The initiation and progression of colorectal cancer (CRC) are intimately associated with genetic, environmental and biological factors. Desulfovibrio vulgaris (DSV), a sulfate-reducing bacterium, has been found excessive growth in CRC patients, suggesting a potential role in carcinogenesis. However, the precise mechanisms underlying this association remain incompletely understood. We have found Desulfovibrio was abundant in high-fat diet-induced Apcmin/+ mice, and DSV, a member of Desulfovibrio, triggered colonocyte proliferation of germ-free mice. Furthermore, the level of DSV progressively rose from healthy individuals to CRC patients. Flagella are important accessory structures of bacteria, which can help them colonize and enhance their invasive ability. We found that D. vulgaris flagellin (DVF) drove the proliferation, migration, and invasion of CRC cells and fostered the growth of CRC xenografts. DVF enriched the epithelial-mesenchymal transition (EMT)-associated genes and characterized the facilitation of DVF on EMT. Mechanistically, DVF induced EMT through a functional transmembrane receptor called leucine-rich repeat containing 19 (LRRC19). DVF interacted with LRRC19 to modulate the ubiquitination of tumor necrosis factor receptor-associated factor (TRAF)6, rather than TRAF2. This interaction drove the ubiquitination of pivotal molecule TAK1, further enhancing its autophosphorylation and ultimately contributing to EMT. Collectively, DVF interacts with LRRC19 to activate the TRAF6/TAK1 signaling pathway, thereby promoting the EMT of CRC. These data shed new light on the role of gut microbiota in CRC and establish a potential clinical therapeutic target.

The focus of this study is to explore the impact of gut microbiota in different states on the blood components of couplet medications (dried toad skin and radix clematidis) and to identify drug metabolites associated with the gut microbiota. By constructing a pseudo-sterile rat model and combining non-targeted metabolomics with plasma pharmacology, we found that the plasma metabolites of couplet medications underwent significant changes in different gut microbiome environments. The GABA and PGE1 levels in the model group and the model+TCM (traditional chinese medicine) group were both significantly lower than those in the normal+TCM group. When the gut microbiota is imbalanced, drug interventions cannot significantly increase the levels of GABA and PGE1. It further confirmed the correlation between the levels of GABA and PGE1 and the gut microbiota. Based on the results of non-targeted metabolomics, we applied network pharmacology and molecular docking to explore the core targets for colorectal cancer treatment based on gut microbiota. In the end, we identified TNF and PPARG as the two core targets. These research findings provide a possibility for clarifying the molecular mechanisms of couplet medications in the treatment of colorectal cancer. It also laid the foundation for further clarifying the molecular mechanisms of Chanling Paste in the treatment of colorectal cancer.

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.

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide and is closely linked to the gut microbiota. Identifying reproducible and generalizable microbial signatures holds significant potential for enhancing early detection and advancing treatment for this deadly disease.

This study integrated various publicly available case-control datasets to identify microbial signatures for CRC. Alpha and beta diversity metrics were evaluated to characterize differences in gut microbial richness, evenness, and overall composition between CRC patients and healthy controls. Differential abundance analysis was conducted using ANCOM-BC and LEfSe to pinpoint individual taxa that were enriched or depleted in CRC patients. Additionally, sccomp, a Bayesian machine learning method from single-cell analysis, was adapted to provide a more robust validation of compositional differences in individual microbial markers.

Gut microbial richness is significantly higher in CRC patients, and overall microbiome composition differs significantly between CRC patients and healthy controls. Several taxa, such as Fusobacterium and Peptostreptococcus, are enriched in CRC patients, while others, including Anaerostipes, are depleted. The microbial signatures identified from the integrated data are reproducible and generalizable, with many aligning with findings from previous studies. Furthermore, the use of sccomp enhanced the precision of individual microbial marker identification.

Biologically, the microbial signatures identified from the integrated data improve our understanding of the gut microbiota's role in CRC pathogenesis and may contribute to the development of translational targets and microbiota-based therapies. Methodologically, this study demonstrates the effectiveness of adapting robust techniques from single-cell research to improve the precision of microbial marker discovery.

Numerous studies demonstrate that intestinal microbiota contribute to colorectal cancer (CRC), which is often associated with dysbiosis. Most of the data were obtained from studies on CRC patients, making it challenging to determine whether alterations in microbiota are a consequence of the pathology or whether they actively drive its progression. Several studies using laboratory animals suggest that gut microbiota may be involved in both the onset and progression of CRC. In the present study we utilized the azoxymethane-dextran sulfate sodium (AOM/DSS) mouse model of CRC to investigate the contribution of healthy-state microbiota to inflammation-associated tumorigenesis. Two cohorts of C57BL/6 mice harboring different intestinal microbiota demonstrated different susceptibility to AOM/DSS treatment. Sequencing of 16S rRNA bacterial DNA from fecal samples revealed Akkermansia muciniphila and Bacteroides acidifaciens as marker features in the healthy-state microbiota (before AOM/DSS administration), which showed a strong positive correlation with tumor incidence. Moreover, the healthy-state abundance of these markers, considered beneficial bacteria, was strongly positively correlated with the sulfate-reducing bacteria Desulfovibrio fairfieldensis identified as a marker of chronic colitis-associated microbiota. Furthermore, the abundances of these marker features, associated with CRC outcome, correlated with the expression of interferon gamma and nitric oxide synthase 2 genes in colon tissue during the early stage of DSS-induced intestinal inflammation. In contrast to multiple studies demonstrating the anti-inflammatory properties of A. muciniphila and B. acidifaciens, our results point out their potential adverse effect under specific conditions of genotoxicity and inflammation in the intestine. Taken together, our findings suggest a complex, context-dependent role of commensal microbiota in inflammation-associated dysbiosis and CRC.

