Gut microbes play a crucial role in regulating the tumor microenvironment (TME) of colorectal cancer (CRC). Nevertheless, the deep mechanism between the microbiota-TME interaction has not been well explored. In this study, we for the first time discovered that Lactobacillus intestinalis (L. intestinalis) effectively suppressed tumor growth both in the AOM/DSS-induced CRC model and the ApcMin/+ spontaneous adenoma model. Our investigation revealed that L. intestinalis increased the infiltration of immune cells, particularly dendritic cells (DC), in the TME. Mechanically, the tumor-derived CCL5 induced by L. intestinalis recruited DC chemotaxis through the NOD1/NF-κB signaling pathway. In clinical samples and datasets, we found positive correlation between L. intestinalis, CCL5 level, and the DC-related genes. Our study provided a new strategy for microbial intervention for CRC and deepened the understanding of the interaction between tumor cells and the immune microenvironment modulated by gut microbes.

The involvement of Cronobacter, which is frequently associated with meningitis and necrotizing enterocolitis, in human colorectal cancer remains unexplored. In this study, we isolate and characterize a novel strain of C. malonaticus designated PO3 from a fecal sample of a colon cancer patient and demonstrate its proliferative effects on colorectal cancer both in vitro and in vivo. The secretome of PO3 significantly promoted cell proliferation, as evidenced by increased cell viability, fluorescence intensity, and Ki-67 expression, without inducing cell death. Furthermore, using high-resolution mass spectrometry (HRMS), we identified a novel tryptic oncopeptide designated P506, in the PO3 secretome that promotes colorectal cancer. Synthetic P506 further stimulated human colorectal adenocarcinoma cell line HT-29 cell proliferation in a dose-dependent manner. Experiments with the BALB/c mouse model in vivo revealed that both the PO3 secretome and P506 contributed to the development of colorectal polyps and associated histological changes, including dysplasia and altered colonic architecture. These findings suggest that P506, a potent peptide from the PO3 secretome, may have oncogenic potential, promoting colorectal cancer progression.

The antibiotic salinomycin, a well-known cancer stem cell inhibitor, may impact the diversity of the intestinal microbiota in colorectal cancer (CRC) mice, which plays a pivotal role in shaping the immune system. This study explores the anti-cancer effects and mechanisms of combining salinomycin and fecal microbiota transplantation (FMT) in treating CRC.

FMT was given via enema, while salinomycin was injected intraperitoneally into the CRC mouse model induced by azoxymethane/dextran sodium sulfate.

In CRC mice, a large number of LGR5-labeled cancer stem cells and severe disturbances in the intestinal microbiota were observed. Interestingly, salinomycin inhibited the proliferation of cancer stem cells without exacerbating the microbial disorder as expected. In comparison to salinomycin treatment, the combination of salinomycin and FMT significantly improved pathological damage and restored intestinal microbial diversity, which is responsible for shaping the anti-cancer immune microenvironment. The supplementation of FMT significantly increased the levels of propionic acid and butyric acid while also promoting the infiltration of CD8+ T cells and Ly6G+ neutrophils, as well as reducing F4/80+ macrophage recruitment. Notably, cytokines that were not impacted by salinomycin exhibited robust reactions to alterations in the gut microbiota. These included pro-inflammatory factors (IL6, IL12b, IL17, and IL22), chemokine-like protein OPN, and immunosuppressive factor PD-L1.

Salinomycin plays the role of "eliminating pathogenic qi," targeting cancer stem cells; FMT plays the role of "strengthening vital qi," reversing the intestinal microbiota disorder and enhancing anti-cancer immunity. They have a synergistic effect on the development of CRC.

The occurrence and development of colorectal cancer (CRC) is an incredibly long process that involves continuous changes in the tumor microenvironment. These constant changes may ultimately result in genetic alterations and changes in the metabolic processes of some symbiotic bacteria as a way to adapt to the changing environment. Patients with CRC exhibit an altered abundance of Bacteroides fragilis (B. fragilis) as indicated by several studies. To better understand the genomic characteristics and virulence spectrum of B. fragilis strains in tumor tissues, B. fragilis strains were isolated from tumor and paracancerous tissues of CRC patients.

The isolates were identified using 16 S rRNA sequencing, morphological analysis, physiological and biochemical characterization and PCR, and they were then subjected to whole genome sequencing (WGS) analysis.

A strain of B. fragilis enterotoxin (BFT) bft1-producing ZY0302 and a non-enterotoxin-producing B. fragilis ZY0804 were isolated from cancerous and paraneoplastic tissues, respectively. Analysis based on the core and nonessential genes showed that the genomic profiles of the isolates, ZY0302 and ZY0804, differed from those of B. fragilis from other tissue sources. This core and the co-evolution of non-essential genes may be the result of their adaptation to fluctuations in the tumor microenvironment and enhancing their survival. In addition, the ZY0302 and ZY0804 genomes underwent extensive horizontal gene transfer and varying degrees of genomic rearrangements, inversions, insertions, and deletion events, which may favor the enhancement of bacteria's ability to adapt to environmental changes. For instance, the virulence factors, such as the capsular biosynthesis gene clusters and components of the type IV secretion system, acquired through horizontal gene transfer, may facilitated B. fragilis in evading immune responses and managing oxidative stress. Moreover, our analysis revealed that multiple virulence factors identified in the isolates were mainly involved in bacterial adhesion and colonization, oxidative stress, iron acquisition, and immune evasion. This observation is worth noting given that enzymes such as neuraminidase, lipase, hemolysin, protease, and phosphatase, along with genes responsible for LPS biosynthesis, which are recognized for their association with the virulence of B. fragilis, were prevalent among the isolates.

