Lymphoid tissue-resident commensal bacteria (LRC), a subtype of gut microbiota essential for inflammation-associated carcinogenesis, predominantly attribute to colorectal cancer(CRC), whereas its role was largely unknown. Herein, we found Alcaligenes faecalis (A. faecalis), the main LRC embedded in Peyer's patches, was abundantly enriched in colitis, adenoma, and stage-dependently observed in CRC tissues. Interestingly, A. faecalis alone can not affect intestinal homeostasis, while during colitis, A. faecalis significantly translocated from Peyer's patches to colon, remarkably attenuated immune response abilities of B cells, T cells, and DC cells in PPs, consequently impeded IgA+ B cells homing. Meanwhile, during colitis, the ectopia of A. faecalis in colon tissues, promoted vinculin acetylation by A. faecalis-derived metabolite acetic acid, which impeded intestinal barrier via hindering the binding of vinculin to β-catenin. Our study revealed A. faecalis not only suppress mucosal immune responses via reducing IgA+ B cells in Peyer's patches but also disrupt intestinal barrier via increasing vinculin acetylation, ultimately promoting inflammation-to-cancer transition in CRC.

To study the impact of differing specific pathogen-free gut microbiomes (GMs) on a murine model of inflammatory bowel disease, selected GMs were transferred using embryo transfer (ET), cross-fostering (CF), and co-housing (CH). Prior work showed that the GM transfer method and the microbial composition of donor and recipient GMs can influence microbial colonization and disease phenotypes in dextran sodium sulfate-induced colitis. When a low richness GM was transferred to a recipient with a high richness GM via CH, the donor GM failed to successfully colonize, and a more severe disease phenotype resulted when compared to ET or CF, where colonization was successful. By comparing CH and gastric gavage for fecal material transfer, we isolated the microbial component of this effect and determined that differences in disease severity and survival were associated with microbial factors rather than the transfer method itself. Mice receiving a low richness GM via CH and gastric gavage exhibited greater disease severity and higher expression of pro-inflammatory immune mediators compared to those receiving a high richness GM. This study provides valuable insights into the role of GM composition and colonization in disease modulation.

It has been proven that the microbiome in human bodies can promote or inhibit the treatment effects of the drugs by affecting their toxicities and activities. Therefore, identifying drug-related microbes helps in understanding how drugs exert their functions under the influence of these microbes. Most recent methods for drug-related microbe prediction are developed based on graph learning. However, those methods fail to fully utilize the diverse characteristics of drug and microbe entities from the perspective of a knowledge graph, as well as the contextual relationships among multiple meta-paths from the meta-path perspective. Moreover, previous methods overlook the consistency between the entity features derived from the knowledge graph and the node semantic features extracted from the meta-paths. To address these limitations, we propose a knowledge-graph transformer and node category-sensitive contrastive learning-based drug and microbe association prediction model (KNDM). This model learns the diverse features of drug and microbe entities, encodes the contextual relationships across multiple meta-paths, and integrates the feature consistency. First, we construct a knowledge graph consisting of drug and microbe entities, which aids in revealing similarities and associations between any two entities. Second, considering the heterogeneity of entities in the knowledge graph, we propose an entity category-sensitive transformer to integrate the diversity of multiple entity types and the various relationships among them. Third, multiple meta-paths are constructed to capture and embed the semantic relationships based on similarities and associations among drug and microbe nodes. A meta-path semantic feature learning strategy with recursive gating is proposed to capture specific semantic features of individual meta-paths while fusing contextual relationships among multiple meta-paths. Finally, we develop a node-category-sensitive contrastive learning strategy to enhance the consistency between entity features and node semantic features. Extensive experiments demonstrate that KNDM outperforms eight state-of-the-art drug-microbe association prediction models, while ablation studies validate the effectiveness of its key innovations. Additionally, case studies on candidate microbes associated with three drugs-curcumin, epigallocatechin gallate, and ciprofloxacin-further showcase KNDM's capability to identify potential drug-microbe associations.

5-Fluorouracil (5-FU) is a chemotherapeutic agent that disrupts pyrimidine metabolism, which can interact with gut microbiota, potentially causing dysbiosis and promoting antibiotic resistance. This study analyzed its antimicrobial and antibiofilm effects on Escherichia coli and Enterococcus spp. The Minimum Inhibitory Concentrations (MIC) and Minimum Biofilm Eradication Concentrations (MBEC) of 5-FU were determined against 17 clinical isolates, including resistant and susceptible strains. Biofilm formation and viability were assessed using crystal violet staining and resazurin assays, respectively. Growth curves were generated by exposing selected strains to increasing concentrations of 5-FU and monitoring Optical Density (OD) at 630 nm over 24 hours. Flow cytometry was used to evaluate membrane integrity, using Propidium Iodide (PI), and Reactive Oxygen Species (ROS) production, with DCFH-DA, while Scanning Electron Microscopy (SEM) was used to show the structural alterations in bacterial cells. 5-FU MIC values ranged from 128-512 μM against E. coli and 1-32 μM against Enterococcus spp., with higher MICs observed against resistant strains. MBEC values exceeded planktonic MICs by up to 16-fold for E. coli and 64-fold for Enterococcus spp., ranging from 128 to >2048 μM. At MIC concentrations, membrane damage was increased in both species, while at subinhibitory concentrations, ROS production was exclusively detected in Enterococcus faecalis strains. SEM revealed severe structural alterations, including pore formation, cell shrinkage, cytoplasmic leakage, and cell disintegration highlighting the impact of 5-FU on bacterial morphology. These findings highlight the antibacterial effect of 5-FU, underscoring its potential impact on gut microbial dynamics and the selective pressures it exerts during chemotherapy.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide with limited treatment options for advanced disease stages. Growing evidence implicates the gut microbiota in CRC pathogenesis, prompting interest in probiotics as a potential therapeutic strategy. In this study, we evaluated the effects of two probiotic compositions, CI (a mix of lactobacilli and bifidobacteria) and CII (bifidobacteria alone), in two murine CRC models: the orthotopic MC-38 cecum injection model and the inflammation-driven azoxymethane/dextran sodium sulfate (AOM/DSS) model. CI showed significant anti-tumor effects in the orthotopic model, reducing tumor weight and volume, which was, however, not associated with robust immune activation, suggesting microbiota-driven mechanisms. In contrast, CII was more effective in the AOM/DSS model, reducing colonic inflammation and completely preventing tumor development. Our study demonstrates that probiotics might have great therapeutic potential via modulation of the gut microbiota, and they can exert anti-tumor effects in murine models of CRC with distinct compositions showing differential efficacy depending on the model. CI stabilized the gut microbiome and inhibited pro-tumorigenic taxa in the MC-38 cecum injection model, while CII exhibited anti-inflammatory properties in the AOM/DSS model, highlighting the potential of probiotics as context-specific interventions for CRC. These findings contribute to the growing body of evidence supporting microbiota-targeted strategies in oncology and their relevance for therapeutic applications.