Colorectal cancer (CRC) represents a relevant public health problem, with high incidence and mortality in Western countries. CRC can occur as sporadic (65%-75%), common familial (25%), or as a consequence of an inherited predisposition (up to 10%). While unravelling its genetic basis has been a long trip leading to relevant clinical implementation over more than 30 years, other contributing factors remain to be clarified. Among these, micro-organisms have emerged as critical players in the development and progression of the disease, as well as for CRC treatment response. Fusobacterium nucleatum (Fn) has been associated with CRC development in both pre-clinical models and clinical settings. Fusobacteria are core members of the human oral microbiome, while being less prevalent in the healthy gut, prompting questions about their localization in CRC and its precursor lesions. This review aims to critically discuss the evidence connecting Fn with CRC pathogenesis, its molecular subtypes and clinical outcomes.

Colorectal cancer (CRC) is a prevalent global malignancy with complex etiologies, including microbiota alterations. This study investigates gut microbiota and biofilm-producing bacteria in 35 Thai CRC patients, analyzing paired normal and tumor biopsy samples. Bacterial DNA from the V3-V4 region of 16S rRNA was sequenced, and biofilms were visualized via scanning electron microscopy and fluorescence in situ hybridization (FISH). Results revealed Firmicutes as the dominant phylum, followed by Bacteroidota, Proteobacteria, and Fusobacteriota, with Fusobacteriota and Bacteroidota notably enriched in left-sided CRC. Key biofilm producers-Bacteroides fragilis, Fusobacterium nucleatum, and Pasteurella stomatis-showed significantly higher gene expression in tumor tissues. Dense biofilms and higher Fusobacterium abundance, localized within the crypts of Lieberkuhn, were observed in CRC tissues. These findings highlight CRC-associated microbiota alterations and pathogenic biofilm production, emphasizing a spatial relationship between tumor location and microbial distribution, with potential implications for understanding CRC pathogenesis and therapeutic targeting.

The adverse gut microbiome may underlie the variability in risks of colorectal cancer (CRC) and metachronous CRC in people with Lynch syndrome (LS). The role of pks+/-Escherichia coli (pks+/-E. coli), Enterotoxigenic Bacteroides fragilis (ETBF), and Fusobacterium nucleatum (Fn) in CRCs and adenomas in people with LS is unknown.

A total of 358 LS cases, including 386 CRCs, 90 adenomas, 195 normal colonic mucosa DNA from the Australasian Colon Cancer Family Registry were tested using multiplex TaqMan qPCR. Logistic regression was used to compare the intratumoural prevalence of each bacteria in Lynch CRCs with 1336 sporadic CRCs. Cox proportional-hazards regression estimated the associations of each bacteria with the risk of metachronous CRC and neoplasia.

Pks+ E. coli (odds ratio [95% confidence interval] = 1.60 [1.08-2.35], P = 0.017), pks-E. coli (3.87 [2.58-5.80], P < 0.001) and Fn (19.47 [13.32-28.87], P < 0.001) were significantly enriched in LS CRCs when compared with sporadic CRCs. Pks+ E. coli in the initial CRC was associated with an increased risk of metachronous CRC (hazard ratio [95% confidence interval] = 2.32 [1.29-4.17], P = 0.005) and metachronous colorectal neoplasia (1.51 [1.02-2.23], P = 0.040) when compared with CRCs without pks+ E. coli.

Pks+ E. coli, pks-E. coli, and Fn are enriched within LS CRCs, suggesting possible roles in CRC development in LS. Having intratumoural pks+ E. coli is associated with increased risk of metachronous CRC, suggesting that, if validated, people with LS might benefit from pks+ E. coli screening and eradication.

This work was funded by an NHMRC Investigator grant (GNT1194896) and a Cancer Australia/Cancer Council NSW co-funded grant (GNT2012914).

Microbiome modulation is one of the novel strategies in medicine with the greatest future to improve the health of individuals and reduce the risk of different conditions, including metabolic, immune, inflammatory, and degenerative diseases, as well as cancer. Regarding the latter, many studies have reported the role of the gut microbiome in carcinogenesis, formation and progression of colorectal cancer (CRC), as well as its response to different systemic therapies. Likewise, obesity, one of the most important risk factors for CRC, is also well known for its association with gut dysbiosis. Moreover, obesity and CRC display, apart from microbial dysbiosis, chronic inflammation, which participates in their pathogenesis. Although human and murine studies demonstrate the significant impact of the microbiome in regulating energy metabolism and CRC development, little is understood about the contribution of the microbiome to the development of obesity-associated CRC. Therefore, this systematic review explores the evidence for microbiome changes associated with these conditions and hypothesizes that this may contribute to the pathogenesis of obesity-related CRC. Two databases were searched, and different studies on the relationship among obesity, intestinal microbiota and CRC in clinical and preclinical models were selected. Data extraction was carried out by two reviewers independently, and 101 studies were finally considered. Findings indicate the existence of a risk association between obesity and CRC derived from metabolic, immune, and microbial disorders.

Colorectal cancer (CRC) is one of the most prevalent cancers in terms of diagnosis and mortality. Radiotherapy (RT) remains a mainstay of CRC therapy. As RT relies on DNA damage to promote tumor cell death, the activity of cellular DNA damage repair pathways can modulate cancer sensitivity to therapy. The gut microbiome has been shown to influence intestinal health and is independently associated with CRC development, treatment responses and outcomes. The microbiome can also modulate responses to CRC RT through various mechanisms such as community structure, toxins and metabolites. In this review we explore the use of RT in the treatment of CRC and the molecular factors that influence treatment outcomes. We also discuss how the microbiome can promote radiosensitivity versus radioprotection to modulate RT outcomes in CRC. Understanding the molecular interaction between the microbiome and DNA repair pathways can assist with predicting responses to RT. Once described, these connections between the microbiome and RT response can also be used to identify actionable targets for therapeutic development.

