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.

Probiotics exert a diverse range of immunomodulatory effects on the human gut immune system. These mechanisms encompass strengthening the intestinal mucosal barrier, inhibiting pathogen adhesion and colonization, stimulating immune modulation, and fostering the production of beneficial substances. As a result, probiotics hold significant potential in the prevention and treatment of various conditions, including inflammatory bowel disease and colorectal cancer. A pivotal mechanism by which probiotics achieve these effects is through modulating the expression of host miRNAs. miRNAs, non-coding RNA molecules, are vital regulators of fundamental biological processes like cell growth, differentiation, and apoptosis. By interacting with mRNAs, miRNAs can either promote their degradation or repress their translation, thereby regulating gene expression post-transcriptionally and modulating the immune system. This review provides a comprehensive overview of how probiotics modulate gut immune responses by altering miRNA expression levels, both upregulating and downregulating specific miRNAs. It further delves into how this modulation impacts the host's resistance to pathogens and susceptibility to diseases, offering a theoretical foundation and practical insights for the clinical utilization of probiotics in disease prevention and therapy.

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.

This study aimed to characterize salivary microbiota in patients with oral cancer using 16S rRNA amplicon sequencing. DNA was extracted from saliva samples of 23 patients with oral cancer and 95 age-matched controls. A metagenomic analysis was performed using 16S rRNA amplicon sequencing. Patients with oral cancer exhibited lower α-diversity, as indicated by the Chao-1 index, compared to the control group, and significant differences in β-diversity were observed between the two groups. At the genus level, 25 bacterial species such as Lautropia, Megasphaera, Lactobacillus, Kingella, Gemella, Staphylococcus, and Propionibacterium were identified in patients with oral cancer, with more than half being Gram-positive facultative anaerobes or anaerobes. The reduced bacterial diversity in saliva of patients with oral cancer suggests dysbiosis during oral carcinogenesis may contribute to changes in bacterial distribution within the oral cavity.

Colorectal cancer (CRC) involves uncontrolled cell growth in the colon and rectum. This study aims to explore the prevalence of key pathogenic bacteria and their role in the progression of CRC, focusing on microbial dysbiosis. This study analyzed 52 stool and tissue samples through polymerase chain reaction (PCR), real-time PCR, and bioinformatics to identify associations between pathogenic bacteria and CRC progression. PCR results revealed a significant association between the Bacteroides fragilis toxin (bft) gene and CRC progression (P = 0.001, r = 0.570). Furthermore, Real-time PCR showed significant differences in the frequency of pks+Escherichia coli in CRC stages 1 (P = 0.03), 2 (P = 0.004), and 3 (P = 0.0002) compared to the control group. Additionally, the frequency of Fusobacterium nucleatum in stage 3 CRC patients was significantly higher than in the control group (P = 0.004) and stage 1 patients (P = 0.01). Furthermore, Streptococcus gallolyticus showed similar significant differences in stage 3 patients (P = 0.004). Bioinformatics analyses using KEGG, Reactome, STRING, and dbSNP highlighted bacteria's roles in colorectal carcinogenesis, emphasizing the need for early identification and management in CRC treatment and prevention strategies. Finally, due to the limitations of the study, the use of more advanced methods and the validation of results through more reliable techniques are essential for future research.

Dysgeusia contributes to malnutrition and worsens the quality of life of patients with cancer. Despite the different strategies, there is no effective treatment for patients suffering from taste disorders provided by the pharmaceutical industry. Therefore, we developed a novel strategy for reducing side effects in cancer patients by providing a novel food supplement with the taste-modifying glycoprotein miraculin, which is approved by the European Union, as an adjuvant to medical-nutritional therapy.

A pilot randomized, parallel, triple-blind, and placebo-controlled intervention clinical trial was carried out in which 31 malnourished patients with cancer and dysgeusia receiving antineoplastic treatment were randomized into three arms-standard dose of dried miracle berries (DMBs) (150 mg DMB/tablet), high dose of DMBs (300 mg DMB/tablet), or placebo (300 mg freeze-dried strawberry)-for three months. Patients consumed a DMB or placebo tablet before each main meal (breakfast, lunch, and dinner). Using stool samples from patients with cancer, we analyzed the intestinal microbiome via nanopore methodology.

We detected differences in the relative abundances of genera Phocaeicola and Escherichia depending on the treatment. Nevertheless, only the Solibaculum genus was more abundant in the standard-dose DMB group after 3 months. At the species level, Bacteroides sp. PHL 2737 presented a relatively low abundance in both DMB groups, whereas Vescimonas coprocola presented a relatively high abundance in both treatment groups after 3 months. Furthermore, a standard dose of DMB was positively associated with TNF-α levels and Lachnoclostridium and Mediterraneibacter abundances, and a high dose of DMB was negatively associated with TNF-α levels and the relative abundance of Phocaeicola. Following the administration of a high dose of DMB, a positive correlation was observed between erythrocyte polyunsaturated fatty acids and the presence of Lachnoclostridium and Roseburia. Additionally, a positive association was identified between Phocaeicola and the acetic acid concentration of feces. There was a negative association between the relative abundance of Phocaeicola and taste perception in the high-dose DMB group.