The human microbiome has always been an important determinant of health and recently, its role has also been described in cancer. The altered microbiome could aid cancer progression, modulate chemoresistance and significantly alter drug efficacy. The broad implications of microbes in cancer have prompted researchers to investigate the microbe-cancer axis and identify whether modifying the microbiome could sensitize cancer cells for therapy and improve the survival outcome of cancer patients. The preclinical data has shown that enhancing the number of specific microbial species could restore the patients' response to cancer drugs and the microbial biomarkers may play a vital role in cancer diagnostics. The elucidation of detailed interactions of the human microbiota with cancer would not only help identify the novel drug targets but would also enhance the efficacy of existing drugs. The field exploring the emerging roles of microbiome in cancer is at a nascent stage and an in-depth scientific perspective on this topic would make it more accessible to a wider audience. In this review, we discuss the scientific evidence connecting the human microbiome to the origin and progression of cancer. We also discuss the potential mechanisms by which microbiota affects initiation of cancer, metastasis and chemoresistance. We highlight the significance of the microbiome in therapeutic outcome and evaluate the potential of microbe-based cancer therapy.

Oncogenic KRAS mutations are prevalent in colorectal cancer (CRC) and linked to poor prognosis and therapeutic resistance. Emerging evidence suggests that specific KRAS mutations differentially influence treatment responses. In this study, we generate isogenic Apc-null mouse colon epithelial cells with four common KRAS mutations. Transcriptomic and proteomic analyses reveal significant enrichment of cholesterol and lipid metabolism pathways in KRAS G12V cells, driven by increased SREBP1 expression and mTORC1 activation. Furthermore, KRAS G12V cells exhibit elevated ACSS2 expression and greater dependence on ACSS2 for proliferative advantage compared to other mutants. Inhibition of ACSS2 uniquely sensitizes KRAS G12V cells to MEK inhibition, highlighting a distinct therapeutic vulnerability. Finally, ACSS2 plays a critical role in early KRAS G12V adenoma development, unlike in KRAS G12D adenomas. These findings highlight mutation-specific metabolic reprogramming in KRAS-driven CRC and identify ACSS2 as a potential therapeutic target.

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.

Colorectal cancer (CRC) is ranked as the third most prevalent malignancy and is a leading cause of cancer-related mortality globally, significantly affecting the health and longevity of middle-aged individuals and the elderly. The primary risk factors for CRC are mainly due to unhealthy dietary habits and lifestyle choices, and they have been shown to profoundly influence the composition of the gut microbiota. Given that dietary patterns are critical determinants of gut microbial diversity, a compelling association exists between gut microbiota and the pathogenesis of CRC. Recent research has increasingly focused on the intricate interplay between gut microbiota and CRC, exploring its role in disease initiation, progression, and the modulation of host immune responses. Investigations have demonstrated that certain specific microbial communities can promote inflammation, disrupt metabolic pathways, and produce carcinogenic compounds, thereby contributing to the development of CRC. Conversely, a diverse and balanced gut microbiome may confer protective effects against cancer through mechanisms such as the production of short-chain fatty acids and the enhancement of intestinal barrier integrity. This article provides a comprehensive overview of the characteristics of the gut microbial community and its complex relationship with CRC. It highlights potential mechanisms through which gut microbiota may influence CRC pathogenesis, including chronic inflammation, toxins, metabolites, epigenetic dysregulation, and immune regulatory dysfunction. Additionally, this review summarizes innovative strategies for CRC prevention and treatment, emphasizing the therapeutic potential of probiotics and natural plant extracts. By elucidating these connections, this work aims to enhance the understanding of the gut microbiome's role in CRC.

This study investigated the suppressor effects of carrots depending on cultivation method on AOM/DSS-induced colon cancer in mice by examining cell apoptosis, inflammation response, and metabolites. Carrots grown using different fertilizers significantly suppressed tumor development by modulating cell apoptosis and inflammatory responses in our experimental settings.