Colorectal cancer (CRC) is a major contributor to global cancer-related mortality with increasing incidence rates in both developed and developing regions. Therefore, CRC presents a significant challenge to global health. The development of innovative tools for enhancing early CRC screening and diagnosis, along with novel treatments and therapies for improved management, remains an urgent necessity. CRC is intricately associated with the gut microbiota, which is integral to food digestion, nutrient generation, drug metabolism, metabolite production, immune enhancement, endocrine regulation, neurogenesis modulation, and the maintenance of physiologic and psychological equilibrium. Dysbiosis or imbalances in the gut microbiome have been implicated in various disorders, including CRC. Emerging evidence highlights the critical role of the gut microbiome in CRC pathogenesis and treatment, which presents potential opportunities for early detection and diagnosis. Despite substantial advances in understanding the relationship between the gut microbiota and CRC, significant challenges persist. Gaining a deeper and more detailed understanding of the interactions between the human microbiota and cancer is essential to fully realize the potential of the microbiota in cancer management. Unlike genetic factors, the gut microbiome is subject to modification, offering a promising avenue for the development of CRC treatments and drug discovery. This review provides an overview of the interactions between the human gut microbiome and CRC, while examining prospects for precision management of CRC.

Colorectal cancer (CRC) is one of the most prevalent forms of cancer globally. The human gut microbiome plays an important role in the development of CRC and serves as a biomarker for early detection and treatment. This research effort focuses on the identification of potential taxonomic biomarkers of CRC using a grouping-based feature selection method. Additionally, this study investigates the effect of incorporating biological domain knowledge into the feature selection process while identifying CRC-associated microorganisms. Conventional feature selection techniques often fail to leverage existing biological knowledge during metagenomic data analysis. To address this gap, we propose taxonomy-based Grouping Scoring Modeling (G-S-M) method that integrates biological domain knowledge into feature grouping and selection. In this study, using metagenomic data related to CRC, classification is performed at three taxonomic levels (genus, family and order). The MetaPhlAn tool is employed to determine the relative abundance values of species in each sample. Comparative performance analyses involve six feature selection methods and four classification algorithms. When experimented on two CRC associated metagenomics datasets, the highest performance metric, yielding an AUC of 0.90, is observed at the genus taxonomic level. At this level, 7 out of top 10 groups (Parvimonas, Peptostreptococcus, Fusobacterium, Gemella, Streptococcus, Porphyromonas and Solobacterium) were commonly identified for both datasets. Moreover, the identified microorganisms at genus, family, and order levels are thoroughly discussed via refering to CRC-related metagenomic literature. This study not only contributes to our understanding of CRC development, but also highlights the applicability of taxonomy-based G-S-M method in tackling various diseases.

Tumor-associated neutrophils (TANs) are important components of the colorectal cancer (CRC) microenvironment. However, their role in CRC remains controversial. This study aimed to assess the prognostic value of TANs in patients with CRC.

We searched the PubMed, EMBASE, and Cochrane Library databases for eligible studies published until January 9, 2023. The pooled hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (95% CI) were calculated with a random-effects model to assess survival outcomes and clinicopathological features. Subgroup analyses were further conducted to identify potential sources of heterogeneity. Funnel plots and Egger's test were used to measure publication bias.

A total of 19 studies with 7721 patients were included in this meta-analysis. The pooled analysis indicated that high peritumoral TAN infiltration in CRC tissue was significantly associated with favorable cancer-specific survival (HR = 0.57; 95% CI: 0.38-0.86; p = 0.007), but not with overall survival or disease-free survival. No association between high intratumoral or unclear compartment TAN infiltration and CRC prognosis was found. Subgroup analyses showed that the association between TANs and the prognosis of CRC patients differed according to antibody types, tumor stage, quantitative methods, and follow-up time. High intratumoral TAN infiltration was significantly associated with histology type, whereas high TAN infiltration in an unclear compartment was significantly associated with gender, tumor location, and the primary tumor site.

High TAN infiltration, especially in the peritumoral compartment, could be a potential prognostic marker in CRC. More high-quality studies are required to explore its specific prognostic value in CRC.

Colorectal cancer (CRC) is the third most common malignancy globally and the second leading cause of cancer-related mortality. Its development is a multifactorial and multistage process influenced by a dynamic interplay between gut microbiota, environmental factors, and fatty acid metabolism. Dysbiosis of intestinal microbiota and abnormalities in microbiota-associated metabolites have been implicated in colorectal carcinogenesis, highlighting the pivotal role of microbial and metabolic interactions. Fatty acid metabolism serves as a critical nexus linking dietary patterns with gut microbial activity, significantly impacting intestinal health. In CRC patients, reduced levels of short-chain fatty acids (SCFAs) and SCFA-producing bacteria have been consistently observed. Supplementation with SCFA-producing probiotics has demonstrated tumor-suppressive effects, while therapeutic strategies aimed at modulating SCFA levels have shown potential in enhancing the efficacy of radiation therapy and immunotherapy in both preclinical and clinical settings. This review explores the intricate relationship between gut microbiota, fatty acid metabolism, and CRC, offering insights into the underlying mechanisms and their potential translational applications. Understanding this interplay could pave the way for novel diagnostic, therapeutic, and preventive strategies in the management of CRC.

Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) can be difficult to diagnose due to the heterogeneity of phenotypes and a lack of validated in vitro tests. This study aimed to provide a better understanding of the course of N-ERD disease, analyze whether there was a delay in clinical diagnosis, and explore the factors that might cause diagnostic delay.

This observational, cross-sectional, study included patients aged over 18. The time taken by clinicians to diagnose N-ERD was recorded as the clinician diagnosis time, while the time taken by patients to complete the N-ERD triad was recorded as the actual diagnosis time. A difference of six months or longer between actual diagnosis and clinician diagnosis times was accepted as diagnostic delay. Statistical analyses were performed to ascertain the parameters that could cause this delay.

The study included a total of 107 patients diagnosed with N-ERD. The patients had been diagnosed with chronic rhinosinusitis with nasal polyps, asthma, and NSAID hypersensitivity for an average duration of 14.9±9.6, 14.3±9.9, and 11.7±9.3 years, respectively. Thirty-nine (36.4%) of the patients had a delayed diagnosis. The mean delay in the diagnosis of N-ERD was 7.4±6.6 (2.0-12.0) years. Delayed diagnosis showed a correlation with thyroid dysfunction (P = 0.021), while it did not have a significant relationship with the remaining factors.