In summary, it is our assertion that the alterations observed in both core and nonessential genes of B. fragilis, which have been isolated from tissues of colorectal cancer patients, along with significant instances of horizontal gene transfer to the genome, are likely intended to enhance adaptation to the evolving conditions of the tumor microenvironment. This study may provide new insights into the interaction between B. fragilis and the CRC microenvironment.

Colorectal liver metastasis (CRLM) represents a major therapeutic challenge in colorectal cancer (CRC), with complex interactions between the gut microbiota and the liver tumor microenvironment (TME) playing a crucial role in disease progression via the gut-liver axis. The gut barrier serves as a gatekeeper, regulating microbial translocation, which influences liver colonization and metastasis. Through the gut-liver axis, the microbiota actively shapes the TME, where specific microbial species and their metabolites exert dual roles in immune modulation. The immunologically "cold" nature of the liver, combined with the influence of the gut microbiota on liver immunity, complicates effective immunotherapy. However, microbiota-targeted interventions present promising strategies to enhance immunotherapy outcomes by modulating the gut-liver axis. Overall, this review highlights the emerging evidence on the role of the gut microbiota in CRLM and provides insights into the molecular mechanisms driving the dynamic interactions within the gut-liver axis.

Colon cancer is a leading cause of cancer-related deaths worldwide and has been increasingly linked to the gut microbiome. Clostridium butyricum (CB), a probiotic, has demonstrated potential in influencing colon cancer cell behavior, particularly through the modulation of long non-coding RNAs (lncRNAs) and mRNAs. This study examines the effects of CB on the expression of lncRNAs and mRNAs in SW480 colon cancer cells and their association with apoptosis. SW480 cells were co-cultured with CB, and total RNA was extracted for microarray analysis to identify differentially expressed lncRNAs and mRNAs. Quantitative real-time PCR and fluorescence staining were utilized to validate the expression changes of selected lncRNAs and to assess markers of apoptosis. Pathway enrichment analysis was performed to explore the biological functions of genes with altered expression. Co-culture with CB resulted in significant changes in lncRNA and mRNA expression, with 50 lncRNAs upregulated and 152 downregulated by more than five-fold. Similarly, 738 mRNAs were upregulated, while 1,088 were downregulated. Apoptosis analysis revealed that CB treatment induced apoptosis in SW480 cells, as evidenced by the upregulation of pro-apoptotic genes such as CASP1, TNF, and BNIP3L, and the downregulation of anti-apoptotic BCL family members. Pathway analysis suggested the involvement of the MAPK signaling pathway, cytokine-cytokine receptor interactions, and other pathways associated with tumor progression. These findings suggest that CB regulates the expression of lncRNAs and mRNAs involved in apoptosis and tumor progression, highlighting their potential as biomarkers and therapeutic targets in colorectal cancer. This study provides a novel therapeutic strategy for colon cancer treatment.

Increasing evidence suggests that the gut microbiome plays a key role in a host of pathological conditions, including cancer. Indeed, the bidirectional communication that occurs between the gut and the brain, known as the 'gut-brain axis,' has recently been implicated in brain tumour pathology. Here, we focus on current research that supports a gut microbiome-brain tumour link with emphasis on high-grade gliomas, the most aggressive of all brain tumours, and the impact on the glioma tumour microenvironment. We discuss the potential use of gut-brain axis signals to improve responses to current and future therapeutic approaches. We highlight that the success of novel treatment strategies may rely on patient-specific microbiome profiles, and these should be considered for personalised treatment approaches.

The holobiome is an interconnected network of microbial ecosystems spanning soil, plants, animals, humans, and the environment. Microbial interactions drive nutrient cycling, pathogen suppression, and climate regulation. Soil microbiomes facilitate carbon sequestration and enhance soil fertility, while marine microbiomes contribute to carbon capture and climate stability. However, industrial agriculture, extensive herbicide use, antibiotic overuse, and climate change threaten microbial diversity, leading to ecosystem and health disruptions. Probiotic interventions help to restore microbial balance. In human health, probiotics support gut microbiota diversity, reduce inflammation, and regulate metabolism. In agriculture, soil probiotics enhance microbial diversity, improve nutrient cycling, and degrade contaminants, increasing crop yields and soil health. Case studies show that microbial inoculants effectively remediate degraded soils and enhance nutrient uptake. Artificial intelligence is transforming microbiome research by enabling predictive modeling, precision probiotic design, and microbial consortia optimization. Interdisciplinary collaboration and supportive policies are essential for restoring microbial equilibria, ensuring ecosystem resilience, and promoting long-term sustainability. The integration of artificial intelligence, clinical research, and sustainable practices is crucial for advancing holobiome science. The holobiome framework underscores the need for interdisciplinary collaboration to address global challenges, bridging environmental sustainability, agriculture, and public health for a resilient future.

In recent years, numerous reports have been published regarding the relationship between the gut microbiota and the tumor immune microenvironment (TIME). However, to date, no systematic study has been conducted on the relationship between gut microbiota and the TIME using bibliometric methods.

To describe the current global research status on the correlation between gut microbiota and the TIME, and to identify the most influential countries, research institutions, researchers, and research hotspots related to this topic.

We searched for all literature related to gut microbiota and TIME published from January 1, 2014, to May 28, 2024, in the Web of Science Core Collection database. We then conducted a bibliometric analysis and created visual maps of the published literature on countries, institutions, authors, keywords, references, etc., using CiteSpace (6.2R6), VOSviewer (1.6.20), and bibliometrics (based on R 4.3.2).

In total, 491 documents were included, with a rapid increase in the number of publications starting in 2019. The country with the highest number of publications was China, followed by the United States. Germany has the highest number of citations in literature. From a centrality perspective, the United States has the highest influence in this field. The institutions with the highest number of publications were Shanghai Jiao Tong University and Zhejiang University. However, the institution with the most citations was the United States National Cancer Institute. Among authors, Professor Giorgio Trinchieri from the National Institutes of Health has the most local impact in this field. The most cited author was Fan XZ. The results of journal publications showed that the top three journals with the highest number of published papers were Frontiers in Immunology, Cancers, and Frontiers in Oncology. The three most frequently used keywords were gut microbiota, tumor microenvironment, and immunotherapy.