Naturaldream Fertilizer Carrot (NFC) cultivated with deep sea water minerals (DSWM) showed effectively increased the expression of apoptosis-related genes and proteins including p53, p21, Bim, Bad, Bax, Bak, Caspase 9, and Caspase 3 in colon tissue, while inhibiting the production of inflammatory factors and related genes and proteins such as TNF-a, IL-1b, IL-6, IFN-g, NF-kB, and iNOS in serum, spleen cells, and liver tissues. Intestinal microbiota analysis revealed a distinct composition in mice receiving carrots compared to the control group, with accumulation of intestinal microorganisms such as Lachnospiraceae, and Mucispirillum schaedleri closely associated with anti-tumor effects.

Overall, our results indicate that carrots, especially carrots grown with DSWM fertilizers, play a crucial role in inhibiting AOM/DSS-induced colon cancer in mice by regulating cell apoptosis and inflammation responses. The present findings provide valuable insights for further exploration of carrots depending on the cultivation method, as a potential dietary source against colon cancer.

Entamoeba histolytica remains a significant cause of global mortality. The involvement of protozoa in microsatellite instability (MSI) and the potential of miRNA-643 as biomarkers for amoebic and colorectal diseases have not been extensively researched. The relationship between the antigenic structure of Entamoeba histolytica Lectin (Eh-lectin) and the altered expression of miRNA-643 and the X-Linked Inhibitor of Apoptosis (XIAP) is still unclear. This study aimed to identify Eh-lectin, miRNA-643, XIAP, and MSI in 150 colorectal cancer biopsy samples using a comprehensive approach that included immunohistochemistry (IHC), Multiplex PCR, RT-qPCR, and Real-Time PCR. To enhance the accuracy of MSI diagnosis, PCR-Multiplex was performed alongside IHC. Among the 150 colorectal cancer biopsy samples analyzed, 39 (comprising 28 MSI-H and 11 MSI-L) showed MSI, while the remaining 111 were MSI-negative. Notably, 11 samples demonstrated a co-occurrence of MSI and Eh-lectin, with increased expression of miRNA-643 relative to XIAP. The presence of MSI in conjunction with Eh-lectin positivity and elevated miRNA-643 expression, along with reduced levels of the XIAP inhibitor gene in colorectal adenocarcinoma biopsy samples, strongly indicates that this protozoan parasite may play a role in the development of MSI by affecting apoptosis.

The intestinal microbiota is a key environmental factor in the development of colorectal cancer (CRC). Here, we report that, in the context of mild colonic inflammation, the microbiota protects against colorectal tumorigenesis in mice. This protection is achieved by microbial suppression of the long non-coding RNA (lncRNA) Snhg9. Snhg9 promotes tumor growth through inhibition of the tumor suppressor p53. Snhg9 suppresses p53 activity by dissociating the p53 deacetylase sirtuin 1 (SIRT1) from the cell cycle and apoptosis regulator 2 (CCAR2). Consequently, the depletion of the microbiota by antibiotics causes upregulation of Snhg9 and accelerates CRC progression. Moreover, Snhg9 is functionally conserved. Human SNHG9 promotes tumor growth via the same mechanism as mouse Snhg9, despite their low sequence similarity.

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

Colon cancer is a leading cause of mortality in Appalachian Kentucky. Studies suggest that the microbiome may influence cancer outcomes. We investigate differential gene expression, the tumor microbiome, and their association as potential drivers of disparities in colon cancer outcomes.

This study analyzed patients diagnosed with colon adenocarcinoma between 2010 and 2023. Demographic data were extracted from Kentucky Cancer Registry. Somatic mutations and significantly mutated genes were identified using Fisher's exact t -test. RNASeq data were processed for gene expression analysis and Holm-Bonferroni method was used to adjust p values for multiple comparisons. The STAR aligner (exotic), v2.1 pipeline, and KrakenUniq database were used to classify microbes in human samples. The R package (exotic) was then used to decontaminate the results.

The final cohort included 2,276 patients, 321 of which had available somatic mutation sequencing data. Demographic differences between Appalachian and non-Appalachian patients included marital status (p = 0.0005), race (p < 0.0001), insurance status (p = 0.0005), BMI (p = 0.001), type 2 diabetes (p < 0.0001), and Charlson Comorbidity Index (p = 0.03). There was no difference in gene mutation frequency. There was differential expression of 228 genes. Differential abundance analysis revealed differences in 381 bacterial species. Importantly, 3 microbiota significantly correlated with survival disparities between Appalachian and non-Appalachian patients: Clostridium cadaveris (adjusted p = 0.009), Ligilactobacillus salivarius (adjusted p = 0.048), and Sutterella wadsworthensis (adjusted p = 0.009).

This is the first report of the distinct tumor microbiome in Appalachian Kentucky and its impact on survival. Further studies are needed to better characterize the unique tumor and gut microbiome of Appalachian patients with colon cancer.

This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.

Probiotics are pivotal in maintaining or restoring the balance of human intestinal microbiota, a crucial factor in mitigating diseases and preserving the host's health. Exploration into Bacteroides spp. reveals substantial promise in their development as next-generation probiotics due to their profound interaction with host immune cells and capability to regulate the microbiome's metabolism by significantly impacting metabolite production. These beneficial bacteria exhibit potential in ameliorating various health issues such as intestinal disorders, cardiovascular diseases, behavioral disorders, and even cancer. Though it's important to note that a high percentage of them are as well opportunistic pathogens, posing risks under certain conditions. Studies highlight their role in modifying immune responses and improving health conditions by regulating lymphocytes, controlling metabolism, and preventing inflammation and cancer. The safety and efficacy of Bacteroides strains are currently under scrutiny by the European Commission for authorization in food processing, marking a significant step towards their commercialization. The recent advancements in bacterial isolation and sequencing methodologies, coupled with the integration of Metagenome-Assembled Genomes (MAGs) binning from metagenomics data, continue to unveil the potential of Bacteroides spp., aiding in the broader understanding and application of these novel probiotics in health and disease management.

Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, necessitating the development of effective preventive strategies. Fenugreek (Trigonella foenum-graecum) possesses well-documented pharmacological properties; however, its chemopreventive potential in colorectal cancer (CRC) remains unexplored. This study evaluates the efficacy of methanolic fenugreek seed extract (FSE) in an azoxymethane (AOM)-induced murine colorectal cancer (CRC) model, focusing on the modulation of oxidative stress, regulation of biomarkers, induction of apoptosis, and maintenance of epithelial integrity. Methods: FSE was extracted using cold maceration (yield: 24%) and analyzed by gas chromatography-mass spectrometry (GC-MS), identifying 13 bioactive compounds, including benzene, 1,3-dimethyl-; 1,3-cyclopentadiene, 5-(1-methylethylidene)-; o-Xylene; benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-; and benzene, 1,2,3-trimethyl-. All 13 compounds identified were matched with the NIST library with high confidence. Molecular docking was used to assess the interactions of FSE bioactives with E-cadherin-β-catenin complexes. Swiss albino mice received an FSE pre-treatment before AOM induction and continued this treatment three times weekly for 21 weeks. Key assessments included survival analysis, body weight changes, serum biomarker levels (GGT, 5'-NT, LDH), antioxidant enzyme activities (SOD, CAT, GPx1, MDA), reactive oxygen species (ROS) quantification, apoptosis detection via flow cytometry, and immunofluorescence-based evaluation of E-cadherin dynamics. Results: FSE improved survival rates, mitigated AOM-induced weight loss, and dose-dependently reduced serum biomarker levels. Antioxidant enzyme activity was restored, while MDA levels declined. A dose-dependent increase in ROS facilitated apoptosis, as confirmed by flow cytometry (16.7% in the low-dose FSE group and 34.5% in the high-dose FSE group). Immunofluorescence studies revealed that FSE-mediated restoration of E-cadherin localization counteracted AOM-induced epithelial disruptions. Conclusions: FSE exhibits potent chemopreventive potential against CRC by modulating oxidative stress, regulating key biomarkers, inducing apoptosis, and restoring epithelial integrity. These findings support further investigations into its clinical relevance for CRC prevention.

This review article aims to address the challenges associated with targeted therapy for the treatment of metastatic colorectal cancer (mCRC). We will first provide an overview of approved targeted therapies for treating mCRC, which include antiangiogenic therapy, as well as inhibitors of EGFR, BRAFV600E, HER2 inhibitors, and immune checkpoints. Second, we discuss the different mechanisms of primary resistance, including tumor heterogeneity, both as inter-patient and intra-patient heterogeneity, and mechanisms of secondary resistance which include: driver oncogene alterations, downstream or parallel bypass signaling, presence of co-dominant driver oncogenes, tumor lineage plasticity, and epithelial to mesenchymal transition. Resistance mechanisms towards the different drug classes targeting mCRC are discussed in detail. Strategies to overcome resistance primarily involve combination of therapies, although this approach is typically linked to increased drug toxicity, manifesting as on and off-target effects. Moreover, the cost and accessibility of targeted therapies pose significant challenges for diverse populations. Addressing these challenges necessitates further research efforts aimed at optimizing the use of targeted therapy in mCRC. Integration of genomic biomarkers, such as sequencing and liquid biopsy, into routine clinical practice holds promise in enhancing treatment outcomes. In conclusion, this comprehensive review underscores the complex challenges encountered in targeted therapy for mCRC.

Glioblastoma (GBM) remains the most aggressive primary brain tumor, with poor survival outcomes and treatment limited to maximal safe surgical resection, chemotherapy with temozolomide, and radiotherapy. While immunotherapy and targeted treatments show promise, therapeutic resistance and disease progression remain major challenges. This is partly due to GBM's classification as a "cold tumor" with low mutational burden and a lack of distinct molecular targets for drug delivery that selectively spare healthy tissue. Emerging evidence highlights the gut microbiota as a key player in cancer biology, influencing both glioma development and treatment response. This review explores the intersectionality between the gut microbiome and GBM, beginning with an overview of microbiota composition and its broader implications in cancer pathophysiology. We then examine how specific microbial populations contribute to glioma oncogenesis, modulating immune responses, inflammation, and metabolic pathways that drive tumor initiation and progression. Additionally, we discuss the gut microbiome's role in glioma therapeutic resistance, including its impact on chemotherapy, radiotherapy, and immunotherapy efficacy. Given its influence on treatment outcomes, we evaluate emerging strategies to modulate gut flora, such as probiotics, dietary interventions, and microbiota-based therapeutics, to enhance therapy response in GBM patients. Finally, we address key challenges and future directions, emphasizing the need for standardized methodologies, mechanistic studies, and clinical trials to validate microbiota-targeted interventions in neuro-oncology. By integrating gut microbiome research into GBM treatment paradigms, we may unlock novel therapeutic avenues to improve patient survival and outcomes.