The combination of DMB intake with nutritional treatment and individualized dietary guidance results in positive changes in the intestinal microbiome of patients with cancer and dysgeusia. Changes observed in the intestinal microbiome might contribute to maintaining an appropriate immune response in cancer patients. As the current pilot study included a limited number of participants, further clinical trials on a larger group of patients are needed to draw robust findings.

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

Cancer has long been associated with genetic and environmental factors, but recent studies reveal the important role of gut microbiota in its initiation and progression. Around 13% of cancers are linked to infectious agents, highlighting the need to identify the specific microorganisms involved. Gut microbiota can either promote or inhibit cancer growth by influencing oncogenic signaling pathways and altering immune responses. Dysbiosis can lead to cancer, while certain probiotics and their metabolites may help reestablish micro-ecological balance and improve anti-tumor immune responses. Research into targeted approaches that enhance therapy with probiotics is promising. However, the effects of probiotics in humans are complex and not yet fully understood. Additionally, methods to counteract harmful bacteria are still in development. Early clinical trials also indicate that modifying gut microbiota may help manage side effects of cancer treatments. Ongoing research is crucial to understand better how gut microbiota can be used to improve cancer prevention and treatment outcomes.

The tumor microbiome, a complex community of microbes found in tumors, has been found to be linked to cancer development, progression, and treatment outcome. However, it remains a bottleneck in distangling the relationship between the tumor microbiome and host gene expressions in tumor microenvironment, as well as their concert effects on patient survival. In this study, we aimed to decode this complex relationship by developing ASD-cancer (autoencoder-based subtypes detector for cancer), a semi-supervised deep learning framework that could extract survival-related features from tumor microbiome and transcriptome data, and identify patients' survival subtypes. By using tissue samples from The Cancer Genome Atlas database, we identified two statistically distinct survival subtypes across all 20 types of cancer Our framework provided improved risk stratification (e.g., for liver hepatocellular carcinoma, [LIHC], log-rank test, P = 8.12E-6) compared to PCA (e.g., for LIHC, log-rank test, P = 0.87), predicted survival subtypes accurately, and identified biomarkers for survival subtypes. Additionally, we identified potential interactions between microbes and host genes that may play roles in survival. For instance, in LIHC, Arcobacter, Methylocella, and Isoptericola may regulate host survival through interactions with host genes enriched in the HIF-1 signaling pathway, indicating these species as potential therapy targets. Further experiments on validation data sets have also supported these patterns. Collectively, ASD-cancer has enabled accurate survival subtyping and biomarker discovery, which could facilitate personalized treatment for broad-spectrum types of cancers.IMPORTANCEUnraveling the intricate relationship between the tumor microbiome, host gene expressions, and their collective impact on cancer outcomes is paramount for advancing personalized treatment strategies. Our study introduces ASD-cancer, a cutting-edge autoencoder-based subtype detector. ASD-cancer decodes the complexities within the tumor microenvironment, successfully identifying distinct survival subtypes across 20 cancer types. Its superior risk stratification, demonstrated by significant improvements over traditional methods like principal component analysis, holds promise for refining patient prognosis. Accurate survival subtype predictions, biomarker discovery, and insights into microbe-host gene interactions elevate ASD-cancer as a powerful tool for advancing precision medicine. These findings not only contribute to a deeper understanding of the tumor microenvironment but also open avenues for personalized interventions across diverse cancer types, underscoring the transformative potential of ASD-cancer in shaping the future of cancer care.

Compared to the general population of Hawai'i, Native Hawaiians and Other Pacific Islanders (NHPI) shoulder a disproportionately high risk for obesity-related cardiometabolic disorders, such as type 2 diabetes and cardiovascular disease. The gut microbiome is an area of rapid research interest for its role in regulating adjacent metabolic pathways, offering novel opportunities to better understand the etiology of these health disparities. Obesity and the gut microbiome are influenced by regional, racial-ethnic, and community-specific factors, limiting the generalizability of current literature for understudied populations. Additionally, anthropometric and directly measured obesity indices are variably predictive of adiposity and metabolic health risk in this diverse population. Thus, further NHPI-inclusive research is required to adequately characterize community-specific factors in the context of obesity-related disease etiology. Culturally responsible research ethics and scientific communication are crucial to conducting such research, especially among indigenous and understudied populations. In this review, we explore these limitations in current literature, emphasizing the urgent need for NHPI-inclusive research to assess community-specific factors accurately. Such accuracy in Indigenous health research may ensure that findings relevant to individual or public health recommendations and/or policies are meaningful to the communities such research aims to serve.

