The global prevalence of metabolic diseases is on the increase, and it has become a significant threat to the health and lives of individuals. Ergothioneine (EGT) is a natural betaine amino acid found in various foods, particularly mushrooms. EGT cannot be synthesized by mammals; it is absorbed into small intestinal epithelial cells by a cationic protein, the novel organic cation transporter 1 (OCTN1), and transported to certain organs including liver, spleen, kidney, lung, heart, eyes and brain. EGT has been reported to exhibit antioxidant, anti-inflammatory, anti-apoptotic, anti-aging, and metal-chelating effects. The unique chemical properties and biological functions of EGT position it as a promising candidate for the research and treatment of metabolic diseases. This review summarizes EGT's capacities, potential therapeutic effects on multiple metabolic diseases, and their specific mechanisms. Finally, we outline challenges for future research on EGT and aspire to establish it as a prospective therapeutic agent for metabolic diseases.

The evidence suggests that the microbiome plays a crucial role in cancer development. The oral cavity has many microorganisms that can influence oral cancer progression. Understanding the mechanisms and signaling pathways of the oral, gum, and teeth microbiome in tumor progression can lead to new treatment strategies. Probiotics, which are friendly microorganisms, have shown potential as anti-cancer agents. These positive characteristics of probiotic strains make them suitable for cancer prevention or treatment. The oral-gut microbiome axis supports health and homeostasis, and imbalances in the oral microbiome can disrupt immune signaling pathways, epithelial barriers, cell cycles, apoptosis, genomic stability, angiogenesis, and metabolic processes. Changes in the oral microbiome in oral cancer may suggest using probiotics-based treatments for their direct or indirect positive roles in cancer development, progression, and metastasis, specifically oral squamous cell carcinoma (OSCC). Here, reported relationships between probiotics, oral microbiota, and oral cancer are summarized.

Objectives: The dietary inflammatory index (DII), a validated tool for assessing the inflammatory potential of diet, has been widely identified as a significant risk factor for colorectal cancer (CRC). However, its role as a prognostic factor for CRC remains unexplored. This study examined the impact of preoperative dietary inflammation on clinical and oncologic outcomes following CRC surgery. Methods: The study population consisted of 126 patients who had surgical procedures for CRC and completed a food frequency questionnaire (FFQ) preoperatively between January 2018 and June 2020. Results: An optimal DII cut-off value of 0.90182 was used to categorize patients into the high-DII (n = 28) and low-DII (n = 98) groups. The high-DII group exhibited an older age (71.5 vs. 67.0, p = 0.020) and a significantly higher complication risk within 30 days postoperatively than the low-DII group (57.1% vs. 35.7%, p = 0.042). Other perioperative clinical outcomes did not demonstrate any significant differences between the two groups. The 5-year overall survival (OS) rates were 90.4% and 41.3% in the low-DII and high-DII groups, respectively, in univariate survival analysis (p = 0.044). However, no statistical difference was observed in the disease-free survival (DFS) rate. In the multivariate survival analysis, low-DII (hazard ratio [HR]: 0.118; 95% confidence interval [CI]: 0.023-0.613, p = 0.011) and M1 stage (HR: 10.910; 95% CI: 1.491-79.847, p = 0.019) were identified as independent prognostic factors for OS, while perineural invasion (HR: 3.495; 95% CI: 1.059-11.533, p = 0.040) served as an independent prognostic factor for DFS. Conclusions: A high preoperative DII score, indicative of an inflammatory dietary pattern, was correlated with increased postoperative complications and functioned as an independent prognostic indicator for OS.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted, repetitive behaviors or interests. Studies have revealed that gut microbiota and their metabolism play important roles in ASD, and become the underlying mechanisms of ASD.

In this study, we performed long-read 16S rRNA sequencing and untargeted metabolomics to comprehensively characterize the profiles of gut microbiota and fecal metabolites in 34 ASD patients and 18 healthy controls. The associations between gut microbiota, fecal metabolites and clinical symptoms were analyzed to screen related biomarkers for ASD.

The results showed the similarity of the overall microbial richness and diversity between ASD patients and controls, however, some specific bacterial taxa exhibited significant differences, including Klebsiella and Escherichia-Shigella at genera level, and Clostridium-sporogenes, Escherichia-coli-O157H7 and Bacteroides-ovatus at species level. The fecal metabolomics validated that a lot of metabolites had significantly differential levels, including a series of organic acids, amino acids and dopamine.

The associations of gut microbiota and fecal metabolites might shed new light on the pathogenesis of ASD and help us to understand the importance of gut microbiota as potential biomarkers and therapeutic targets in the development of ASD.