This study systematically elaborates on the research progress related to gut microbiota and TIME over the past decade. Research results indicate that the number of publications has rapidly increased since 2019, with research hotspots including "gut microbiota", "tumor microenvironment" and "immunotherapy". Exploring the effects of specific gut microbiota or derived metabolites on the behavior of immune cells in the TIME, regulating the secretion of immune molecules, and influencing immunotherapy are research hotspots and future research directions.

Colorectal cancer (CRC) presents a complex tumor microenvironment influenced by genetic and microbial factors. Microbial DNA from the gut and tumor microenvironment can translocate into the bloodstream, forming a circulating microbiome associated with prognosis and clinicopathological features. This study investigates the peripheral venous blood microbiome in CRC patients using 2bRAD-M sequencing and evaluates its clinical significance.

Peripheral venous blood samples from 29 CRC patients (19 males, 10 females; mean age 57 years) and 10 healthy controls were analyzed to assess microbial diversity. Additionally, 20 tumor tissue samples from CRC patients were examined via RT-qPCR to validate blood-tumor microbial correlations. Statistical analyses evaluated associations between microbial abundance and clinical features, including metastasis and PD-L1 Combined Positive Score (CPS). Comparative analyses between CRC patients and healthy controls were performed to identify disease-specific microbial signatures.

A total of 270 microbial species were identified, with dominant phyla including Actinomycetota, Bacillota, Bacteroidota, and Pseudomonadota. Bosea lupini was significantly associated with metastasis stage (p = 0.034), while Mycobacterium tuberculosis (p = 0.022), Porphyromonas pasteri (p = 0.017), and Bosea lupini (p = 0.045) correlated with CPS. Microbes such as Bosea lupini, Ralstonia mannitolilytica, and Porphyromonas pasteri suggested potential tumor-derived translocation into the bloodstream.

This study identifies a distinct peripheral venous blood microbiome in CRC patients, highlighting specific microbes associated with clinicopathological features and disease progression. These findings suggest the potential of blood microbiomes as noninvasive biomarkers for CRC prognosis and therapeutic targets, warranting further investigation in larger cohorts.

Phage therapy presents a promising solution for combating multidrug-resistant (MDR) bacterial infections and other bacteria-related diseases, attributed to their innate ability to target and lyse bacteria. Recent clinical successes, particularly in treating MDR-related respiratory and post-surgical infections, validated the therapeutic potential of phage therapy. However, the complex microenvironment within the human body poses significant challenges to phage activity and efficacy in vivo. To overcome these barriers, recent advances in phage engineering have aimed to enhance targeting accuracy, improve stability and survivability, and explore synergistic combinations with other therapeutic modalities. This review provides a comprehensive overview of phage therapy, emphasizing the application of engineered phages in antibacterial therapy, tumor therapy, and vaccine development. Furthermore, the review highlights the current challenges and future trends for advancing phage therapy toward broader clinical applications.

Numerous associations have been identified between cancer and the composition and function of the human microbiome. As cancer remains the second leading global cause of mortality, investigating the carcinogenic contributions of microbiome members could advance our understanding of cancer risk and support potential therapeutic interventions. Although fluctuations in bacterial species have been associated with cancer progression, studying their small molecule metabolites offers one avenue to establish support for causal relationships and the molecular mechanisms governing host-microorganism interactions. In this Review, we explore the expanding repertoire of small molecule metabolites and their mechanisms implicated in the risk of developing gastrointestinal cancers.

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.

This article discusses the interplay between colorectal cancer (CRC) stem cells, tumor microenvironment (TME), and gut microbiota, emphasizing their dynamic roles in cancer progression and treatment resistance. It highlights the adaptability of CRC stem cells, the bidirectional influence of TME, and the multifaceted impact of gut microbiota on CRC. The manuscript proposes innovative therapeutic strategies focusing on these interactions, advocating for a shift towards personalized and ecosystem-targeted treatments in CRC. The conclusion underscores the importance of continued research in these areas for developing effective, personalized therapies.

Host microbes are increasingly recognized as key components in various types of cancer, although their exact impact remains unclear. This study investigated the functional significance of Staphylococcus aureus (S. aureus) in breast cancer tumorigenesis and progression. We found that S. aureus invasion resulted in a compromised DNA damage response process, as evidenced by the absence of G1-phase arrest and apoptosis in breast cells in the background of double strand breaks production and the activation of the ataxia-telangiectasia mutated (ATM)-p53 signaling pathway. The high-throughput mRNA sequencing, bioinformatics analysis and pharmacological studies revealed that S. aureus facilitates breast cell metastasis through the innate immune pathway, particularly in cancer cells. During metastasis, S. aureus initially induced the expression of RIG-I-like receptors (RIG-I in normal breast cells, RIG-I and MDA5 in breast cancer cells), which in turn activated NF-κB p65 expression. We further showed that NF-κB p65 activated the CCL5-CCR5 pathway, contributing to breast cell metastasis. Our study provides novel evidence that the innate immune system, triggered by bacterial infection, plays a role in bacterial-driven cancer metastasis.