This review synthesizes the findings from 252 studies to explore the relationship between the oral pathogens associated with periodontitis, dental caries, and systemic diseases. Individuals with oral diseases, such as periodontitis, are between 1.7 and 7.5 times (average 3.3 times) more likely to develop systemic diseases or suffer adverse pregnancy outcomes, underscoring the critical connection between dental and overall health. Oral conditions such as periodontitis and dental caries represent a significant health burden, affecting 26-47% of Americans. The most important oral pathogens, ranked by publication frequency, include the herpes virus, C. albicans, S. mutans, P. gingivalis, F. nucleatum, A. actinomycetemcomitans, P. intermedia, T. denticola, and T. forsythia. The systemic diseases and disorders linked to oral infections, ranked similarly, include cancer, respiratory, liver, bowel, fever, kidney, complications in pregnancy, cardiovascular bacteremia, diabetes, arthritis, autoimmune, bladder, dementia, lupus, and Alzheimer's diseases. Evidence supports the efficacy of dental and periodontal treatments in eliminating oral infections and reducing the severity of systemic diseases. The substantial burden that oral pathogens have on cancer, cardiovascular diseases, Alzheimer's, diabetes, and other systemic diseases poses a significant public health crisis.

The human body hosts trillions of microorganisms throughout many diverse habitats with different physico-chemical characteristics. Among them, the oral cavity and the gut harbour some of the most dense and diverse microbial communities. Although these two sites are physiologically distinct, they are directly connected and can influence each other in several ways. For example, oral microorganisms can reach and colonize the gastrointestinal tract, particularly in the context of gut dysbiosis. However, the mechanisms of colonization and the role that the oral microbiome plays in causing or exacerbating diseases in other organs have not yet been fully elucidated. Here, we describe recent advances in our understanding of how the oral and intestinal microbiota interplay in relation to their impact on human health and disease.

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

The relevant mechanism of tumor-associated macrophages (TAMs) in the treatment of colorectal cancer patients with immune checkpoint inhibitors (ICIs) is discussed, and the application prospects of TAMs in reversing the treatment tolerance of ICIs are discussed to provide a reference for related studies. As a class of drugs widely used in clinical tumor immunotherapy, ICIs can act on regulatory molecules on cells that play an inhibitory role - immune checkpoints - and kill tumors in the form of an immune response by activating a variety of immune cells in the immune system. The sensitivity of patients with different types of colorectal cancer to ICI treatment varies greatly. The phenotype and function of TAMs in the colorectal cancer microenvironment are closely related to the efficacy of ICIs. ICIs can regulate the phenotypic function of TAMs, and TAMs can also affect the tolerance of colorectal cancer to ICI therapy. TAMs play an important role in ICI resistance, and making full use of this target as a therapeutic strategy is expected to improve the immunotherapy efficacy and prognosis of patients with colorectal cancer.

Vulvar cancer represents a small minority of annual cancer cases in America. This malignancy affects more than the physical health of the patient. This malignancy also has a negative impact on women's psychological and sexual health. This case pertains to a 49-year-old woman (G1P1001) who presented with right groin pain, fever, and chills for three days. She reported experiencing vaginal bleeding during the intercourse and had been able to palpate a mass inside her vagina for the past five years. A pelvic exam revealed a 6 cm tender mass on the left vaginal wall, which was friable and hemorrhagic on palpation, along with associated lymphadenopathy. The patient was taken to the operating room where the exophytic mass and lymphadenopathy were biopsied. Necrotic lymph nodes were removed and sent for pathology. Pathology confirmed moderately differentiated squamous cell carcinoma of the vulva. The lymph node pathology report also indicated that the necrotic nodes were infected with Fusobacterium necrophorum. Given the extent of the tumor, it was deemed largely inoperable, and the patient was recommended local radiation therapy. The patient was diagnosed with stage III vulvar cancer. This case highlights the intersection of gynecology-oncology and infectious disease, with a never-before-documented bacterial infection in the context of vulvar cancer. Fusobacterium necrophorum has been previously associated with colorectal cancers, liver abscesses, and ovarian abscesses. Further ingestion is needed to understand the role of this pathogen in the development of vulvar cancer.

A bioinformatic analysis is a promising approach to understand the relationship between the vast tumor microbiome and cancer development. In the present study, we studied the relationships between the intratumoral microbiome and classical clinical risk factors using bioinformatics analysis of the Cancer Genome Atlas (TCGA) and the Cancer Microbiome Atlas (TCMA) datasets. We used TCMA database and investigated the abundance of microbes at the genus level in solid normal tissue (n = 22) and the primary tumors of patients with head and neck squamous cell carcinoma (HNSCC) (n = 154) and identified three major tumor microbiomes, Fusobacterium, Prevotella, and Streptococcus. The tissue level of Fusobacterium was higher in primary tumors than in solid normal tissue. However, univariate and multivariate analyses of these 3 microbes showed no significant effects on patient survival. We then extracted 43, 55, or 59 genes that were differentially expressed between the over and under the median groups for Fusobacterium, Prevotella, or Streptococcus using the criteria of >2.5, >1.5, or >2.0 fold and p < 0.05 in the Mann-Whitney U test. The results of a pathway analysis revealed the association of Fusobacterium- and Streptococcus-related genes with the IL-17 signaling pathway and Staphylococcus aureus infection, while Prevotella-associated pathways were not extracted. A protein-protein interaction analysis revealed a dense network in the order of Fusobacterium, Streptococcus, and Prevotella. An investigation of the relationships between the intratumoral microbiome and classical clinical risk factors showed that high levels of Fusobacterium were associated with a good prognosis in the absence of alcohol consumption and smoking, while high levels of Streptococcus were associated with a poor prognosis in the absence of alcohol consumption. In conclusion, intratumoral Fusobacterium and Streptococcus may affect the prognosis of patients with HNSCC, and their effects on HNSCC are modulated by the impact of drinking and smoking.