Colorectal adenomas (CRA) are the primary precancerous lesions leading to colorectal cancer (CRC). Early detection and intervention of CRA can significantly reduce the incidence of CRC. We investigated the relationships between the gut microbiome and the expression levels of PD-L1, IL-6, and IFN-γ at different CRA stages.

Participants were divided into normal, non-advanced adenoma (NAA), and advanced adenoma (AA) groups. PD-L1 expression in collected tissues was analyzed via immunohistochemistry (IHC) and Western blotting. Serum IL-6 and IFN-γ levels were measured using Enzyme-Linked Immunosorbent Assay (ELISA). 16S rRNA gene sequencing was used to examine gut microbiota changes, with correlation analysis to assess microbial influences on CRA progression.

The main differences in bacterial composition among the three groups were found within the Firmicutes and Bacteroidetes phyla. In the normal vs. NAA comparison, Clostridium sensu stricto, Faecalimonas, Gemmiger, and Ruminococcus were more abundant in the normal group, while Solobacterium was enriched in the NAA group. For the normal vs. AA comparison, the normal group was enriched with Anaerostipes, Blautia, Clostridium sensu stricto, Intestinibacter, Phocaeicola, and Turicibacter, whereas Solobacterium was more abundant in the AA group. In the NAA vs. AA comparison, the NAA group exhibited higher levels of Blautia, Faecalimonas, and Turicibacter relative to the AA group. Anaerostipes and Blautia are positively correlated with taurine and hypotaurine metabolism, propanoate metabolism, and zeatin biosynthesis. PD-L1 protein levels progressively increase with CRA advancement. Additionally, Faecalimonas, and Solobacterium were negatively associated with IFN-γ, while Gemmiger, and Anaerostipes were positively associated with IL-6.

This study highlights the dynamic alterations in gut microbiota composition and their potential influence on the regulation of inflammatory cytokines and PD-L1 expression during CRA progression. The enrichment of protective taxa, such as Anaerostipes and Blautia, in the normal group emphasizes their potential role in mitigating adenoma progression. Dietary modulation to promote the proliferation of these beneficial bacteria could serve as a promising strategy to improve colorectal health. Future research should further explore the specific relationships between dietary components, gut microbiota, and metabolic pathways, and assess the effects of dietary interventions on gut health.

Colorectal cancer (CRC) ranks as the third most common cancer worldwide, with its incidence steadily increasing due to an aging demographic and various lifestyle-related risk factors, including poor nutrition, tobacco use, sedentary behaviour and obesity. These factors promote the risk of colorectal cancer by inducing chronic colonic inflammation, a principal catalyst of carcinogenesis. This review delves into evidence that suggests that metabolic abnormalities mediated through inflammatory responses are fundamental in the progression of CRC. This dysregulation of essential metabolic pathways in colorectal cancer, facilitates tumor proliferation, immune evasion, and metastasis. Additionally, this review explores how inflammatory mediators, and dietary carcinogens induce metabolic alterations, fostering a pro-tumorigenic milieu. Special focus is placed on the aryl hydrocarbon receptor (AhR) as a pivotal metabolic regulator that links inflammation and tumor metabolism, elucidating its function in the reconfiguration of cellular energetics and the inflammatory microenvironment. Furthermore, this review also focuses on clarifying the relationship between inflammation, metabolic dysregulation, and the progression of CRC, so as to identify potential therapeutic targets.

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. The current investigation aimed to assess the chemoprotective effects of pterostilbene against 1,2-dimethylhydrazine (DMH)-induced colorectal cancer in mice. An in-silico study was conducted to perform docking studies against nuclear factor kappa factor (NF-κB). CRC was induced in mice by administering DMH (20 mg/kg) subcutaneously, and the mice were subsequently administered various dosages of pterostilbene (5, 10, and 15 mg/kg). At the end of the study, various biochemical parameters, including inflammatory cytokines, inflammatory markers, and antioxidant enzymes, were examined. Additionally, the mice's stools were collected for the analysis of intestinal microbiota. A total of 5 hydrogen bonds were identified between NF-κB and pterostilbene using LigPlot+. Pterostilbene significantly (p < 0.001) reduced tumor incidence, tumor weight, and increased body weight. Pterostilbene significantly (p < 0.001) altered the levels of lipid peroxidation, reduced glutathione, superoxide dismutase, glutathione peroxidase, and catalase as well as the activity of both phase I and phase II enzymes. Furthermore, pterostilbene significantly (p < 0.001) decreased the levels of proinflammatory cytokines such as tumor necrosis factor-α, interleukin-6, interferon-γ, and interleukin-1β, while increasing the levels of anti-inflammatory cytokines like interleukin-4 and interleukin-10. Pterostilbene considerably suppressed the levels of cyclooxygenase-2 and prostaglandin E2, as well as inducible nitric oxide synthase and simultaneously elevated the levels of apoptosis-related parameters, including caspase-3, caspase-8, and caspase-9. Moreover, pterostilbene significantly reduced the abundance of Staphylococcus in the intestinal microbiota and enhanced the levels of beneficial bacteria, such as Bifidobacterium, Akkermansia, and Lactobacillus. Pterostilbene demonstrated a chemoprotective effect against CRC by effectively reducing oxidative stress, mitigating inflammatory responses, and inducing alterations in gut microbiota levels.