The gut microbiome comprises a vast community of microbes inhabiting the human alimentary canal, playing a crucial role in various physiological functions. These microbes generally live in harmony with the host; however, when dysbiosis occurs, it can contribute to the pathogenesis of diseases, including osteoporosis. Osteoporosis, a systemic skeletal disease characterized by reduced bone mass and increased fracture risk, has attracted significant research attention concerning the role of gut microbes in its development. Advances in molecular biology have highlighted the influence of gut microbiota on osteoporosis through mechanisms involving immunoregulation, modulation of the gut-brain axis, and regulation of the intestinal barrier and nutrient absorption. These microbes can enhance bone mass by inhibiting osteoclast differentiation, inducing apoptosis, reducing bone resorption, and promoting osteoblast proliferation and maturation. Despite these promising findings, the therapeutic effectiveness of targeting gut microbes in osteoporosis requires further investigation. Notably, gut microbiota has been increasingly studied for their potential in early diagnosis, intervention, and as an adjunct therapy for osteoporosis, suggesting a growing utility in improving bone health. Further research is essential to fully elucidate the therapeutic potential and clinical application of gut microbiome modulation in the management of osteoporosis.

The incidence of colorectal cancer (CRC) has been increasing in recent decades. Current methods for CRC screening have their own drawbacks, thus there is an urgent need to identify the key microbes that drive the development of CRC for wider application in the early detection and prevention of CRC. To address this issue, we performed fecal microbiome analysis by high-throughput sequencing of 16S rRNA gene combined with blood biochemical indicators in patients with CRC stages I, II, III, and IV, healthy people, and patients with polyps. Fecal microbiota of patients with CRC was disturbed, as evidenced by significantly reduced α-diversity in patients with CRC stage IV and markedly different β-diversity. The random forest model identified the top 25 genera from 174 training data, resulting in a diagnostic accuracy of 87.95%. Further, by combining with differential genera analysis, we screened out 11 biomarkers that significantly changed in different groups. Peptostreptococcus, Parvimonas, Shewanella, Oscillibacter, Eggerthella, and Gemella associated with the development of CRC were significantly enriched, while Fenollaria, Staphylococcus, Ezakiella, Finegoldia, and Neisseria associated with the remission of CRC were significantly suppressed in patients with CRC. Importantly, carcinoembryonic antigen (CEA) was significantly correlated with these 11 microbial biomarkers, and carbohydrate antigen 19-9 (CA 19-9) was markedly correlated with Oscillibacter. Notably, co-occurrence network analysis at the genus level exhibited that the microbial co-occurrence network of CRC IV was the most complex and stable. These results suggested that CEA, CA 19-9 and 11 microbial biomarkers may be co-biomarkers for the disease occurrence and development, and non-invasive diagnosis of CRC.

Identifying the key microbes that drive the development of colorectal cancer (CRC) has been important in this field. We delved into the research on the association between CRC and fecal microbiota in this study, providing a detailed analysis of the characteristics of fecal microbiota during the transition from normal intestine to polyps to cancer. Fecal bacterial biomarkers and blood biochemical indicators may be co-biomarkers in the development of CRC.

The aim of this study is to determine which types of microorganisms influence the onset and development of colorectal cancer (CRC) in humans.

In patients with CRC, three swabs were taken for microbiological analysis during surgical removal of the cancer: the first swab from the surface of the healthy intestinal mucosa, the second from the surface of the tumor, and the third from the middle of the tumor tissue.

In the healthy mucosa of the colon, the most prevalent microorganism was Escherichia coli at 70.5%, followed by Enterococcus spp. (47.7%) and Klebsiella/Enterobacter (20.5%). Microbiological analysis of the swabs from the surface of the tumor tissue showed that E. coli was the most prevalent at 72.7%, followed by Enterococcus spp. at 40.9%, Klebsiella/Enterobacter at 25%, and Pseudomonas aeruginosa at 20%. In the center of tumor tissue, E. coli was the most prevalent at 77.3%, followed by Enterococcus spp. at 47.7%, Klebsiella at 27%, and Pseudomonas aeruginosa at 18.2%.

Certain types of bacteria can influence the emergence and development of cancer, while other types can suppress the development of tumor tissue. Microbiological analysis of human stool samples can prevent the development of CRC.

The gut microbiome, specifically enterotoxigenic Bacteroides fragilis (ETBF), has been reported to play a role in colorectal cancer development. We aimed to conduct a systematic review and meta-analysis of published studies to compare the prevalence of ETBF in patients with colorectal cancer and healthy controls as well as in various stages of colorectal cancer.

PubMed, EMBASE, and The Cochrane Library were systematically searched for studies published until May 2024. We utilized studies either comparing the prevalence of ETBF in patients with colorectal cancer and healthy control or examining its prevalence across different stages of colorectal cancer. The prevalence of ETBF colonization in biological samples from individuals with colorectal cancer compared to that in healthy controls or adjacent normal tissue as well as the association between the prevalence of ETBF and various stages of colorectal cancer were plotted using a random-effect or fixed-effect model.

Fourteen relevant articles were identified. Meta-analyses revealed that patients with colorectal cancer had a higher likelihood of having ETBF than healthy controls (odds ratio [OR]: 2.54, 95% confidence interval [CI]: 1.63-3.98, I2 = 55%). Additionally, ETBF detection was lower in stage I/II than in stage III/IV colorectal cancer (OR: 0.61, 95% CI: 0.41-0.91, I2 = 41%).

The prevalence of ETBF was consistently higher in the tissue and fecal samples of patients with colorectal cancer than in those of controls. A difference in ETBF prevalence between stage I/II and stage III/IV colorectal cancer was noted, but further analysis revealed that the conclusion is unreliable.

https://www.crd.york.ac.uk/prospero/, identifier CRD 42024548325.