The results of this study have indicated delays in diagnosing N-ERD patients and emphasized the need for adequately recognizing the disease to initiate timely, appropriate treatment.

Colorectal cancer (CRC) is the second most deadly and the third most diagnosed cancer in both sexes worldwide. CRC pathogenesis is associated with risk factors such as genetics, alcohol, smoking, sedentariness, obesity, unbalanced diets, and gut microbiota dysbiosis. The gut microbiota is the microbial community living in symbiosis in the intestine, in a dynamic balance vital for health. Increasing evidence underscores the influence of specific gut microbiota bacterial species on CRC incidence and pathogenesis. In this regard, conjugated linoleic acid (CLA) metabolites produced by certain gut microbiota have demonstrated an anticarcinogenic effect in CRC, influencing pathways for inflammation, proliferation, and apoptosis. CLA production occurs naturally in the rumen, and human bioavailability is through the consumption of food derived from ruminants. In recent years, biotechnological attempts to increase CLA bioavailability in humans have been unfruitful. Therefore, the conversion of essential dietary linoleic acid to CLA metabolite by specific intestinal bacteria has become a promising process. This article reviews the evidence regarding CLA and CLA-producing bacteria as therapeutic agents against CRC and investigates the best strategy for increasing the yield and bioavailability of CLA. Given the potential and limitations of the present strategies, a new microbiome-based precision nutrition approach based on endogenous CLA production by human gut bacteria is proposed. A literature search in the PubMed and PubMed Central databases identified 794 papers on human gut bacteria associated with CLA production. Of these, 51 studies exploring association consistency were selected. After excluding 19 papers, due to health concerns or discrepancies between studies, 32 papers were selected for analysis, encompassing data for 38 CLA-producing bacteria, such as Bifidobacterium and Lactobacillus species. The information was analyzed by a bioinformatics food recommendation system patented by our research group, Phymofood (EP22382095). This paper presents a new microbiome-based precision nutrition approach targeting CLA-producing gut bacterial species to maximize the anticarcinogenic effect of CLA in CRC.

Colorectal cancer (CRC) is the third most prevalent cancer globally and poses a significant health threat, making early detection crucial. This review paper explored emerging detection methods for early screening of CRC, including gut microbiota, metabolites, genetic markers, and artificial intelligence (AI)-based technologies. Current screening methods have their respective advantages and limitations, particularly in detecting precursors. First, the importance of the gut microbiome in CRC progression is discussed, highlighting how specific microbial alterations can serve as biomarkers for early detection, potentially enhancing diagnostic accuracy when combined with traditional screening methods. Next, research on metabolic reprogramming illustrates the relationship between metabolic changes and CRC, with studies developing metabolite-based detection models that show good sensitivity for early diagnosis. In terms of genetic markers, methylated DNA markers like SEPTIN9 have demonstrated high sensitivity, although further validation across diverse populations is necessary. Lastly, AI technology has shown immense potential in improving adenoma detection rates, significantly enhancing the quality of colonoscopic examinations through image recognition techniques. This review aims to provide a comprehensive perspective on new strategies for CRC screening, emphasizing the potential of noninvasive detection technologies and the prospects of AI and genomics in clinical applications. Despite several challenges, this review advocates for future large-scale prospective studies to validate the effectiveness and cost-effectiveness of these new screening methods while promoting the implementation of screening protocols tailored to individual characteristics.

Gut microbes have been used to predict CRC risk. Fecal occult blood test (FOBT) has been recommended for population screening of CRC.

To analyze the effects of fecal occult blood test (FOBT) on gut microbes.

Fecal samples from 107 healthy individuals (FOBT-negative) and 111 CRC patients (39 FOBT-negative and 72 FOBT-positive) were included for 16 S ribosomal RNA sequencing. Based on the results of different FOBT, the community structure and diversity of intestinal bacteria in healthy individuals and CRC patients were analyzed. Characteristic gut bacteria were screened, and various machine learning algorithms were applied to construct CRC risk prediction models.

The gut microbiota of healthy people and CRC patients with different fecal occult blood were mapped. There was no statistical difference in diversity between CRC patients with negative FOBT and positive FOBT. Bacteroides, Blautia and Escherichia-Shigella were more correlated to healthy individuals, while Streptococcus showed higher correlation with CRC patients with negative FOBT. The accuracy of CRC risk prediction model based on the support vector machines (SVM) algorithm was the highest (89.71%). Subsequently, FOBT was included as a characteristic element in the model construction, and the prediction accuracy of the model was all increased. Similarly, the CRC risk prediction model based on SVM algorithm had the highest accuracy (92%).

FOB affects the community composition of gut microbes. When predicting CRC risk based on gut microbiome, considering the influence of FOBT is expected to improve the accuracy of CRC risk prediction.

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.

This editorial, inspired by a recent study published in the World Journal of Gastrointestinal Oncology, covers the research findings on microbiota changes in various diseases. In recurrent colorectal polyps, the abundances of Klebsiella, Parvimonas, and Clostridium increase, while those of Bifidobacterium and Lactobacillus decrease. This dysbiosis may promote the formation and recurrence of polyps. Similar microbial changes have also been observed in colorectal cancer, inflammatory bowel disease, autism spectrum disorder, and metabolic syndrome, indicating the role of increased pathogens and decreased probiotics in these conditions. Regulating the gut microbiota, particularly by increasing probiotic levels, may help prevent polyp recurrence and promote gut health. This microbial intervention strategy holds promise as an adjunctive treatment for patients with colorectal polyps.

Colorectal cancer (CRC) is one of thes most prevalent malignant tumors worldwide. Current therapeutic strategies for CRC have limitations, while nanomaterials show significant potential for diagnosing and treating CRC. This study utilizes bibliometric analysis to evaluate the current status and trends in this field.

Research on nanomaterials in CRC from 2003 to 2024 was retrieved from the Web of Science Core Collection (WOSCC). Tools such as CiteSpace, VOSviewer, RStudio, GraphPad Prism, and Excel were used to analyze trends and hotspots, covering publication trends, countries, institutions, authors, journals, co-citation analysis, and keywords. Visual maps were created to forecast future developments.