Colorectal cancer (CRC) represents a significant global health challenge, with approximately 1.8 million new cases diagnosed annually and a mortality toll exceeding 881,000 lives each year. This study aimed to evaluate the chemoprotective efficacy of Cyanidin-3-glucoside (C3G) in a rat model of CRC induced by 1,2-dimethylhydrazine (DMH). Rats were stratified into groups and administered C3G at doses of 10 and 15 mg/kg following DMH exposure to initiate CRC. Key parameters, including organ weights, tumor burdens, and biochemical markers, were meticulously assessed. Administration of C3G significantly restored body weight while reducing the weights of colon and spleen tissues. Moreover, C3G treatment substantially suppressed tumor incidence and weight in DMH-induced CRC rats. Biochemical analysis revealed that C3G markedly reduced levels of CFA, CA19.9, LDH, and nitric oxide (NO). It also modulated lipid profiles, antioxidant activities, and the expression of both Phase I and II enzymes. Inflammatory mediators, including TNF-α, IL-1β, IL-1α, IL-2, IL-4, IL-6, IL-10, IL-12, and IL-17, were significantly downregulated. Notably, C3G inhibited inflammatory markers such as COX-2, PGE2, iNOS, and NF-κB while promoting Caspase-3, -6, and -9 activity. Furthermore, it regulated the Bax/Bcl-2 apoptotic axis, reducing the Bcl-2/Bax ratio. Cyanidin-3-glucoside demonstrated potent chemopreventive effects against colorectal cancer in this experimental model. Its mechanism of action is likely mediated through modulation of NF-κB and the Bcl-2/Bax/Caspase pathway, suggesting its potential as a therapeutic agent in CRC management.

Emerging evidence indicates a correlation between inflammation and the development and progression of cancer. Among the various inflammatory signals, interleukin-17 (IL-17) family cytokines serve as a critical link between inflammation and cancer. IL-17 is a highly versatile pro-inflammatory cytokine that plays a pivotal role in host defense, tissue repair, the pathogenesis of inflammatory diseases, and cancer progression. During the early stages of tumorigenesis, IL-17 signaling directly promotes the proliferation of tumor cells. Conversely, IL-17 has been shown to exhibit antitumor immunity in several models of grafted subcutaneous tumors. Additionally, dynamic changes in the microbiome can influence the secretion of IL-17, thereby affecting tumor development. The specific role of IL-17 is contingent upon its functional classification, spatiotemporal characteristics, and the stage of tumor development. In this review, we introduce the fundamental biology of IL-17 and the expression profile of its receptors in cancer, while also reviewing and discussing recent advancements regarding the pleiotropic effects and mechanisms of IL-17 in inflammation-related cancers. Furthermore, we supplement our discussion with insights into the mechanisms by which IL-17 impacts cancer progression through interactions with the microbiota, and we explore the implications of IL-17 in cancer therapy. This comprehensive analysis aims to enhance our understanding of IL-17 and its potential role in cancer treatment.

Following neoplasms of the lung and breast, colorectal cancer (CRC) is the third most frequent malignancy globally. Screening for CRC at the age of 50 years is strongly encouraged for prompt earlier diagnosis owing to prognoses being greatly correlated with time of detection and cancer staging.

This review aimed to elucidate the most recent advancements in the detection of CRC, with an emphasis on the latest innovations in diagnostic molecular biomarkers in conjunction with radiological imaging alongside stool-based tests for CRC screening.

A comprehensive review of the literature was performed, focusing on specific terms in different electronic databases, including that of PubMed/MEDLINE. Keywords pertaining to "colorectal cancer," "diagnosis," "screening," "imaging," and "biomarkers," among others, were employed in the search strategy. Articles screened and evaluated were deemed relevant to the study aim and were presented in the medium of the English language.