The gut microbiome emerges as an integral component of precision medicine because of its signature variability among individuals and its plasticity, which enables personalized therapeutic interventions, especially when integrated with other multiomics data. This promise is further fueled by advances in next-generation sequencing and metabolomics, which allow in-depth high-precision profiling of microbiome communities, their genetic contents, and secreted chemistry. This knowledge has advanced our understanding of our microbial partners, their interaction with cellular targets, and their implication in human conditions such as inflammatory bowel disease (IBD). This explosion of microbiome data inspired the development of next-generation therapeutics for treating IBD that depend on manipulating the gut microbiome by diet modulation or using live products as therapeutics. The current landscape of artificial microbiome therapeutics is not limited to probiotics and fecal transplants but has expanded to include community consortia, engineered probiotics, and defined metabolites, bypassing several limitations that hindered rapid progress in this field such as safety and regulatory issues. More integrated research will reveal new therapeutic targets such as enzymes or receptors mediating interactions between microbiota-secreted molecules that drive or modulate diseases. With the shift toward precision medicine and the enhanced integration of host genetics and polymorphism in treatment regimes, the following key questions emerge: How can we effectively implement microbiomics to further personalize the treatment of diseases like IBD, leveraging proven and validated microbiome links? Can we modulate the microbiome to manage IBD by altering the host immune response? In this review, we discuss recent advances in understanding the mechanism underpinning the role of gut microbes in driving or preventing IBD. We highlight developed targeted approaches to reverse dysbiosis through precision editing of the microbiome. We analyze limitations and opportunities while defining the specific clinical niche for this innovative therapeutic modality for the treatment, prevention, and diagnosis of IBD and its potential implication in precision medicine.

Fecal immunochemical test (FIT) followed by colonoscopy in positive cases is commonly used for population-based colorectal cancer screening. However, specificity of FIT for colorectal cancer is not ideal and has poor performance for advanced adenoma detection. Fecal Fusobacterium nucleatum (Fn) detection has been proposed as a potential noninvasive biomarker for colorectal cancer and advanced adenoma detection. We aimed to evaluate the diagnostic performance of Fn detection using droplet digital PCR (ddPCR) in FIT samples from individuals enrolled in a colorectal cancer screening program with colorectal adenoma or cancer. We evaluated Fn presence in DNA isolated from FIT leftover material of 300 participants in a colorectal cancer screening program using ddPCR. The Fn DNA amount was classified as Fn-low/negative and Fn-high, and the association with patients' clinicopathological features and accuracy measurements was calculated. Fn-high levels were more prevalent in FIT-positive (47.2%, n = 34 of 72) than FIT-negative samples (28.9%, n = 66 of 228; P < 0.04). Among FIT-positive samples, high Fn levels were significantly more frequent in patients with cancer (CA, n = 8) when compared to normal (NT, n = 16; P = 0.02), non-advanced adenomas (NAA, n = 36; P = 0.01), and advanced adenomas (AA, n = 12; P = 0.01). Performance analysis of Fn in FIT-positive samples for colorectal cancer detection yielded an AUC of 0.8203 [confidence interval (CI), 0.6464-0.9942], with high sensitivity (100%) and specificity of 50%. Concluding, we showed the feasibility of detecting Fn in FIT leftovers using the ultrasensitive ddPCR technique. Furthermore, we highlighted the potential use of Fn levels in fecal samples to ameliorate colorectal cancer detection. Prevention Relevance: Fusobacterium nucleatum detection by droplet digital PCR could prioritize the selection of fecal immunochemical test-positive individuals who might benefit the most from the colonoscopy procedure.

The human body is colonized by trillions of microorganisms in a symbiotic relationship. The oral cavity represents one of the most abundant microbial habitats in our body. Advances in sequencing techniques provide a more detailed understanding of the oral microbiota and how imbalances between bacteria, the phenomenon of dysbiosis, can affect not only the development of dental caries or inflammation within the oral cavity but also systemic diseases and cancers in distant locations. This narrative review evaluates the relationship between oral microbiota and its impact on gastrointestinal cancers. Using the keywords "oral microbiota 'AND' gastrointestinal cancers", the PubMed Web of Science and Scopus databases were searched for articles published between 2014 and 2024. Based on the review, the relationship between oral microbiota and oral, esophageal, gastric, colorectal, hepatocellular, and pancreatic cancers was described. Potential oncogenic mechanisms exploited by the microbiota such as the production of pro-inflammatory cytokines, induction of abnormal immune responses, and disruption of cell metabolic pathways were assessed. Further research and a thorough understanding of the impact of the oral microbiota on the development of cancers of the gastrointestinal tract may play a key role in their prevention, diagnosis, and treatment in the future.