The gut microbiota has a significant impact on the development and function of intestinal epithelial cells (IECs) by modifying bile acid (BA) metabolites. Recently, specific gut microbiome-derived BAs, such as 7-oxo-deoxycholic acid (7-oxo-DCA) and isodeoxycholic acid (isoDCA), have been identified to be shifted inversely in colitis and hepatic liver diseases. Although the responsible gut microbes have been identified, metabolites' effects on IECs remain largely unclear. We found that although high-fat diet treatment in mice elevated both 7-oxo-DCA and isoDCA levels, during intestinal tumorigenesis, 7-oxo-DCA levels rise while isoDCA levels decrease. Interestingly, 7-oxo-DCA promotes cancer cell growth, while isoDCA suppresses it. Moreover, 7-oxo-DCA promotes whereas isoDCA inhibits the proliferation of intestinal stem cells in organoids derived from WT and APCMin/+ mice, as well as in patient-derived colon cancer organoids. The APCMin/+ mice administered with 7-oxo-DCA heightened gut permeability and increased tumor burden, whereas isoDCA protected gut barrier and reduced tumor loads. Both BAs reshape the BA pool and shifted gut microbiome. Mechanistically, we identified 7-oxo-DCA as a natural antagonist of Farnesoid X Receptor (FXR) to downregulate FXR signaling, as opposed to isoDCA, which is a potent FXR agonist to upregulate FXR signaling. In conclusion, we unveiled the opposing roles of 7-oxo-DCA and isoDCA to promote or inhibit intestinal tumorigenesis, respectively. Manipulating the BA-FXR axis during tumor initiation and progression holds great promise for developing innovative diagnostic and therapeutic approaches for the treatment of colorectal cancer.

The gut microbiome, composed of the colonic microbiota and their host environment, is important for many aspects of human health. A gut microbiome imbalance (gut dysbiosis) is associated with major causes of human morbidity and mortality. Despite the central part our gut microbiome plays in health and disease, mechanisms that maintain homeostasis and properties that demarcate dysbiosis remain largely undefined. Here we discuss that sorting taxa into meaningful ecological units reveals that the availability of respiratory electron acceptors, such as oxygen, in the host environment has a dominant influence on gut microbiome health. During homeostasis, host functions that limit the diffusion of oxygen into the colonic lumen shelter a microbial community dominated by primary fermenters from atmospheric oxygen. In turn, primary fermenters break down unabsorbed nutrients into fermentation products that support host nutrition. This symbiotic relationship is disrupted when host functions that limit the luminal availability of host-derived electron acceptors become weakened. The resulting changes in the host environment drive alterations in the microbiota composition, which feature an elevated abundance of facultatively anaerobic microbes. Thus, the part of the gut microbiome that becomes imbalanced during dysbiosis is the host environment, whereas changes in the microbiota composition are secondary to this underlying cause. This shift in our understanding of dysbiosis provides a novel starting point for therapeutic strategies to restore microbiome health. Such strategies can either target the microbes through metabolism-based editing or strengthen the host functions that control their environment.

Periodontitis has been associated with an increased risk of CRC, as well as a worse prognosis due to increased inflammation mediators and carcinogenic factors. Moreover, direct and indirect virulence factors from periodontal pathogens, such as Fusobacterium nucleatum, could play a pivotal role in malignant transformation and progression. This cross-sectional study aims to evaluate the presence and the stage of periodontitis in a cohort of patients with CRC. The secondary aim is to assess the presence of F. nucleatum and its relationship with patients' general characteristics, concomitant pathologies, tumor characteristics, and drug therapy.

Patients affected by CRC underwent dental examination and periodontal charting with the "North Carolina" probe to assess the presence and stage of periodontitis, according to the new classification of periodontal diseases of the World Workshop of the European Federation of Periodontology (EFP) and the American Academy of Periodontology (AAP) 2017. F. nucleatum presence was assessed by a dorsal tongue swab and related to the patient's general characteristics, concomitant pathologies, tumor characteristics, and drug therapy.

Periodontal disease was found in 94.3% of I/II CRC stage patients and 100% of III/IV CRC stage patients. Severe periodontitis was found in 76% of the advanced CRC stage and 87.9% of patients with initial CRC, while initial periodontitis was found in 12.1% of initial CRC and 24% of late CRC stages, respectively, without significant differences. F. nucleatum presence showed no correlation between the patient's and tumor's characteristics, comorbidities, and drug assumed.

Periodontal disease showed a high prevalence among CRC patients. Moreover, severe periodontitis has a higher prevalence in CRC patients compared to initial periodontitis. F. nucleatum presence was unrelated to CRC stage, site, other comorbidities, and drug therapies. With these data, it is not possible to admit a direct relationship between CRC and periodontal disease, but further case-control studies must be carried out to further prove this aspect. Preventive and operative targeted strategies to maintain a healthy oral status are suggested in CRC patients.

Oral squamous cell carcinoma (OSCC) remains a major death cause in head and neck cancers, but the exact pathogenesis mechanisms of OSCC are largely unclear.

Saliva derived from OSCC patients but not healthy controls (HCs) significantly promotes OSCC development and progression in rat models, and metabolomic analyses reveal saliva of OSCC patients but not HCs and OSCC tissues but not adjacent non-tumor tissues contain higher levels of kynurenic acid (KYNA). Furthermore, large amounts of Streptococcus mutans (S. mutans) colonize in OSCC tumor tissues, and such intratumoral S. mutans mediates KYNA overproductions via utilizing its protein antigen c (PAc). KYNA shifts the cellular types in the tumor microenvironment (TME) of OSCC and predominantly expedites the expansions of S100a8highS100a9high neutrophils to produce more interleukin 1β (IL-1β), which further expands neutrophils and induces CD8 + T cell exhaustion in TME and therefore promotes OSCC. Also, KYNA compromises the therapeutic effects of programmed cell death ligand 1 (PD-L1) and IL-1β blockades in oral carcinogenesis model. Moreover, KYNA-mediated immunosuppressive program and aryl hydrocarbon receptor (AHR) expression correlate with impaired anti-tumor immunity and poorer survival of OSCC patients.