The analysis includes 3,683 publications by 17,261 authors from 3,721 institutions across 100 countries/regions, published in 840 journals. Global publications have steadily increased, particularly since 2018. China leads in publication volume and citations, with six of the top ten research institutions and seven of the ten most cited authors, while the United States excels in citation impact and academic centrality. Both countries currently dominate the field, underscoring the urgent need for enhanced international collaboration. Ramezani M and Abnous K lead in publication volume and H-index, while Siegel RL is highly cited. The International Journal of Nanomedicine has the highest publication volume, while the Journal of Controlled Release is the most cited. In addition to "colorectal cancer" and "nanoparticles," the most common keyword is "drug delivery." Emerging research areas such as "metal-organic frameworks (MOFs)" and "green synthesis" are gaining attention as leading hotspots.

This study offers an in-depth analysis of the application of nanomaterials in CRC, promoting interdisciplinary collaboration and advancing scientific progress in this field.

The probiotic gut microbiome and its metabolites are pivotal in regulating host metabolism, inflammation, and immunity. Host genetics, colonization at birth, the host lifestyle, and exposure to diseases and drugs determine microbial composition. Dysbiosis and disruption of homeostasis in the beneficial microbiome have been reported to be involved in the tumorigenesis and progression of colorectal cancer (CRC). However, the influence of bacteria-secreted metabolites on CRC growth is yet to be fully elucidated. In this study, we compared the microbial composition of CRC patients to healthy controls to identify distinct patterns of microbiota-derived metabolites in CRC patients. Metagenomic analysis demonstrated that beneficial bacteria strains; Blautia producta, Bifidobacterium adolescentis, and Bifidobacterium longum decreased, while Parabacteroides distasonis and Bacteroides ovatus were more prevalent in the CRC patient group. Treatment of cancer organoid lines with microbial culture supernatants from Blautia producta, Bifidobacterium adolescentis, and Bifidobacterium longum showed remarkable inhibition of cancer growth. This study demonstrates that the bacterial metabolites depleted in CRC patients may inhibit cancer growth and highlights the effects of microbiome-derived metabolites on CRC growth.

In the last decades, groundbreaking research on the human microbiome has changed our reductionist conception of the etiology and pathogenesis of several chronic diseases. As a result, we have come to appreciate the significance of a balanced microbiome in maintaining human health. In this context, the upper and lower gastrointestinal tracts (GITs) comprise the most abundant and diverse microbiotas of the human body. In addition to its diversity, functional redundancy, and temporal stability, a healthy GIT microbiome is characterized by its body site specificity. In fact, current evidence has indicated that the translocation of oral species to the gut environment through the oral-gut axis is increased in an array of illnesses, including chronic inflammatory and metabolic diseases, neurological disorders, and cancer. Oral pathogens have also been shown to promote gut dysbiosis and systemic inflammation in animal models. Yet, some level of overlapping between oral and gut microbiomes may occur without disruption of these microbial communities and loss of site specificity. The uniqueness of each host-microbiome entity may hinder our ability to define a "universal" normal GIT microbiome. Despite that, this chapter summarizes the predominant health-related taxa along the human GIT, as well as their role in the physiology and immunity of the digestive system. Some mechanisms that may lead to disturbances and relevant shifts in the oral and gut microbiomes of major inflammatory chronic diseases are also pointed out. Lastly, oral-fecal microbial signatures are presented as potential biomarkers for several oral and systemic disorders. The recognition of such symbiotic/dysbiotic microbial profiles may provide insights into the development of more accurate early diagnosis and therapeutic ecological approaches to restore the balance of the GIT microbiome.

The balance between health and disease is intrinsically linked to the interactions between microbial communities and the host. This complex environment of antagonism and synergy involves both prokaryotic and eukaryotic cells, whose collaborative metabolic pathways and immunomodulatory elements influence system homeostasis. As with the gut and other niches, the oral microbiome has the capacity to affect distal host sites. The ability to manipulate this environment holds the potential to impact local and systemic disease.With the increasing threat of antimicrobial resistance, novel approaches to reduce the burden of disease are essential. The use of probiotics and prebiotics is one such strategy. Probiotics introduce non-pathogenic bacteria into the environment to compete with pathogens for nutrients and attachment sites, or to produce metabolites that counteract disease aetiologies. Prebiotic compounds enhance the growth of health-associated organisms, offering additional benefits, whilst a conjunctive approach with probiotics potentially holds even greater promise. Though widely studied in the gastrointestinal context, their potential for treating oral diseases, such as dental caries and periodontitis, is less understood. Additionally, the use of microbial transplantations has demonstrated efficacy in other areas, reducing systemic inflammation and recolonising with commensal bacteria. Here we evaluate their use in the oral context and their modulatory impact on overall health.In this chapter, we discuss how pro- and prebiotic strategies seek to modulate both the oral and gut environments to promote oral health and prevent disease. We assess novel approaches for utilising health-associated microorganisms to combat oral disorders, either administered locally in the mouth or imparting influence through immune modulation via the oral-gut axis. By examining available clinical trial data, we aim to further understand the intricacies involved in this discipline. Furthermore, we consider the challenges facing the research community, including optimal candidate organism/compound selection and colonisation retention, as well as considerations for future research.

Gastric cancer (GC) incidence remains high worldwide, and the survival rate is poor. GC develops from atrophic gastritis (AG), associated with Helicobacter pylori (Hp) infection, passing through intestinal metaplasia and dysplasia steps. Since Hp eradication does not exclude GC development, further investigations are needed. New data suggest the possible role of unexplored gastric microbiota beyond Hp in the progression from AG to GC. Aimed to develop a score that could be used in clinical practice to stratify GC progression risk, here was investigate gastric microbiota in AG Hp-negative patients with or without high-grade dysplasia (HGD) or GC.