Colorectal cancer (CRC) poses a significant global health burden, with gut microbiota emerging as a crucial modulator of CRC pathogenesis and therapeutic outcomes. This review synthesizes current evidence on the influence of gut microbiota on tumor immune surveillance and responses to immunotherapies and chemotherapy in CRC. We highlight the role of specific microbial taxa in promoting or inhibiting tumor growth and the potential of microbiota-based biomarkers for predicting treatment efficacy. The review also discusses the implications of microbiota modulation strategies, including diet, probiotics, and fecal microbiota transplantation, for personalized CRC management. By critically evaluating the literature, we aim to provide a comprehensive understanding of the gut microbiota's dual role in CRC and to inform future research directions in this field.

The continuously decreasing cost of next-generation sequencing has recently led to a significant increase in the number of microbiome-related studies, providing invaluable information for understanding host-microbiome interactions and their relation to diseases. A common approach in metagenomics consists of determining the composition of samples in terms of the amount and types of microbial species that populate them, with the goal of identifying microbes whose profiles are able to differentiate samples under different conditions with advanced feature selection techniques. Here, we propose a novel backward variable selection method based on the hyperdimensional computing (HDC) paradigm, which takes inspiration from how the human brain works in the classification of concepts by encoding features into vectors in a high-dimensional space. We validated our method on public metagenomic samples collected from patients affected by colorectal cancer in a case/control scenario, by performing a comparative analysis with other state-of-the-art feature selection methods, obtaining promising results.

Characterizing the microbial composition of metagenomic samples is crucial for identifying potential biomarkers that can distinguish between healthy and diseased states. However, the high dimensionality and complexity of metagenomic data present significant challenges in the context of accurately selecting features. Our backward variable selection method, based on the HDC paradigm, offers a promising approach to overcoming these challenges. By effectively reducing the feature space while preserving essential information, this method enhances the ability to detect critical microbial signatures associated with diseases like colorectal cancer, leading to more precise diagnostic tools.

The association between the oral pathogen Porphyromonas gingivalis (PG) and the gut microbiota in colorectal cancer (CRC) patients has been explored with inconsistent results. This study aims to systematically assess this potential association.

A systematic review was conducted across three databases (Pubmed, Embase and Web of Science) from inception up to January 2023 and updated until November 2024. Inclusion criteria were observational studies examining PG in the microbiota of adults with CRC compared to healthy controls. Exclusion criteria were studies without control group of healthy individuals, other designs or without full-text access. Two reviewers independently selected and extracted data following a pre-registered protocol. Disagreements were resolved by consensus or with a third reviewer. Risk of bias (RoB) was assessed using the Newcastle-Ottawa Scale (NOS). Results were summarized with a flow diagram, tables, and narrative descriptions. Meta-analysis was not feasible, so Fisher's method for combining p-values and the sign test were used as alternative integration methods.

Finally, 18 studies, with 23 analysis units were included, providing a total sample of 4,373 participants (48.0% cases and 52.0%controls), 38.2% men and 61.8% women, with a similar distribution among cases and controls. The mean (SD) age of cases was 63.3 (4.382) years old and 57.0 (7.753) years for controls. Most of the studies analyzed the presence of PG in feces (70.0%) collected before colonoscopy (55.0%) and were classified with good quality (70.0%) in the RoB assessment. Results suggested an effect (Fisher's test, p = .000006) with some evidence towards a positive association of PG in CRC patients compared to healthy controls (Sign test, p = .039).

Results of the systematic review suggest that PG is associated with the microbiota of CRC patients. Lack of information to calculate the effect size prevented the performance of a meta-analysis. Future research should aim for standardized protocols and statistical approaches.

No funding was received for this work.

The research protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 2023 (registration number: CRD42023399382).

Progress in sequencing technology has led to determination of large numbers of protein sequences, and large enzyme databases are now available. Although many computational tools for enzyme annotation were developed, sequence information is unavailable for many enzymes, known as orphan enzymes. These orphan enzymes hinder sequence similarity-based functional annotation, leading gaps in understanding the association between sequences and enzymatic reactions.

Therefore, we developed DeepES, a deep learning-based tool for enzyme screening to identify orphan enzyme genes, focusing on biosynthetic gene clusters and reaction class. DeepES uses protein sequences as inputs and evaluates whether the input genes contain biosynthetic gene clusters of interest by integrating the outputs of the binary classifier for each reaction class. The validation results suggested that DeepES can capture functional similarity between protein sequences, and it can be implemented to explore orphan enzyme genes. By applying DeepES to 4744 metagenome-assembled genomes, we identified candidate genes for 236 orphan enzymes, including those involved in short-chain fatty acid production as a characteristic pathway in human gut bacteria.

DeepES is available at https://github.com/yamada-lab/DeepES. Model weights and the candidate genes are available at Zenodo (https://doi.org/10.5281/zenodo.11123900).

There have been previously reported associations between the gut microbiota, immune cells, and colorectal cancer; however, the specific mechanisms underlying these relationships remain largely unexplored and require further research. Therefore, in this study, we aimed to unravel the interactions between the gut microbiota, immune cells, and colorectal cancer.

The analysis used genome-wide association study (GWAS) data encompassing 207 microbial taxa and 205 functional pathways and data on 731 immune cell phenotypes. Colorectal cancer data on 6 581 cases and 463 421 controls were sourced from the Integrative Epidemiology Unit Open GWAS Project. Univariate inverse-variance weighted Mendelian randomization analysis was used to identify gut microbial taxa associated with colorectal cancer. Mediation analysis was used to identify the mediating role of specific immune cells in the link between gut bacteria and colorectal cancer.