The impact of oral flora on intestinal micro-environment and related diseases has been widely reported, but its role in colorectal cancer (CRC) remains elusive.

A Two-sample Mendelian Randomization (TSMR) analysis was conducted to explore the causal relationship between oral flora and CRC, with the Inverse-Variance Weighted (IVW) serving as the primary method for evaluating this causal relationship. Data on the oral flora were derived from human samples from the tongue and saliva, with all cohort populations originating from Asia. In addition, 2 independent external cohorts were used to validate the positive results and perform a meta-analysis of the final results. Lastly, to balance the effect of positive oral flora on CRC, a Multivariate Mendelian Randomization (MVMR) analysis was also performed.

The TSMR analysis revealed that 17 oral flora may have a causal relationship with CRC in the training cohort. Among them, s Haemophilus, g Fusobacterium, s Metamycoplasma salivarium, and s Mogibacterium pumilum were validated in two testing cohorts. Intriguingly, after integrating the results of the 3 cohorts for meta-analysis, 16 associations remained significant. In the training cohort, MVMR analysis demonstrated that s Capnocytophaga ochracea and s Metamycoplasma salivarium retained statistical significance. In one of the testing cohorts, s Metamycoplasma salivarium, s Streptococcus anginosus, and s Streptococcus sanguinis retained statistical significance. In the other testing cohort, s Metamycoplasma salivarium, s Haemophilus, and g Fusobacterium remained significant.

s Haemophilus, g Fusobacterium, s Metamycoplasma salivarium, and s Mogibacterium pumilum have a solid causal relationship with the occurrence and development of CRC.

Obesity and colorectal cancer are global public health issues, with the prevalence of both conditions increasing over the last 4 decades. In the United States alone, the prevalence of obesity is greater than 40%, and this percentage is projected to increase past 50% by 2030. This review focuses on understanding the association between obesity and the risk of colorectal cancer while also highlighting hypotheses about molecular mechanisms underlying the link between these disease processes. We also consider whether those linkages can be disrupted via weight loss therapies, including lifestyle modifications, pharmacotherapy, bariatric surgery, and endobariatrics.

Neoadjuvant immune checkpoint blockade (ICB) has achieved significant success in treating various cancers, leading to improved therapeutic responses and survival rates among patients. However, in colorectal cancer (CRC), ICB has yielded poor results in tumors that are mismatch repair proficient, microsatellite-stable, or have low levels of microsatellite instability (MSI-L), which account for up to 95% of CRC cases. The underlying mechanisms behind the lack of immune response in MSI-negative CRC to immune checkpoint inhibitors remain an open conundrum. Consequently, there is an urgent need to explore the intrinsic mechanisms and related biomarkers to enhance the intratumoral immune response and render the tumor "immune-reactive". Intestinal microbes, such as the oral microbiome member Fusobacterium nucleatum (F. nucleatum), have recently been thought to play a crucial role in regulating effective immunotherapeutic responses. Herein, we advocate the idea that a complex interplay involving F. nucleatum, the local immune system, and the tumor microenvironment (TME) significantly influences ICB responses. Several mechanisms have been proposed, including the regulation of immune cell proliferation, inhibition of T lymphocyte, natural killer (NK) cell function, and invariant natural killer T (iNKT) cell function, as well as modification of the TME. This review aims to summarize the latest potential roles and mechanisms of F. nucleatum in antitumor immunotherapies for CRC. Additionally, it discusses the clinical application value of F. nucleatum as a biomarker for CRC and explores novel strategies, such as nano-delivery systems, for modulating F. nucleatum to enhance the efficacy of ICB therapy.

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?

Gut microbiota is closely related to the occurrence and development of colorectal cancer (CRC). However, the differences in bacterial co-abundance groups (CAGs) between tumor tissue (TT) and normal tissue (NT), as well as their associations with clinical features, are needed to be clarified.

Bacterial 16 S rRNA sequencing was performed by using TT samples and NT samples of 251 patients with colorectal cancer. Microbial diversity, taxonomic characteristics, microbial composition, and functional pathways were compared between TT and NT. Hierarchical clustering was used to construct CAGs.

Four CAGs were grouped in the hierarchical cluster analysis. CAG 2, which was mainly comprised of pathogenic bacteria, was significantly enriched in TT samples (2.27% in TT vs. 0.78% in NT, p < 0.0001). CAG 4, which was mainly comprised of non-pathogenic bacteria, was significantly enriched in NT samples (0.62% in TT vs. 0.79% in NT, p = 0.0004). In addition, CAG 2 was also significantly associated with tumor microsatellite instability (13.2% in unstable vs. 2.0% in stable, p = 0.016), and CAG 4 was positively correlated with the level of CA199 (r = 0.17, p = 0.009).

