, HIF-1α, and Nrf2, were engaged. TCM formula may be a promising treatment candidate to control the colitis-cancer transformation, however further high-quality research is required.

Gut microbes are widely considered to be closely associated with colorectal cancer (CRC) development. The microbiota is regarded as a potential identifier of CRC, as several studies have found great significant changes in CRC patients' microbiota and metabolic groups. Changes in microbiota, like Fusobacterium nucleatum and Bacteroides fragilis, also alter the metabolic activity of the host, promoting CRC development. In contrast, the metabolome is an intuitive discriminative biomarker as a small molecular bridge to distinguish CRC from healthy individuals due to the direct action of microbes on the host. More diagnostic microbial markers have been found, and the potential discriminatory power of microorganisms in CRC has been investigated through the combined use of biomic genomic metabolomics, bringing new ideas for screening fecal microbial markers. In this paper, we discuss the potential of microorganisms and their metabolites as biomarkers in CRC screening, hoping to provide thoughts and references for non-invasive screening of CRC.

Unambiguous evidence indicates that microbes are closely linked to various human diseases, including cancer. Most prior work investigating the microbiome of breast tissue describes an association between compositional differences of microbial species in benign and malignant tissues, but few studies have examined the relative abundance of microbial communities within human breast tissue at the species level. In this work, a total of 44 breast tissue samples including benign and malignant tissues with adjacent normal breast tissue pairs were collected, and Oxford Nanopore long-read sequencing was employed to assess breast tissue microbial signatures. Nearly 900 bacterial species were detected from the four dominant phyla: Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes. The bacteria with the highest abundance in all breast tissues was Ralstonia pickettii, and its relative abundance increased with decreasing malignancy. We further examined the breast-tissue microbiome composition with different hormone-receptor statuses, and the relative abundance of the genus Pseudomonas increased most significantly in breast tissues. Our study provides a rationale for exploring microbiomes associated with breast carcinogenesis and cancer development. Further large-cohort investigation of the breast microbiome is necessary to characterize a microbial risk signature and develop potential microbial-based prevention therapies.

Although appendectomy may reduce colorectal inflammation in patients with ulcerative colitis (UC), this surgical procedure has been suggested to be associated with an increased risk of colitis-associated cancer (CAC). Our aim was to explore the mechanism underlying the appendectomy-associated increased risk of CAC.

Five-week-old male BALB/c mice underwent appendectomy, appendicitis induction, or sham laparotomy. They were then exposed to azoxymethane/dextran sodium sulfate (AOM/DSS) to induce CAC. Mice were killed 12 weeks later, and colons were taken for pathological analysis and immunohistochemistry (CD3 and CD8 staining). Human colonic tumors from 21 patients with UC who underwent surgical resection for CAC were immunophenotyped and stratified according to appendectomy status.

Whereas appendectomy significantly reduced colitis severity and increased CAC number, appendicitis induction without appendectomy led to opposite results. Intratumor CD3+ and CD8+ T-cell densities were lower after appendectomy and higher after appendicitis induction compared with the sham laparotomy group. Blocking lymphocyte trafficking to the colon with the anti-α4β7 integrin antibody or a sphingosine-1-phosphate receptor agonist suppressed the inducing effect of the appendectomy on tumors' number and on CD3+/CD8+ intratumoral density. CD8+ or CD3+ T cells isolated from inflammatory neo-appendix and intravenously injected into AOM/DSS-treated recipient mice increased CD3+/CD8+ T-cell tumor infiltration and decreased tumor number. In UC patients with a history of appendectomy, intratumor CD3+ and CD8+ T-cell densities were decreased compared with UC patients without history of appendectomy.

In UC, appendectomy could suppress a major site of T-cell priming, resulting in a less efficient CAC immunosurveillance.

Inflammatory bowel disease (IBD) is a chronic non-specific inflammatory disease of intestinal tract and a common digestive system disease. Current studies have shown that IBD significantly increases the incidence of colorectal cancer (CRC), and is positively correlated with the degree and extent of inflammation of IBD. The relationship between IBD and CRC has attracted extensive attention. However, the relationship between IBD and CRC has not been systematically studied by bibliometrics and visual analysis. This study conducted bibliometric analysis based on 3528 publications from the Core Collection of Web of Science to determine the research status, research hotspots and frontiers of this field. The results show that the number of publications has increased significantly over the past 10 years. The cooperative network analysis shows that the United States, Mayo Clin and Bo Shen are the country, institution and author with the most publications respectively. Belgium, Icahn Sch Med Mt Sinai and Erik Mooiweer are the most collaborative country, institution and author respectively. Analysis of keywords and references showed that inflammation, intestinal flora, and obesity were hot topics in this field. Analysis of keyword outbreaks shows that the gut microbiome and metabolism will be an emerging new research area and a potential hot spot for future research. This study is the first to visually examine the association between IBD and CRC using bibliometrics and visual analysis, and to predict potential future research trends.

Colorectal cancer(CRC) is the third most frequent malignant tumor. The gut microbiome acts as a vital component of CRC etiology. Fusobacterium nucleatum(Fn) is a key member of colorectal cancer-associated bacteria. But we lack a systematic and in-depth understanding on its role in CRC evolution. In this article, We reviewed the abundance changes and distribution of Fn in CRC occurrence and development, potential effect of Fn in the initiation of CRC, the source of intratumoral Fn and the cause of its tropism to CRC. In addition, We described the mechanism by which Fn promotes the malignant biological behavior of CRC, affects CRC response to therapy, and shapes the tumor immune microenvironment in great detail. Based on the relationship between Fn and CRC, we proposed strategies for CRC prevention and treatment, and discussed the feasibility and limitations of specific cases, to gain insights into further basic and clinical research in the future.

Microorganisms have long been known to play key roles in the initiation and development of tumors. The oral microbiota and tumorigenesis have been linked in epidemiological research relating to molecular pathology. Notably, some bacteria can impact distal tumors by their gastrointestinal or blood-borne transmission under pathological circumstances. Certain bacteria drive tumorigenesis and progression through direct or indirect immune system actions. This review systemically discusses the recent advances in the field of oral microecology and tumor, including the oncogenic role of oral microbial abnormalities and various potential carcinogenesis mechanisms (excessive inflammatory response, host immunosuppression, anti-apoptotic activity, and carcinogen secretion) to introduce future directions for effective tumor prevention.