Univariate inverse-variance weighted Mendelian randomization analysis revealed that several microbial taxa from the Actinobacteria and Firmicutes phyla were significantly associated with colorectal cancer. Coriobacteriaceae (odds ratio [OR]: 0.84, 95% confidence interval [CI]: 0.72-0.97), Sutterellaceae (OR: 0.88, 95% CI: 0.78-0.99), Eggerthella (OR: 0.91, 95% CI: 0.84-0.99), Coriobacteriales (OR: 0.84, 95% CI: 0.72-0.97), Collinsella aerofaciens (OR: 0.85, 95% CI: 0.74-0.99), and Ruminococcus bromii (OR: 0.91, 95% CI: 0.83-0.99) were negatively associated with colorectal cancer, whereas Lactobacillales (OR: 1.11, 95% CI: 1.03-1.20), Veillonella (OR: 1.08, 95% CI: 1.01-1.15), and Bifidobacterium bifidum (OR: 1.05, 95% CI: 1.00-1.09) were positively associated with colorectal cancer. Mediation analysis revealed that in the causal pathway from Collinsella aerofaciens to colorectal cancer, CD127 on CD28+ CD45RA- CD8br and human leukocyte antigen (HLA) DR on CD33- HLA DR+, mediated 11.30% and - 6.52% of the effect, respectively, and that in the causal pathway from Ruminococcus bromii to colorectal cancer, IgD- CD38dim %lymphocyte mediated - 14.80% of the effect.

These results highlight the potential of gut microbiota and immune cell phenotypes as novel treatment strategies for colorectal cancer.

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.

Experimental research has uncovered lipocalin 2 (LCN2) as a novel biomarker implicated in the modulation of intestinal inflammation, metabolic homeostasis, and colon carcinogenesis. However, evidence from human research has been scant. We, therefore, explored the association of pre-diagnostic circulating LCN2 concentrations with incident colorectal cancer (CRC) in a nested case-control study within the in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. LCN2 was measured in 1267 incident CRC cases matched to 1267 controls using incidence density sampling. Conditional logistic regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) according to tumor subsite and sex. Weighted Cox proportional hazard regression was used to explore associations by adiposity status. In multivariable-adjusted analyses, the IRR [95% CI] per doubling in LCN2 concentration was 1.16 [0.98-1.37] for CRC overall, 1.26 [1.00-1.59] for colon cancer, and 1.08 [0.85-1.38] for rectal cancer. The association for colon cancer was more pronounced in women (IRR [95% CI], 1.66 [1.20-2.30]) and for proximal colon cancer (IRR [95% CI], 1.96 [1.15-3.34]), whereas no association was seen in men and distal colon cancer. The association for colon cancer was positive in individuals with high waist circumference (hazard ratio [95% CI], 1.69 [1.52-1.88]) and inverse in individuals with low waist circumference (hazard ratio [95% CI], 0.86 [0.76-0.98], P interaction<0.01). Overall, these data suggest that pre-diagnostic LCN2 concentrations were positively associated with colon cancer, particularly occurring in the proximal colon, in women and among individuals with abdominal adiposity.

Colorectal cancer is the third most common malignancy and the fourth leading cause of cancer-related deaths worldwide. Several studies have shown an association between gut microbiota and colorectal cancer. Gut microbiota is unique and can be influenced by geographic factors and habits. This study aimed to determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer.

To determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer in Indonesia.

This case-control study included 59 subjects (35 colorectal cancer patients and 24 non-colorectal cancer patients indicated for colonoscopy at Dr. Cipto Mangunkusumo Gastrointestinal Endoscopy Center and Fatmawati Hospital. Microbiota examination was performed using 16S rRNA sequencing. Bioinformatics analysis was performed using the wf-metagenomics pipeline from EPI2Me-Labs (Oxford Nanopore Technologies platform).

Patients with colorectal cancer had a higher median index value on the Shannon index (3.28 vs 2.82, P > 0.05) and a lower value on the Simpson index (0.050 vs 0.060, P > 0.05). Significant differences in beta diversity were observed at the genus (P = 0.002) and species levels (P = 0.001). Firmicutes, Proteobacteria, Bacteroidetes, and Fusobacteria were the dominant phyla. The genera Bacteroides, Campylobacter, Peptostreptococcus, and Parvimonas were found more frequently in colorectal cancer, while Faecalibacterium, Haemophilus, and Phocaeicola were more frequently found in non-colorectal cancer. The relative abundance of Fusobacterium nucleatum, Bacteroides fragilis, Enterococcus faecalis, Campylobacter hominis, and Enterococcus faecalis species was significantly elevated in patients with colorectal cancer. Meanwhile, Faecalibacterium prausnitzii, Faecalibacterium duncaniae, and Prevotella copri were more commonly found in non-colorectal cancer.

Patients with colorectal cancer exhibit distinct differences in the composition and diversity of their colonic mucosal microbiota compared to those with non-colorectal cancer. This study was reviewed and approved by the Ethics Committee of Faculty of Medicine, Universitas Indonesia (No. KET-1517/UN2.F1/ETIK/PPM.00.02/2023).

Covering: up to 2024.For many years, the value of complex polyketides lay in their medical properties, including their antibiotic and antifungal activities, with little consideration paid to their native functions. However, more recent evidence gathered from the study of inter-organismal interactions has revealed the influence of these metabolites upon the ecological adaptation and distribution of their hosts, as well as their modes of communication. The increasing number of sequenced genomes and associated transcriptomes has also unveiled the widespread occurrence of the underlying biosynthetic enzymes across all kingdoms of life, and the important contributions they make to physiological events specific to each organism. This review depicts the diversity of roles fulfilled by type I polyketides, particularly in light of studies carried out during the last decade, providing an initial overall picture of their diverse functions.