There have been several innovations in the diagnostics and identification of CRC. These generally comprise molecular biomarkers, currently being studied for suitability in disease detection. Examples of these include genetic, epigenetic, and protein biomarkers. Concurrently, recent developments in CRC diagnostics highlight the advancements made in radiological imaging that offer precise insights on tumor biology in addition to morphological information. Combining these with statistical methodologies will increase the sensitivity and specificity of CRC diagnostics. However, putting these strategies into reality is hampered by several issues.

Progress in diagnostic technology alongside the identification of a few prognostic predictive molecular biomarkers suggested great promise for prompt detection and management of CRC. This clearly necessitates further efforts to learn more in this specific sector.

Background/Objectives: Chronic inflammation and psychosocial factors significantly influence cancer progression and patient behavior in seeking medical care. Understanding their interplay is essential for enhancing early detection and developing personalized treatment strategies. This study aims to develop a comprehensive patient profiling model by comparing non-melanoma skin cancer (NMSC) and colorectal cancer (CRC). The goal is to identify common and distinct patterns in inflammation and psychosocial factors that affect disease progression and clinical presentation. Methods: We conducted a comparative analysis of patients diagnosed with NMSC and CRC, integrating clinical data with sociodemographic and psychological assessments. Advanced neural network algorithms were employed to detect subtle patterns and interactions among these factors. Based on the analysis, a cancer risk assessment questionnaire was developed to stratify patients into low-, moderate-, and high-risk categories. Results: Patients with low systemic inflammation and adequate vagal tone, supported by a stable family environment, demonstrated heightened sensitivity to subclinical symptoms, enabling earlier diagnosis and timely intervention. Conversely, patients with high systemic inflammation and reduced vagal tone, often influenced by chronic stress and unstable family environments, presented at more advanced disease stages. The developed risk assessment tool effectively classified patients into distinct risk categories, facilitating targeted preventive measures and personalized therapeutic strategies. Neural network profiling revealed significant interactions between biological and psychosocial factors, enhancing our understanding of their combined impact on cancer progression. Conclusions: The integrated profiling approach and the newly developed risk assessment questionnaire have the potential to transform cancer management by improving early detection, personalizing treatment strategies, and addressing psychosocial factors. This model not only enhances clinical outcomes and patient quality of life but also offers a framework adaptable to other cancer types, promoting a holistic and patient-centered approach in oncology.

Many systemic diseases, including Alzheimer disease (AD), diabetes mellitus (DM) and cardiovascular disease, are associated with microbiota dysbiosis. The oral and intestinal microbiota are directly connected anatomically, and communicate with each other through the oral-gut microbiome axis to establish and maintain host microbial homeostasis. In addition to directly, periodontal bacteria may also be indirectly involved in the regulation of systemic health and disease through the disturbed gut. This paper provides evidence for the role of periodontal bacteria in systemic diseases via the oral-gut axis and the far-reaching implications of maintaining periodontal health in reducing the risk of many intestinal and parenteral diseases. This may provide insight into the underlying pathogenesis of many systemic diseases and the search for new preventive and therapeutic strategies.

Recently, cyclomodulins have been identified in Escherichia coli (E. coli), which can induce dysplastic damage. This work aimed to determine the dysplastic activity of cyclomodulin-harboring E. coli isolated from CRC patients, obese and normal-weight subjects in a mouse model. Forty-two mice were pretreated with streptomycin, azoxymethane, and dextran sodium sulfate. Mice were infected with E. coli pks + isolated from a CRC patient, with E. coli pks + cif + isolated from obese or normal-weight subjects, or with E. coli HB101. The presence of cyclomodulin-harboring E. coli in the feces, weight loss, changes in fecal consistency, and the presence of blood in the feces were monitored and used to assess the disease activity index (DAI). After 62 days, the mice were sacrificed to evaluate the presence of intestinal polyps and dysplastic damage by histologic sections. Cyclomodulin-harboring E. coli colonized the mice; these mice exhibited weight loss and watery diarrhea, and isolated normal-weight E. coli had a higher DAI. Polyps were observed in mice infected with cyclomodulin-harboring E. coli in the ileum but to a greater extent in obese isolates. E. coli isolated from CRC showed more significant endothelial damage associated with dysplasia in the ileum in equal proportions from obese and normal-weight isolates. In conclusion, E. coli harboring cyclomodulins isolated from CRC, obesity, or normal weight can cause dysplastic damage in the ileum of mice and may be a risk factor for CRC development.