Thus, aberration of oral microbiota and intratumoral colonization of specific oral bacterium such as S. mutans may increase the production of onco-metabolites, exacerbate the oral mucosal carcinogenesis, reprogram a highly immunosuppressive TME, and promote OSCC, highlighting the potential of interfering with oral microbiota and microbial metabolism for OSCC preventions and therapeutics. Video Abstract.

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.

The development and progression of colorectal cancer (CRC) are influenced by the gut environment, much of which is modulated by microbial-derived metabolites. Although some research has been conducted on the gut microbiota, there have been limited empirical investigations on the role of the microbial-derived metabolites in CRC.

In this study, we used LC-MS and 16S rRNA sequencing to identify gut microbiome-associated fecal metabolites in patients with CRC and healthy controls. Moreover, we examined the effects of Faecalibacterium prausnitzii and tyrosol on CRC by establishing orthotopic and subcutaneous tumor mouse models. Additionally, we conducted in vitro experiments to investigate the mechanism through which tyrosol inhibits tumor cell growth.

Our study revealed changes in the gut microbiome and metabolome that are linked to CRC. We observed that Faecalibacterium prausnitzii, a bacterium known for its multiple anti-CRC properties, is significantly more abundant in the intestines of healthy individuals than in those of individuals with CRC. In mouse tumor models, our study illustrated that Faecalibacterium prausnitzii has the ability to inhibit tumor growth by reducing inflammatory responses and enhancing tumor immunity. Additionally, research investigating the relationship between CRC-associated features and microbe-metabolite interactions revealed a correlation between Faecalibacterium prausnitzii and tyrosol, both of which are less abundant in the intestines of tumor patients. Tyrosol demonstrated antitumor activity in vivo and specifically targeted CRC cells without affecting intestinal epithelial cells in cell experiments. Moreover, tyrosol treatment effectively reduced the levels of reactive oxygen species (ROS) and inflammatory cytokines in MC38 cells. Western blot analysis further revealed that tyrosol inhibited the activation of the NF-κB and HIF-1 signaling pathways.

This study investigated the relationship between CRC development and changes in the gut microbiota and microbial-derived metabolites. Specifically, the intestinal metabolite tyrosol exhibits antitumor effects by inhibiting HIF-1α/NF-κB signaling pathway activation, leading to a reduction in the levels of ROS and inflammatory factors. These findings indicate that manipulating the gut microbiota and its metabolites could be a promising approach for preventing and treating CRC and could provide insights for the development of anticancer drugs.

Despite advancements in early detection and treatment in developed countries, colorectal cancer (CRC) remains the third most common malignancy and the second-leading cause of cancer-related deaths worldwide. Conventional chemotherapy, a key option for CRC treatment, has several drawbacks, including poor selectivity and the development of multiple drug resistance, which often lead to severe side effects. In recent years, the use of polysaccharides as drug delivery systems (DDSs) to enhance drug efficacy has gained significant attention. Among these polysaccharides, chitosan (CS), a linear, mucoadhesive polymer, has shown promise in cancer treatment. This review summarizes current research on the potential applications of CS-based hydrogels as DDSs for CRC treatment, with a particular focus on smart hydrogels. These smart CS-based hydrogel systems are categorized into two main types: stimuli-responsive injectable hydrogels that undergo sol-gel transitions in situ, and single-, dual-, and multi-stimuli-responsive CS-based hydrogels capable of releasing drugs in response to various triggers. The review also discusses the structural characteristics of CS, the methods for preparing CS-based hydrogels, and recent scientific advances in smart CS-based hydrogels for CRC treatment.

Predicting associations between microbes and diseases opens up new avenues for developing diagnostic, preventive, and therapeutic strategies. Given that laboratory-based biological tests to verify these associations are often time-consuming and expensive, there is a critical need for innovative computational frameworks to predict new microbe-disease associations. In this work, we introduce a novel prediction algorithm called Predicting Human Disease-Microbe Associations using Cross-Domain Matrix Factorization (CMFHMDA). Initially, we calculate the composite similarity of diseases and the Gaussian interaction profile similarity of microbes. We then apply the Weighted K Nearest Known Neighbors (WKNKN) algorithm to refine the microbe-disease association matrix. Our CMFHMDA model is subsequently developed by integrating the network data of both microbes and diseases to predict potential associations. The key innovations of this method include using the WKNKN algorithm to preprocess missing values in the association matrix and incorporating cross-domain information from microbes and diseases into the CMFHMDA model. To validate CMFHMDA, we employed three different cross-validation techniques to evaluate the model's accuracy. The results indicate that the CMFHMDA model achieved Area Under the Receiver Operating Characteristic Curve scores of 0.9172, 0.8551, and 0.9351$\pm $0.0052 in global Leave-One-Out Cross-Validation (LOOCV), local LOOCV, and five-fold CV, respectively. Furthermore, many predicted associations have been confirmed by published experimental studies, establishing CMFHMDA as an effective tool for predicting potential disease-associated microbes.

The human colonic commensal enterotoxigenic Bacteroides fragilis (ETBF) is associated with chronic colitis and colon cancer. ETBF colonization induces colitis via the Bacteroides fragilis toxin (BFT). BFT secreted by ETBF cause colon inflammation via E-cadherin cleavage/NF-κB signaling. ETBF promotes colon tumorigenesis via interleukin 17A (IL-17A)/CXCL-dependent inflammation, but its bioactive therapeutics in ETBF-promoted tumorigenesis remain unexplored. In the current study, we investigated the caffeic acid phenethyl ester (CAPE) in the murine model of ETBF colitis and tumorigenesis. In this study, we observed that CAPE treatment mitigated inflammation induced by ETBF in mice. Additionally, our findings indicate that CAPE treatment offers protective effects against ETBF-enhanced colon tumorigenesis in a mouse model of colitis-associated colon cancer induced by azoxymethane (AOM) and dextran sulfate sodium. Notably, the decrease in colon tumorigenesis following CAPE administration correlates with a reduction in the expression of IL-17A and CXCL1 in the gastrointestinal tract. The molecular mechanism for CAPE-induced protection against ETBF-mediated tumorigenesis is mediated by IL-17A/CXCL1, and by NF-κB activity in intestinal epithelial cells. Our findings indicate that CAPE may serve as a preventive agent against the development of ETBF-induced colitis and colorectal cancer (CRC).