The involvement of nerves in the development of breast cancer has emerged as a significant factor. Interaction between the nervous system and breast cancer can influence tumor initiation, growth, invasion, metastasis, reverse resistance to drugs, promote inflammation in tumors, and impair the immune system's ability to combat cancer. This review examined the intricate relationship linking the nervous system with breast cancer, emphasizing both central and peripheral aspects of the nervous system. Moreover, we reviewed neural cell factors and their impact on breast cancer progression, alongside the interactions between nerves and immunology, microbiota in breast cancer. Furthermore, the study discussed the potential of nerves as biomarkers for diagnosing and prognosticating breast cancer, and evaluated prospects for improving chemotherapy and immunotherapy therapeutic outcomes in breast cancer treatment. We hope to provide a deeper understanding of the neurobiological underpinnings of breast cancer and pave the way for the discovery of innovative therapeutic targets and prognostic markers.

Cannabidiol (CBD) is a non-neurotoxic, phytocannabinoid from cannabis with reported medicinal properties, including antiepileptic and anti-inflammatory activity. Several in vitro and in vivo studies have shown that CBD has antitumor potential against colorectal cancer (CRC), the third deadliest cancer in the world. However, as different mutations influence the antitumor effects and CBD can bind a variety of receptors, it is yet to be determined whether specific CRC mutations affect CBD's efficacy in treatment of CRC. To investigate this, we selected four CRC cell lines, including HCT116, HT-29, LS174T, and LS153, which harbor distinct mutations. Cells were treated with a range of concentrations of CBD to evaluate its cytotoxic effects and impact on cell proliferation, migration, and invasion by using a live-cell imaging system. IC50 values were then calculated for each parameter. The level of endoplasmic reticulum (ER) stress pathway markers was also measured using qRTPCR. The requirements for CB1 or CB2 receptor-medicated signaling were investigated using the selective inhibitors AM251 and SR144528, respectively. Our results demonstrate that CBD induces apoptosis and halts proliferation, migration, and invasion of CRC cell lines in a concentration-dependent manner. CBD showed potent antitumor effects in the tested cell lines with no obvious effect from different mutations such as KRAS, BRAF, APC, PTEN, etc. CBD also induced ER stress in CRC cells but not in healthy intestinal organoids. Cotreatment with SR144528 inhibited the effects of indicating involvement of CB2 receptor activation in the anticancer effects of CBD. Together, these results demonstrated that CBD could be effective for CRC regardless of the underlying mutation through CB2 receptor activation.

Obesity, a global health concern, is associated with severe health issues like type 2 diabetes, heart disease, and respiratory complications. It also increases the risk of various cancers, including melanoma, endometrial, prostate, pancreatic, esophageal adenocarcinoma, colorectal carcinoma, renal adenocarcinoma, and pre-and post-menopausal breast cancer. Obesity-induced cellular changes, such as impaired CD8+ T cell function, dyslipidemia, hypercholesterolemia, insulin resistance, mild hyperglycemia, and fluctuating levels of leptin, resistin, adiponectin, and IL-6, contribute to cancer development by promoting inflammation and creating a tumor-promoting microenvironment rich in adipocytes. Adipocytes release leptin, a pro-inflammatory substance that stimulates cancer cell proliferation, inflammation, and invasion, altering the tumor cell metabolic pathway. Adiponectin, an insulin-sensitizing adipokine, is typically downregulated in obese individuals. It has antiproliferative, proapoptotic, and antiangiogenic properties, making it a potential cancer treatment. This narrative review offers a comprehensive examination of the molecular interconnections between obesity and cancer, drawing on an extensive, though non-systematic, survey of the recent literature. This approach allows us to integrate and synthesize findings from various studies, offering a cohesive perspective on emerging themes and potential therapeutic targets. The review explores the metabolic disturbances, cellular alterations, inflammatory responses, and shifts in the tumor microenvironment that contribute to the obesity-cancer link. Finally, it discusses potential therapeutic strategies aimed at disrupting these connections, offering valuable insights into future research directions and the development of targeted interventions.

Cancer immunotherapy has transformed cancer treatment in recent years, with immune checkpoint inhibitors (ICIs) emerging as a key therapeutic approach. ICIs work by inhibiting the mechanisms that allow tumors to evade immune detection. Although ICIs have shown promising results, especially in solid tumors, patient responses vary widely due to multiple intrinsic and extrinsic factors within the tumor microenvironment. Emerging evidence suggests that the gut microbiota plays a pivotal role in modulating immune responses at the tumor site and may even influence treatment outcomes in cancer patients receiving ICIs. This review explores the complex interactions between the gut microbiota and the tumor microenvironment, examining how these interactions could impact the effectiveness of ICI therapy. Furthermore, we discuss how dysbiosis, an imbalance in gut microbiota composition, may contribute to resistance to ICIs, and highlight microbiota-targeted strategies to potentially overcome this challenge. Additionally, we review recent studies investigating the diagnostic potential of microbiota profiles in cancer patients, considering how microbial markers might aid in early detection and stratification of patient responses to ICIs. By integrating insights from recent preclinical and clinical studies, we aim to shed light on the potential of microbiome modulation as an adjunct to cancer immunotherapy and as a diagnostic tool, paving the way for personalized therapeutic approaches that optimize patient outcomes.