Consecutive patients undergoing upper endoscopy within an endoscopic follow-up for AG were considered. The antrum and corpus biopsies were used to assess the microbiota composition along the disease progression by sequencing the 16S ribosomal RNA gene. Statistical differences between HGD/GC and AG patients were included in a multivariate analysis.

HGD/GC patients had a higher percentage of Bacillus in the antrum and a low abundance of Rhizobiales, Weeksellaceae and Veillonella in the corpus. These data were used to calculate a multiparametric score (Resident Gastric Microbiota Dysbiosis Test, RGM-DT) to predict the risk of progression toward HGD/GC. The performance of RGM-DT in discriminating patients with HGD/GC showed a specificity of 88.9%.

The microbiome-based risk prediction model for GC could clarify the role of gastric microbiota as a cancer risk biomarker to be used in clinical practice. The proposed test might be used to personalize follow-up program thanks to a better cancer risk stratification.

The aim of this study was to investigate the biomarkers of salivary and fecal microbiota in Colorectal cancer (CRC). Initially, the study scrutinized the microbial community composition disparities among groups. Utilizing Lasso analysis, it sifted through operational taxonomic units (OTUs) to pinpoint distinctive features. Subsequently, by intersecting feature OTUs across groups, it curated a set of core-shared OTUs and devised a corresponding network. Concluding with functional enrichment analysis, the research delved into the divergent biological functions of these microbial communities within the studied groups. Analysis revealed higher bacterial diversity in saliva compared to feces, with distinct differences at both phylum and genus levels. Feces primarily contained Firmicutes, while saliva was dominated by Bacteroidetes and Proteobacteria. Notably, Escherichia-Shigella and Fusobacterium in feces and Streptococcus in saliva showed increasing abundance from average to adenoma to colorectal cancer. Specific dominant flora was identified within and between groups, including CRC and adenomas across different stages. Seventeen core shared OTUs were identified, and networks of shared OTUs were constructed for each group. Functional enrichment analysis highlighted distinct microbial community functions among the groups. This study's findings on characteristic OTUs in saliva and fecal samples offer valuable insights for distinguishing between healthy individuals, adenoma patients, and those with colorectal cancer. This study identified distinctive OTUs in saliva and feces to distinguish between healthy individuals, adenoma patients, and those with CRC, offering a valuable diagnostic reference.

Various forms of solid tumors harbor intracellular bacteria, but the physiological consequences of these microorganisms are poorly understood. We show that Campylobacter is significantly enriched in primary colorectal cancer (CRC) lesions from patients with metastasis. Campylobacter jejuni-derived cytolethal distending toxin (CDT) promotes CRC metastasis through JAK2-STAT3-MMP9 signaling in liver or pulmonary metastatic mice models, as confirmed in C. jejuni-infected human colonic tissue and CDT-treated colonic tumoroids from patients. Genetic deletion of cdtB (ΔcdtB) or purified CdtB protein demonstrates that the genotoxin is essential for C. jejuni's pro-metastatic property. In C.-jejuni-colonized mice, increased translocation of CDT-producing C. jejuni to extraintestinal implanted tumors potentially leads to accelerated metastasis of these tumors. Overall, these findings demonstrate that an intratumor-bacteria-derived genotoxin accelerates tumor metastasis, potentially opening a new diagnostic and therapeutic avenue for cancer management.

An increasingly important role for gut microbiota in the initiation and progression of colorectal cancer (CRC) has been described. Even in the early stages of transformation, i.e., colorectal adenomas, changes in gut microbiota composition have been observed, and several bacterial species, such as pks+Escherichia coli and enterotoxigenic Bacteroides fragilis, have been proposed to drive colon tumorigenesis. In recent years, several strategies have been developed to study mucosa-associated microbiota (MAM), which is more closely associated with CRC development than lumen-associated microbiota (LAM) derived from fecal samples. This review summarizes the state of the art about the oncogenic actions of gut bacteria and compares the different sampling strategies to collect intestinal microbiota (feces, biopsies, swabs, brushes, and washing aspirates). In particular, this article recapitulates the current knowledge on MAM in colorectal adenomas and serrated polyps, since studying the intestinal microbiota associated with early-stage tumors can elucidate the molecular mechanisms underpinning CRC carcinogenesis.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Increasing scientific evidence supports the idea that gut microbiota dysbiosis accompanies colorectal tumorigenesis, and these changes could be causative. Implementing gut microbiota analysis in clinical practice is limited by sample type, sequencing platform and taxonomic classification. This article aims to address these limitations, providing new insights into the microbiota associated with CRC pathogenesis and implementing its analyses in personalized medicine.

To that aim, we evaluate differences in the bacterial composition of 130 paired tumor and non-tumor adjacent tissues from a cohort of CRC patients from the Biobank of the University of Navarra, Spain. The V3-V4 region of the 16S rRNA gene was amplified, sequenced using the MinION platform, and taxonomically classified using the NCBI database.

To our knowledge, this is the first study to report an increased relative abundance of Streptococcus periodonticum and a decreased relative abundance of Corynebacterium associated with CRC. Genera such as Fusobacterium, Leptotrichia and Streptococcus showed higher relative abundances in tumor than in non-tumor tissues, as previously described in the literature. Specifically, we identified higher levels of Fusobacterium animalis, Fusobacterium nucleatum, Fusobacterium polymorphum and S. periodonticum in tumor tissues. In contrast, genera such as Bacteroides and Corynebacterium showed lower relative abundances in tumor tissues. There were also differences at the taxonomic level between tumor locations.

These results, consistent with previous studies, further support the hypothesis that Leptotrichia and Fusobacterium contribute to CRC progression, with F. nucleatum and F. animalis proposed as key CRC pathogenic taxa. Overall, these results contribute to a better understanding of the CRC-associated microbiota, addressing critical barriers to its implementation in personalized medicine.