Our research will deepen our understanding of the interactions among multiple bacteria and offer insights into the potential mechanism of NT to TT transition.

The intestinal architecture of piglets is vulnerable to disruption during weaning transition and leads to diarrhea, frequently accompanied by inflammation and metabolic disturbances (including amino acid metabolism). Tryptophan (Trp) plays an essential role in orchestrating intestinal immune tolerance through its metabolism via the kynurenine, 5-hydroxytryptamine, or indole pathways, which could be dictated by the gut microbiota either directly or indirectly. Emerging evidence suggests a strong association between piglet diarrhea and Trp metabolism. Here we aim to summarize the intricate balance of microbiota-host crosstalk by analyzing alterations in both the host and microbial pathways of Trp and discuss how Trp metabolism may affect piglet diarrhea. Overall, this review could provide valuable insights to explore effective strategies for managing piglet diarrhea and the related challenges.

Liver metastasis is a major cause of mortality in patients with advanced stages of colorectal cancer (CRC). The gut microbiota has been demonstrated to influence the progression of liver diseases, potentially providing novel perspectives for diagnosis, treatment and research. However, the gut microbial characteristics in CRC with liver metastasis (LM) and with no liver metastasis (NLM) have not yet been fully established. In the present study, high-throughput 16S RNA sequencing technology was employed, in order to examine the gut microbial richness and composition in patients with CRC with LM or NLM. A discovery cohort (cohort 2; LM=18; NLM=36) and a validation cohort (cohort 3; LM=13; NLM=41) were established using fresh feces. In addition, primary carcinoma tissue samples were also analyzed (LM=8 and NLM=10) as a supplementary discovery cohort (cohort 1). The findings of the present study indicated that the intestinal microbiota richness and diversity were increased in the LM group as compared to the NLM group. A significant difference was observed in species composition between the LM and NLM group. In the two discovery cohorts with two different samples, the dominant phyla were consistent, but varied at lower taxonomic levels. Phylum Fusobacteria presented consistent and significant enrichment in LM group in both discovery cohorts. Furthermore, with the application of a random forest model and receiver operator characteristic curve analysis, Fusobacteria was identified as a potential biomarker for LM. Moreover, Fusobacteria was also a poor prognosis factor for survival. Importantly, the findings were reconfirmed in the validation cohort. On the whole, the findings of the present study demonstrated that CRC with LM and NLM exhibit distinct gut microbiota characteristics. Fusobacteria detection thus has potential for use in predicting LM and a poor prognosis of patients with CRC.

Tumor-resident microbes (TRM) are an integral component of the tumor microenvironment (TME). TRM can influence tumor growth, distant dissemination, and response to therapies by interfering with molecular pathways in tumor cells as well as with other components of the TME. Novel technologies are improving the identification and visualization of cell type-specific microbes in the TME. The mechanisms that mediate the role of TRM at the primary tumors and metastatic sites are being elucidated. This knowledge is providing novel perspectives for targeting microbes or using microbial interventions for cancer interception or therapy.

Renal cell carcinoma (RCC) accounts for about 2% of cancer diagnoses and deaths worldwide. Recent studies emphasized the critical involvement of microbial populations in RCC from oncogenesis, tumor growth, and response to anticancer therapy. Microorganisms have been shown to be involved in various renal physiological and pathological processes by influencing the immune system function, metabolism of the host and pharmaceutical reactions. These findings have extended our understanding and provided more possibilities for the diagnostic or therapeutic development of microbiota, which could function as screening, prognostic, and predictive biomarkers, or be manipulated to prevent RCC progression, boost anticancer drug efficacy and lessen the side effects of therapy. This review aims to present an overview of the roles of microbiota in RCC, including pertinent mechanisms in microbiota-related carcinogenesis, the potential use of the microbiota as RCC biomarkers, and the possibility of modifying the microbiota for RCC prevention or treatment. According to these scientific findings, the clinical translation of microbiota is expected to improve the diagnosis and treatment of RCC.

Evidence supports significant interactions among microbes, immune cells, and tumor cells in at least 10%-20% of human cancers, emphasizing the importance of further investigating these complex relationships. However, the implications and significance of tumor-related microbes remain largely unknown. Studies have demonstrated the critical roles of host microbes in cancer prevention and treatment responses. Understanding interactions between host microbes and cancer can drive cancer diagnosis and microbial therapeutics (bugs as drugs). Computational identification of cancer-specific microbes and their associations is still challenging due to the high dimensionality and high sparsity of intratumoral microbiome data, which requires large datasets containing sufficient event observations to identify relationships, and the interactions within microbial communities, the heterogeneity in microbial composition, and other confounding effects that can lead to spurious associations. To solve these issues, we present a bioinformatics tool, microbial graph attention (MEGA), to identify the microbes most strongly associated with 12 cancer types. We demonstrate its utility on a dataset from a consortium of nine cancer centers in the Oncology Research Information Exchange Network. This package has three unique features: species-sample relations are represented in a heterogeneous graph and learned by a graph attention network; it incorporates metabolic and phylogenetic information to reflect intricate relationships within microbial communities; and it provides multiple functionalities for association interpretations and visualizations. We analyzed 2,704 tumor RNA sequencing samples and MEGA interpreted the tissue-resident microbial signatures of each of 12 cancer types. MEGA can effectively identify cancer-associated microbial signatures and refine their interactions with tumors.