This research identified the bioactive compounds and antioxidant capacity of the extractable (EP) and non-extractable (NEP) polyphenol fractions of berrycactus (BC). Additionally, the effects of BC and its residue (BCR) on preventing AOM/DSS-induced early colon carcinogenesis were evaluated in vivo. Male Sprague Dawley rats were randomly assigned to six groups (n = 12/group): healthy control (C), AOM/DSS, BC, BCR, BC+AOM/DSS, and BCR+AOM/DSS. NEP was obtained through acid hydrolysis using H2SO4 and HCl (1 M or 4 M). The HCl-NEP fraction exhibited the highest total phenolic and flavonoid content, while condensed tannins were more abundant in the H2SO4-NEP fraction. A total of 33 polyphenols were identified by UPLC-QTOF-MSE in both EP and NEP, some of which were novel to BC. Both NEP hydrolysates demonstrated significant total antioxidant capacity (TEAC), with HCl-NEP exhibiting the highest ORAC values. The BC+AOM/DSS and BCR+AOM/DSS groups exhibited fewer aberrant crypt foci (p < 0.05), reduced colonic epithelial injury, and presented lower fecal β-glucuronidase activity, when compared to AOM/DSS group. No differences in butyric acid concentrations were observed between groups. This study presents novel bioactive compounds in EP and NEP from BC that contribute to chemopreventive effects in early colon carcinogenesis, while reducing fecal β-glucuronidase activity and preserving colonic mucosal integrity.

The human microbiome is a diverse ecosystem of microorganisms that reside in the body and influence various aspects of health and well-being. Recent advances in sequencing technology have brought to light microbial communities in organs and tissues that were previously considered sterile. The gut microbiota plays an important role in host physiology, including metabolic functions and immune modulation. Disruptions in the balance of the microbiome, known as dysbiosis, have been linked to diseases such as cancer, inflammatory bowel disease and metabolic disorders. In addition, the administration of antibiotics can lead to dysbiosis by disrupting the structure and function of the gut microbial community. Targeting strategies are the key to rebalancing the microbiome and fighting disease, including cancer, through interventions such as probiotics, fecal microbiota transplantation (FMT), and bacteria-based therapies. Future research must focus on understanding the complex interactions between diet, the microbiome and cancer in order to optimize personalized interventions. Multidisciplinary collaborations are essential if we are going to translate microbiome research into clinical practice. This will revolutionize approaches to cancer prevention and treatment.

Identifying statistical associations between biological variables is crucial to understanding molecular mechanisms. Most association studies are based on correlation or linear regression analyses, but the identified associations often lack reproducibility and interpretability due to the complexity and variability of omics datasets, making it difficult to translate associations into meaningful biological hypotheses. We developed StableMate, a regression framework, to address these challenges through a process of variable selection across heterogeneous datasets. Given datasets from different environments, such as experimental batches, StableMate selects environment-agnostic (stable) and environment-specific predictors in predicting the response of interest. Stable predictors represent robust functional dependencies with the response, and can be used to build regression models that make generalizable predictions in unseen environments. We applied StableMate to (i) RNA sequencing data of breast cancer to discover genes that consistently predict estrogen receptor expression across disease status; (ii) metagenomics data to identify microbial signatures that show persistent association with colon cancer across study cohorts; and (iii) single-cell RNA sequencing data of glioblastoma to discern signature genes associated with the development of pro-tumour microglia regardless of cell location. Our case studies demonstrate that StableMate is adaptable to regression and classification analyses and achieves comprehensive characterization of biological systems for different omics data types.

Introduction. Disruptions in gut microbiota, known as dysbiosis, have been increasingly linked to pathogenic infections, with Salmonella Typhimurium being a notable contributor to these disturbances.Hypothesis. We hypothesize that the S. Typhimurium 14028 WT strain induces significant dysbiosis in the rat gut microbiota and that the dam and seqA genes play crucial roles in this process.Aim. In this study, it was aimed at investigating the dysbiotic activity of the S. Typhimurium 14028 WT strain on the rat gut microbiota and the roles of dam and seqA genes on this activity.Method. Changes in the rat gut microbiota were determined by examining the anal swap samples taken from the experimental groups of these animals using 16S rRNA high-throughput sequencing technology.Results. In the experimental groups, the dominant phyla were determined to be Firmicutes and Bacteroidetes (P<0.05). However, while the rate of Bacteroidetes was significantly reduced in those treated with the WT and seqA mutants, no significant difference was observed in the dam mutant compared to the control group (P<0.05). In all experimental animals, the dominant species was determined to be Prevotella copri, regardless of the experiment time and application. The analysis results of the samples taken on the third day from the rat groups infected with the S. Typhimurium 14028 WT strain (W2) presented the most striking data of this study.Conclusion. Through distance analysis, we demonstrated that a successful Salmonella infection completely changes the composition of the microbiota, dramatically reduces species diversity and richness in the microbiota and encourages the growth of opportunistic pathogens.

The prevalence of microsporidiosis in the general population, or within specific groups of individuals/patients, is largely underestimated. The absence of specific seroprevalence tools limits knowledge of the epidemiology of these opportunistic pathogens, although known since the 1980s. Since microsporidia hijack the machinery of its host cell and certain species multiply within intestinal cells, a potential link between the parasite and colorectal cancer (CRC) has been suggested.