As a complicated and heterogeneous condition, breast cancer (BC) has posed a tremendous public health challenge across the world. Recent studies have uncovered the crucial effect of human microbiota on various perspectives of health and disease, which include cancer. The oral-gut microbiome axis, particularly, have been implicated in the occurrence and development of colorectal cancer through their intricate interactions with host immune system and modulation of systemic inflammation. However, the research concerning the impact of oral-gut microbiome axis on BC remains scarce. This study focused on comprehensively reviewing and summarizing the latest ideas about the potential bidirectional relation of the gut with oral microbiota in BC, emphasizing their potential impact on tumorigenesis, treatment response, and overall patient outcomes. This review can reveal the prospect of tumor microecology and propose a novel viewpoint that the oral-gut microbiome axis can be a breakthrough point in future BC studies.

Colorectal cancer (CRC) is one of the deadliest cancers worldwide, mostly arising from adenomatous polyps. Mounting evidence has demonstrated that changes in the gut microbiome play key roles in CRC progression, while quite few studies focused on the altered microbiota architecture of advanced adenoma (AA), a crucial precancerous stage of CRC. Thus, we aimed to investigate the microbial profiles of AA patients.

Fecal samples were collected from 26 AA patients and 26 age- and sex-matched normal controls (NC), and analyzed by shotgun metagenomic sequencing.

Gut microbial dysbiosis was observed in AA patients with lower alpha diversity. Advanced adenoma was characterized by an increased Bacillota/Bacteroidota ratio and higher Pseudomonadota levels compared to normal individuals. Linear discriminant analysis effect size (LEfSe) analysis was performed and identified 14 microbiota with significantly different abundance levels between AA and NC groups. Functional analysis revealed that tryptophan metabolism was upregulated in AA. Correspondingly, the expressions of gut microbes implicated in tryptophan metabolism also changed, including Akkermansia muciniphila, Bacteroides ovatus, Clostridium sporogenes, and Limosilactobacillus reuteri. The microbial network suggested that AA exhibited decreased correlation complexity, with Escherichia coli and Enterobacteriaceae unclassified harboring the strongest connectivity. A diagnostic model consisting of 3 microbial species was established based on random forest, yielding an area under the curve (AUC) of 0.799.

Our study profiled the alterations of the gut microbiome in AA patients, which may enrich the knowledge of microbial signatures along with colorectal tumorigenesis and provide promising biomarkers for AA diagnosis.

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.

Cardiovascular disease (CVD) may be inherited, as recently shown with the identification of single nucleotide polymorphisms (SNPs or "snips") on a 250 kb DNA fragment that encodes 92 proteins associated with CVD. CVD is also triggered by microbial dysbiosis, microbial metabolites, metabolic disorders, and inflammatory intestinal epithelial cells (IECs). The epithelial cellular adhesion molecule (Ep-CAM) and trefoil factor 3 (TFF3) peptide keeps the gut wall intact and healthy. Variations in Ep-CAM levels are directly linked to changes in the gut microbiome. Leptin, plasminogen activator inhibitor 1 (PAI1), and alpha-1 acid glycoprotein 1 (AGP1) are associated with obesity and may be used as biomarkers. Although contactin 1 (CNTN1) is also associated with obesity and adiposity, it regulates the bacterial metabolism of tryptophan (Trp) and thus appetite. A decrease in CNTN1 may serve as an early warning of CVD. Short-chain fatty acids (SCFAs) produced by gut microbiota inhibit pro-inflammatory cytokines and damage vascular integrity. Trimethylamine N-oxide (TMAO), produced by gut microbiota, activates inflammatory Nod-like receptors (NLRs) such as Nod-like receptor protein 3 (NLRP3), which increase platelet formation. Mutations in the elastin gene (ELN) cause supra valvular aortic stenosis (SVAS), defined as the thickening of the arterial wall. Many of the genes expressed by human cells are regulated by gut microbiota. The identification of new molecular markers is crucial for the prevention of CVD and the development of new therapeutic strategies. This review summarizes the causes of CVD and identifies possible CVD markers.

Colorectal cancer (CRC) is highly prevalent, accounting for approximately one-tenth of cancer cases and deaths globally. It stands as the second most deadly and third most common cancer type. Although the gut microbiota has been implicated in CRC carcinogenesis for the last several decades, it remains one of the least understood risk factors for CRC development, as the gut microbiota is highly diverse and variable. Many studies have uncovered unique microbial signatures in CRC patients compared with healthy matched controls, with variations dependent on patient age, disease stage, and location. In addition, mechanistic studies revealed that tumor-associated bacteria produce diverse metabolites, proteins, and macromolecules during tumor development and progression in the colon, which impact both cancer cells and immune cells. Here, we summarize microbiota's role in tumor development and progression, then we discuss how the metabolic alterations in CRC tumor cells, immune cells, and the tumor microenvironment result in the reprogramming of activation, differentiation, functions, and phenotypes of immune cells within the tumor. Tumor-associated microbiota also undergoes metabolic adaptation to survive within the tumor environment, leading to immune evasion, accumulation of mutations, and impairment of immune cells. Finally, we conclude with a discussion on the interplay between gut microbiota, immunometabolism, and CRC, highlighting a complex interaction that influences cancer development, progression, and cancer therapy efficacy.

Infertility is associated with the alteration of the seminal microbiome. However, the onset of dysbiosis remains controversial and the involvement of host factors remains elusive. This study investigates the alterations of the seminal microbiome in male infertility and examines the association and function of DEFB119, a reproductive-tract-specific host antimicrobial peptide, on the seminal microbiome and male fertility. While we observed comparable genera, diversity and evenness of bacterial communities, a marked decrease in the modularity of the metacommunities was observed in patients with abnormal spermiogram (n = 57) as compared to the control (n = 30). A marked elevation of DEFB119 was observed in a subpopulation of male infertile patients (n = 5). Elevated seminal DEFB119 was associated with a decrease in the observed genera, diversity and evenness of bacterial communities, and further distortion of the metacommunities. Mediation analysis suggests the involvement of elevated DEFB119 and dysbiosis of the seminal microbiome in mediating the abnormalities in the spermiogram. Functional experiments showed that recombinant DEFB119 significantly decrease the progressive motility of sperm in patients with abnormal spermiogram. Moreover, DEFB119 demonstrated species-specific antimicrobial activity against common seminal and nonseminal species. Our work identifies an important host factor that mediates the host-microbiome interaction and stratifies the seminal microbiome associated with male infertility. These results may lead to a new diagnostic method for male infertility and regimens for formulating the microbiome in the reproductive tract and other organ systems.