Studying the tumor microbiome in high-throughput sequencing data is challenging because of the extremely sparse data matrices, heterogeneity, and high likelihood of contamination. We present a new deep learning tool, MEGA, to refine the organisms that interact with tumors.

The gastrointestinal (GI) tract of multicellular organisms, especially mammals, harbors a symbiotic commensal microbiota with diverse microorganisms including bacteria, fungi, viruses, and other microbial and eukaryotic species. This microbiota exerts an important role on intestinal function and contributes to host health. The microbiota, while benefiting from a nourishing environment, is involved in the development, metabolism and immunity of the host, contributing to the maintenance of homeostasis in the GI tract. The immune system orchestrates the maintenance of key features of host-microbe symbiosis via a unique immunological network that populates the intestinal wall with different immune cell populations. Intestinal epithelium contains lymphocytes in the intraepithelial (IEL) space between the tight junctions and the basal membrane of the gut epithelium. IELs are mostly CD8+ T cells, with the great majority of them expressing the CD8αα homodimer, and the γδ T cell receptor (TCR) instead of the αβ TCR expressed on conventional T cells. γδ T cells play a significant role in immune surveillance and tissue maintenance. This review provides an overview of how the microbiota regulates γδ T cells and the influence of microbiota-derived metabolites on γδ T cell responses, highlighting their impact on immune homeostasis. It also discusses intestinal neuro-immune regulation and how γδ T cells possess the ability to interact with both the microbiota and brain.

The gut microbiota's influence on human tumorigenesis is a burning topic in medical research. With the new ontological perspective, which considers the human body and its pathophysiological processes as the result of the interaction between its own eukaryotic cells and prokaryotic microorganisms living in different body niches, great interest has arisen in the role of the gut microbiota on carcinogenesis. Indeed, dysbiosis is currently recognized as a cancer-promoting condition, and multiple molecular mechanisms have been described by which the gut microbiota may drive tumor development, especially colorectal cancer (CRC). Metastatic power is undoubtedly one of the most fearsome features of neoplastic tissues. Therefore, understanding the underlying mechanisms is of utmost importance to improve patients' prognosis. The liver is the most frequent target of CRC metastasis, and new evidence reveals that the gut microbiota may yield an effect on CRC diffusion to the liver, thus defining an intriguing new facet of the so-called "gut-liver axis". In this review, we aim to summarize the most recent data about the microbiota's role in promoting or preventing hepatic metastasis from CRC, highlighting some potential future therapeutic targets.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide, and its incidence continues to rise, particularly in developing countries. The advent of immune checkpoint inhibitors (ICIs) has represented a significant advancement in CRC treatment. Deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H) serves as a biomarker for immunotherapy, with dMMR/MSI-H CRC exhibiting significantly better response rates to immunotherapy compared to proficient mismatch repair (pMMR)or microsatellite stable (MSS) CRC. While some progress has been made in the treatment of pMMR/MSS CRC in recent years, it remains a challenging issue in clinical practice. The tumor microenvironment (TME) plays a crucial role not only in the development and progression of CRC but also in determining the response to immunotherapy. Understanding the characteristics of the TME in pMMR/MSS CRC could offer new insights to enhance the efficacy of immunotherapy. In this review, we provide an overview of the current research progress on the TME characteristics and advancements in immunotherapy for pMMR/MSS CRC.

Fusobacterium nucleatum is one of the predominant oral bacteria in humans. However, this bacterium is enriched in colorectal cancer (CRC) tissues and may be involved in CRC development. Our previous research suggested that F. nucleatum is present in CRC tissues originating from the oral cavity using a traditional strain-typing method [arbitrarily primed polymerase chain reaction (AP-PCR)]. First, using whole-genome sequencing, this study confirmed an exemplary similarity between the oral and tumoral strains derived from each patient with CRC. Second, we successfully developed a method to genotype this bacterium at the strain level, targeting the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated system, which is hypervariable (defined as F. nucleatum-strain genotyping PCR). This method can identify F. nucleatum strains in cryopreserved samples and is significantly superior to traditional AP-PCR, which can only be performed on isolates. The new methods have great potential for application in etiological studies of F. nucleatum in CRC.