To explore a potential epidemiological link between microsporidia and CRC, we evaluated the seroprevalence of Encephalitozoon intestinalis among CRC patients and healthy subjects using ELISA assays based on two recombinant proteins, namely rEiPTP1 and rEiSWP1, targeting polar tube and spore wall proteins. ELISA were performed in 141 CRC patients and 135 healthy controls. Patients with CRC had significantly higher anti-rEiPTP1 IgG levels than subjects in the control group. Anti-rEiPTP1 IgG, anti-rEiSWP1 IgG and anti-rEiPTP1 IgA levels were significantly increased among men with CRC compared to healthy men. Women with CRC who had died had higher rEiSWP1 IgG levels than those who were still alive.

These higher antibody levels against microsporidia in patients with CRC suggest a relationship between microsporidia and pathophysiology of CRC.

The gut microbiota influences the effectiveness and side effects of cancer treatments, particularly immunotherapy and associated immune-related complications. This important involvement of the microbiome is supported by the patients receiving antibiotics responding poorly to immunotherapy. Relatively few research has examined the underlying processes, and until recently, data regarding the detection of the microbial organisms that trigger these effects were inconsistent. Since then, a deeper comprehension of the processes of action and taxonomic classification of the relevant species has been attained. It's been demonstrated that certain bacterial species can enhance the body's reaction to immune checkpoint inhibitors through the release of distinct metabolites or products. Nonetheless, in certain patients who are not responding, Gram-negative bacteria may have a dominating suppressive impact. Patients' propensity to react to immunotherapy can be somewhat accurately predicted by machine learning techniques based on their microbiome makeup. Consequently, there has been an increase in interest in modifying the microbiome makeup to enhance patient reaction to medication. Clinical proof-of-concept studies demonstrate that dietary modifications or fecal microbiota transplantation (FMT) might be used therapeutically to increase the efficacy of immunotherapy in cancer patients. Current developments and new approaches for microbiota-based cancer treatments have been emphasized. In conclusion, preclinical research on animals and human clinical trials has made tremendous progress in our understanding of the function of the gut microbiome in health and illness. These investigations have shed light on the effects of food, FMT, probiotics, prebiotics, and microbiome-disease connections. However, there are still a lot of issues and restrictions that must be resolved before this research can be used in real-world clinical settings.

Gastrointestinal (GI) cancers represent a significant global health challenge, driving relentless efforts to identify innovative diagnostic and therapeutic approaches. Recent strides in microbiome research have unveiled a previously underestimated dimension of cancer progression that revolves around the intricate metabolic interplay between GI cancers and the host's gut microbiota. This review aims to provide a comprehensive overview of these emerging metabolic interactions and their potential to catalyze a paradigm shift in precision diagnosis and therapeutic breakthroughs in GI cancers. The article underscores the groundbreaking impact of microbiome research on oncology by delving into the symbiotic connection between host metabolism and the gut microbiota. It offers valuable insights into tailoring treatment strategies to individual patients, thus moving beyond the traditional one-size-fits-all approach. This review also sheds light on novel diagnostic methodologies that could transform the early detection of GI cancers, potentially leading to more favorable patient outcomes. In conclusion, exploring the metabolic interactions between host gut microbiota and GI cancers showcases a promising frontier in the ongoing battle against these formidable diseases. By comprehending and harnessing the microbiome's influence, the future of precision diagnosis and therapeutic innovation for GI cancers appears more optimistic, opening doors to tailored treatments and enhanced diagnostic precision.

The gut microbiota has been recognized as an important determinant in the initiation and progression of colorectal cancer (CRC), with recent studies shining light on the molecular mechanisms that may contribute to the interactions between microbes and the CRC microenvironment. Despite the increasing wealth of associations being established in the field, proving causality remains challenging. Obstacles include the high variability of the microbiome and its context, both across individuals and across time. Additionally, there is a lack of large and representative cohort studies with long-term follow-up and/or appropriate sampling methods for studying the mucosal microbiome. Finally, most studies focus on CRC, whereas interactions between host and bacteria in early events in carcinogenesis remain elusive, reinforced by the heterogeneity of CRC development. Here, we discuss these current most prominent obstacles, the recent developments, and research needs.

Several bacterial taxa enriched in inflammatory bowel diseases and colorectal cancer (CRC) are found in the oral cavity. We conducted a pilot study nested within a six-week aspirin intervention in a randomized placebo-controlled trial to test their response to aspirin intervention. Fifty healthy subjects, 50-75 years old, were randomized to receive 325 mg aspirin (n = 30) or placebo (n = 20) orally once daily for six weeks. Oral tongue swabs were collected at baseline and week six. We estimated the association between aspirin use and the temporal changes in the relative abundance of pre-specified genus level taxa from pre- to post-treatment. The temporal change in relative abundance differed for eight genus level taxa between the aspirin and placebo groups. In the aspirin group, there were significant increases in the relative abundances of Neisseria, Streptococcus, Actinomyces, and Rothia and significant decreases in Prevotella, Veillonella, Fusobacterium, and Porphyromonas relative to placebo. The log ratio of Neisseria to Fusobacterium declined more in the aspirin group than placebo, signaling a potential marker associated with aspirin intervention. These preliminary findings should be validated using metagenomic sequencing and may guide future studies on the role of aspirin on taxa in various oral ecological niches.