Increasing evidence suggests a significant association between periodontal disease and the occurrence of various cancers. The carcinogenic potential of several periodontal pathogens has been substantiated in vitro and in vivo. This review provides a comprehensive overview of the diverse mechanisms employed by different periodontal pathogens in the development of cancer. These mechanisms induce chronic inflammation, inhibit the host's immune system, activate cell invasion and proliferation, possess anti-apoptotic activity, and produce carcinogenic substances. Elucidating these mechanisms might provide new insights for developing novel approaches for tumor prevention, therapeutic purposes, and survival improvement.

Most sporadic colorectal cancers (CRC) develop through the adenoma-carcinoma sequence. While dysbiosis of the intestinal flora contributes to CRC's pathogenesis, precise microbial taxa closely associated with the colorectal adenoma-carcinoma sequence remain elusive. This meta-analysis aimed to summarize the features of intestinal flora in patients with AD and CRC.

PubMed, Embase, Cochrane Library, and Web of Science were searched for case-control studies comparing the relative abundance of gut microbiota in the feces of patients with AD, CRC, and healthy controls (HC) from inception to January 2024. The weighted mean difference (WMD) with a 95 % confidence interval (CI) was used to display the results. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the entailed literature. Publication bias was evaluated with the Egger's and Begg's tests.

Eleven studies were included, involving 477 CRC patients, 628 AD patients, and 864 healthy controls. Compared with HC, the patients with AD had a significantly lower Chao 1 index (WMD = -30.17, 95 % CI [-41.10, -19.23], P < 0.001) and Shannon index (WMD = -0.11 95 % CI [-0.18, -0.04], P = 0.002). Compared with AD, the CRC patients had a significantly higher Chao1 index (WMD = 22.09, 95 % CI [7.59, 36.00], P = 0.003) and Shannon index (WMD = 0.08, 95 % CI [0.00, 0.15], P = 0.037). Enterobacteriaceae (WMD = 0.03 95 % CI [0.00,0.05], P = 0.047; WMD = 0.02 95 % CI [0.00,0.04], P = 0.027) significantly increased in the order of Control-AD-CRC, while that of Blautia (WMD = -0.00 95 % CI [-0.01, -0.00], P = 0.001; WMD = -0.00 95 % CI [-0.00, -0.00], P = 0.002) was reduced. Compared with HC, the relative abundance of Proteobacteria (WMD = 0.05 95 % CI [0.03,0.07], P < 0.001), Fusobacteria (WMD = 0.02 95 % CI [0.00,0.03], P = 0.042), Streptococcaceae (WMD = 0.03 95 % CI [0.01,0.05], P = 0.017), Prevotellaceae (WMD = 0.02 95 % CI [0.00,0.04], P = 0.040), and Escherichia-Shigella (WMD = 0.06 95 % CI [0.01, 0.11], P = 0.021) was enriched in the CRC group. The relative abundance of Alistipes (WMD = 0.00 95 % CI [0.00,0.01], P = 0.032) and Streptococcus (WMD = 0.00 95 % CI [0.00,0.00], P = 0.001) was increased in the AD vs HC. The relative abundance of Firmicutes (WMD = -0.07 95 % CI [-0.12, -0.03], P = 0.003), Bifidobacteria (WMD = -0.03 95 % CI [-0.05, -0.01], P = 0.016), and Klebsiella (WMD = -0.01 95 % CI [-0.01, -0.00], P = 0.001) was decreased in the CRC vs HC. Compared with AD, the relative abundance of Firmicutes (WMD = -0.04 95 % CI [-0.07, -0.02], P = 0.002), Peptostreptococcaceae (WMD = -0.03 95 % CI [-0.05, -0.00], P = 0.021), Lachnospiraceae (WMD = -0.04 95 % CI [-0.08,-0.00], P = 0.037), Ruminococcaceae (WMD = -0.06 95 % CI [-0.09,-0.03], P < 0.001), Faecalibacterium (WMD = -0.01 95 % CI [-0.02, -0.01], P = 0.001), and Lachnoclostridium (WMD = -0.02 95 % CI [-0.03, -0.00], P = 0.040) was decreased in the CRC group, while Proteobacteria (WMD = 0.04 95 % CI [0.02,0.05], P < 0.001) was increased.

The dysbiosis characterized by reduced levels of short-chain fatty acid (SCFA)-producing bacteria, decreased anti-inflammatory bacteria, increased pro-inflammatory bacteria, and an elevation of bacteria with cytotoxic effects damaging to DNA may represent the specific microbial signature of colorectal adenoma/carcinoma. Further research is required to elucidate the mechanisms by which gut dysbiosis leads to the progression from AD to CRC and to explore the potential of specific microbiota markers in clinical treatment and non-invasive screening.

Fusobacterium nucleatum (F. nucleatum) is one of the key tumorigenic bacteria in colorectal cancer (CRC), yet how F. nucleatum is involved in colorectal cancer carcinogenesis remains unknown.

In the present study, we carried out PathSeq analysis on RNA sequencing data from the 430 primary colon adenocarcinomas in TCGA database to assess the relationship between patients' survival and F. nucleatum abundance. Among patients with cecum and ascending colon tumors, we found that F. nucleatum transcriptome abundance is positively correlated with mutation load. We further demonstrated that patients with both high tumoral abundance of F. nucleatum and high mutation load exhibited poorer survival and DNA damage. We furthermore determined that F. nucleatum-conditioned medium (Fn. CM) induces DNA damage in both in vitro and in vivo studies. In addition, two F. nucleatum-secreted mutagens, namely DL-homocystine and allantoic acid, were identified to lead to DNA damage.

Our finding delineates the genotoxicity of F.nucleatum-secreted mutagens, which provides a basis for further work to investigate the role of F. nucleatum in the pathogenicity of CRC.