Colorectal cancer (CRC) is a malignancy that manifests in serial stages and has been observed to have an escalating incidence in modern societies, causing a significant global health problem. The development of CRC is influenced by various exogenous factors, including lifestyle, diet, nutrition, environment, and microbiota, that can affect host cells, including immune cells. Various immune dysfunctions have been recognized in patients with CRC at different stages of this disease. The signature of microbiota in the development of CRC-inflammation related to obesity, diet, and reactive host cells, such as dendritic cells (DCs)-has been highlighted by many studies. This study focuses on DCs, the primary cellular mediators linking innate and adaptive immune responses against cancer. In addition, this review focuses on the role of microbiota in dysbiosis and how it affects DCs and, in turn, the immune response and progression of CRC by stimulating different sets of T cells. Additionally, DCs' role in protecting this delicate balance is examined. This is to determine how gene yields of commensal microbiota may be critical in restoring this balance when disrupted. The stages of the disease and major checkpoints are discussed, as well as the role of the C-type lectin receptor of immature DCs pattern recognition receptor in CRC. Finally, based on a thorough examination of worldwide clinical studies and recent advancements in cancer immunotherapy, it is recommended that innovative approaches that integrate DC vaccination strategies with checkpoint inhibitors be considered. This approach holds great promise for improving CRC management.

The human microbiota is widely recognized as providing crucial health benefits to its host, specifically by modulating immune homeostasis. Microbial imbalance, known as dysbiosis, is linked to several conditions in the body. The oral cavity and gut host the two largest microbial communities playing a major role in microbial-associated diseases. While the oral-gut axis has been previously explored, our review uniquely highlights the significance of incorporating the circulatory system into this axis. The interaction between immune cells, inflammatory factors, circulating bacteria, and microbial metabolites influences the homeostasis of both the oral and gut microbiota in a bidirectional manner. In this comprehensive review, we aim to describe the bacterial components of the oral-gut-circulatory axis in both health and disease, with a specific focus on colon cancer.

A growing number of studies have shown that gut microbiota (GM) plays an essential role in the occurrence and development of colorectal cancer (CRC). The current body of research exploring the relationship between CRC and GM is vast. Nevertheless, bibliometric studies in this area have not yet been reported. This study aimed to explore the hotspots and frontiers of research on GM and CRC in the past 20 years, which may provide a reference for researchers in this field. The Web of Science Core Collection database was searched for publications on CRC and GM from 2002 to 2022. The scientometric softwares CiteSpace and VOSviewer were used to visually analyze the countries, institutions, authors, journals, and keywords involved in the literature. Keywords co-occurrence, cluster, and burst analysis were utilized to further explore the current state and development trends of research on GM and CRC. A total of 2158 publications were included in this study, with a noticeably rising annual publication trend. The majority of these papers are from 80 nations, primarily China and the USA. J Yu was the most active author and WS Garrett has the highest citation. Among all institutions, Shanghai Jiao Tong University has the largest number of papers. Most of the publications were published in the International Journal of Molecular Sciences, with Science being the most frequently cited journal. The 4 main clusters mainly involved probiotics, inflammation, molecular mechanisms, and research methods. Current research hotspots included "Fusobacterium nucleatum," "Escherichia coli," etc. Newly emerging research has focused predominantly on immune response, gene expression, and recent strategies for the treatment of CRC with GM. The relationship between GM and CRC will continue to be a hot research area. Changes in the composition of GM in patients with CRC, the potential molecular mechanisms as well as probiotics and natural products used in the treatment of CRC have been the focus of current research and hotspots for future studies.

The gut microbiome is mainly composed of microbiota and mycobiota, both of which play important roles in the development of the host immune system, metabolic regulation, and maintenance of intestinal homeostasis. With the increasing awareness of the pathogenic essence of infectious, immunodeficiency, and tumor-related diseases, the interactions between gut bacteria, fungi, and host immunity have been shown to directly influence the disease process or final therapeutic outcome, and collaborative and antagonistic relationships are commonly found between bacteria and fungi. Interventions represented by probiotics, prebiotics, engineered probiotics, fecal microbiota transplantation (FMT), and drugs can effectively modulate the triple interactions. In particular, traditional probiotics represented by Bifidobacterium and Lactobacillus and next-generation probiotics represented by Akkermansia muciniphila and Faecalibacterium prausnitzii showed a high enrichment trend in the gut of patients with a high response to inflammation remission and tumor immunotherapy, which predicts the potential medicinal value of these beneficial microbial formulations. However, there are bottlenecks in all these interventions that need to be broken. Meanwhile, further unraveling the underlying mechanisms of the "triple interactions" model can guide precise interventions and ultimately improve the efficiency of interventions on the host gut microbiome and immune modulation, thus directly or indirectly improving anti-inflammatory and tumor immunotherapy effects.

Colorectal cancer (CRC) ranks third in terms of incidence among all kinds of cancer. The main cause of death is metastasis. Recent studies have shown that the gut microbiota could facilitate cancer metastasis by promoting cancer cells proliferation, invasion, dissemination, and survival. Multiple mechanisms have been implicated, such as RNA-mediated targeting effects, activation of tumor signaling cascades, secretion of microbiota-derived functional substances, regulation of mRNA methylation, facilitated immune evasion, increased intravasation of cancer cells, and remodeling of tumor microenvironment (TME). The understanding of CRC metastasis was further deepened by the mechanisms mentioned above. In this review, the mechanisms by which the gut microbiota participates in the process of CRC metastasis were reviewed as followed based on recent studies.