Over the past decade, advancements in high-throughput sequencing technologies have led to a qualitative leap in our understanding of the role of the microbiota in human diseases, particularly in oncology. Despite the low biomass of the intratumoral microbiota, it remains a crucial component of the tumor immune microenvironment, displaying significant heterogeneity across different tumor tissues and individual patients. Although immunotherapy has emerged a major strategy for treating tumors, patient responses to these treatments vary widely. Increasing evidence suggests that interactions between the intratumoral microbiota and the immune system can modulate host tumor immune responses, thereby influencing the effectiveness of immunotherapy. Therefore, it is critical to gain a deep understanding of how the intratumoral microbiota shapes and regulates the tumor immune microenvironment. Here, we summarize the latest advancements on the role of the intratumoral microbiota in cancer immunity, exploring the potential mechanisms through which immune functions are influenced by intratumoral microbiota within and outside the gut barrier. We also discuss the impact of the intratumoral microbiota on the response to cancer immunotherapy and its clinical applications, highlighting future research directions and challenges in this field. We anticipate that the valuable insights into the interactions between cancer immunity and the intratumoral microbiota provided in this review will foster the development of microbiota-based tumor therapies.

Colorectal cancer (CRC) is one of the most common cancers worldwide, ranking third in terms of incidence and second as a cause of cancer-related death. There is growing scientific evidence that the gut microbiota plays a key role in the initiation and development of CRC. Specific bacterial species and complex microbial communities contribute directly to CRC pathogenesis by promoting the neoplastic transformation of intestinal epithelial cells or indirectly through their interaction with the host immune system. As a result, a protumoural and immunosuppressive environment is created conducive to CRC development. On the other hand, certain bacteria in the gut microbiota contribute to protection against CRC. In this chapter, we analysed the relationship of the gut microbiota to CRC and the associations identified with specific bacteria. Microbiota plays a key role in CRC through various mechanisms, such as increased intestinal permeability, inflammation and immune system dysregulation, biofilm formation, genotoxin production, virulence factors and oxidative stress. Exploring the interaction between gut microbiota and tumourigenesis is essential for developing innovative therapeutic approaches in the fight against CRC.

The intestinal microbiota and the human body are in a permanent interaction. There is a symbiotic relationship in which the microbiota plays a vitally important role in the performance of numerous functions, including digestion, metabolism, the development of lymphoid tissue, defensive functions, and other processes. It is a true metabolic organ essential for life and has potential involvement in various pathological states, including cancer and pathologies other than those of a digestive nature. A growing topic of great interest for its implications is the relationship between the microbiota and cancer. Dysbiosis plays a role in oncogenesis, tumor progression, and even the response to cancer treatment. The effect of the microbiota on tumor development goes beyond a local effect having a systemic effect. Another aspect of great interest regarding the intestinal microbiota is its relationship with drugs, modifying their activity. There is increasing evidence that the microbiota influences the therapeutic activity and side effects of antineoplastic drugs and also modulates the response of several tumors to antineoplastic therapy through immunological circuits. These data suggest the manipulation of the microbiota as a possible adjuvant to improve oncological treatment. Is it possible to manipulate the microbiota for therapeutic purposes?

: The gut microbiome has emerged as a key player that mechanistically links various risk factors to colorectal cancer (CRC) etiology. However, the role of the gut microbiome in CRC pathogenesis remains unclear. This study aimed to characterize the gut microbiota in healthy controls (HCs) and patients with colorectal adenoma (AD) and CRC in subgroups based on sex and age.

: Study participants who visited the hospital for surveillance of CRC or gastrointestinal symptoms were prospectively enrolled, and the gut microbiome was analyzed based on fecal samples.

: In terms of HC-AD-CRC sequence, commensal bacteria, including lactate-producing (Streptococcus salivarius) and butyrate-producing (Faecalibacterium prausnitzii, Anaerostipes hadrus, and Eubacterium hallii) bacteria, were more abundant in the HC group than in the AD and CRC groups. In the sex comparison, the female HC group had more lactate-producing bacteria (Bifidobacterium adolescentis, Bifidobacterium catenulatum, and Lactobacillus ruminis) than the male HC group. In age comparison, younger subjects had more butyrate-producing bacteria (Agathobaculum butyriciproducens and Blautia faecis) than the older subjects in the HC group. Interestingly, lactate-producing bacteria (B. catenulatum) were more abundant in females than males among younger HC group subjects. However, these sex- and age-dependent differences were not observed in the AD and CRC groups.

: The gut microbiome, specifically lactate- and butyrate-producing bacteria, which were found to be abundant in the HC group, may play a role in preventing the progression of CRC. In particular, lactate-producing bacteria, which were found to be less abundant in healthy male controls may contribute to the higher incidence of CRC in males.

Colon cancer, a prominent contributor to global cancer-related deaths, prompts the need for innovative treatment strategies. Euphorbia resinifera O. Berg (E. resinifera) and Euphorbia officinarum subsp. echinus Hook. f. & Coss Vindt (E. echinus) and their bee-derived products have been integral to traditional Moroccan medicine due to their potential health benefits. These plants have historical use in addressing various health issues, including cancer. However, their effects against colon cancer remain unclear, and the specific mechanisms underlying their anti-cancer effects lack comprehensive investigation.

The study aimed to assess the potential anti-cancer effects of Euphorbia extract on colon cancer cell lines (DLD-1) through various techniques. The apoptosis, migration, and proliferation of DLD-1 cells were measured in DLD-1 cells. In addition, we conducted High-Performance Liquid Chromatography (HPLC) analysis to identify the profile of phenolic compounds present in the studied extracts.

The extracts demonstrated inhibition of colon cancer cell migration. E. resinifera flower and E. echinus stem extracts show significant anti-migratory effects. Regarding anti-proliferative activity, E. resinifera flower extract hindered proliferation, whereas E. echinus flower extract exhibited dose-dependent inhibition. Apoptosis assays revealed E. resinifera flower extract inducing early-stage apoptosis and E. echinus flower extract promoting late-stage apoptosis. While apoptotic protein expression indicated, E. resinifera stem and propolis extracts had minimal impact on apoptosis.

The findings provide evidence supporting the beneficial effects of E resinifera and E. echinus extracts on colon cancer and exerting anti-cancer properties.