Previous studies have revealed that a high-fat diet (HFD) promotes the progression of colorectal cancer (CRC) in close association with disturbances in the intestinal flora and metabolic disorders. Xianglian pill (XLP) is a well-established traditional prescription with unique advantages in controlling intestinal flora imbalance and inflammation. However, its therapeutic effects on HFD-related CRC remain largely unknown.

The primary objective of this research was to investigate the anticancer mechanism of XLP in countering HFD-related CRC.

The protective effect of XLP was evaluated using azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced CRC model of mice exposed to a HFD. The degree of colorectal carcinogenesis, including body weight, colon length, and histopathology, was measured in mice treated with XLP and untreated mice. The effect of XLP on gut microbiota and its metabolites was detected using 16S rDNA and liquid chromatography/mass spectrometry analysis. Furthermore, a "pseudo-sterile" mouse model was constructed using antibiotics (Abx) to verify whether the gut microbiota and metabolites play a role in the pathogenesis of CRC.

XLP inhibited colorectal tumorigenesis in a dose-dependent fashion. Our findings also highlighted that XLP protected the integrity of the intestinal barrier by reducing the expression of pro-inflammatory cytokines, such as IL-6 and TNF-α, as well as the infiltration of pro-inflammatory macrophages. Mechanistically, XLP inhibited the TLR4/MyD88 pathway. Notably, the XLP treatment increased the proportion of probiotics (particularly Akkermansia) and significantly reduced fecal deoxycholic acid (DCA), a microbiota-derived metabolite of bile acids (BA) closely related to Muribaculaceae. Furthermore, after Abx treatment, XLP showed no clear antitumor effects on CRC. Simultaneously, DCA-supplemented feedings promoted colorectal tumorigenesis and provoked obvious colonic inflammation, M1 macrophage infiltration, and colonic injury. In vitro, the results of RAW-264.7 macrophages and normal intestinal epithelial cells treated with DCA corroborated our in vivo findings, demonstrating consistent patterns in inflammatory responses and intestinal barrier protein expression.

Our findings suggest that XLP inhibits colorectal cancer associated with HFD via inactivating TLR4/MyD88 by remodeling gut microbiota composition and BA metabolism.

The intestine is populated by a complex and dynamic assortment of microbes, collectively called gut microbiota, that interact with the host and contribute to its metabolism and physiology. Diet is considered a key regulator of intestinal microbiota, as ingested nutrients interact with and shape the resident microbiota composition. Furthermore, recent studies underscore the interplay of dietary and microbiota-derived nutrients, which directly impinge on intestinal stem cells regulating their turnover to ensure a healthy gut barrier. Although advanced sequencing methodologies have allowed the characterization of the human gut microbiome, mechanistic studies assessing diet-microbiota-host interactions depend on the use of genetically tractable models, such as Drosophila melanogaster. In this review, we first discuss the similarities between the human and fly intestines and then we focus on the effects of diet and microbiota on nutrient-sensing signaling cascades controlling intestinal stem cell self-renewal and differentiation, as well as disease. Finally, we underline the use of the Drosophila model in assessing the role of microbiota in gut-related pathologies and in understanding the mechanisms that mediate different whole-body manifestations of gut dysfunction.

Colorectal cancer (CRC) is characterized by its heterogeneity and complex metastatic mechanisms, presenting significant challenges in treatment and prognosis. This study aimed to unravel the intricate interplay between the gut microbiota and metabolic alterations associated with CRC metastasis. By employing high-throughput sequencing and advanced metabolomic techniques, we identified distinct patterns in the gut microbiome and fecal metabolites across different CRC metastatic sites. The differential gene analysis highlighted significant enrichment in biological processes related to immune response and extracellular matrix organization, with key genes playing roles in the complement and clotting cascades, and staphylococcus aureus infections. Protein-protein interaction networks further elucidated the potential mechanisms driving CRC spread, emphasizing the importance of extracellular vesicles and the PPAR signaling pathway in tumor metastasis. Our comprehensive microbiota analysis revealed a relatively stable alpha diversity across groups but identified specific bacterial genera associated with metastatic stages. Metabolomic profiling using OPLS-DA models unveiled distinct metabolic signatures, with differential metabolites enriched in pathways crucial for cancer metabolism and immune modulation. Integrative analysis of the gut microbiota and metabolic profiles highlighted significant correlations, suggesting a complex interplay that may influence CRC progression and metastasis. These findings offer novel insights into the microbial and metabolic underpinnings of CRC metastasis, paving the way for innovative diagnostic and therapeutic strategies targeting the gut microbiome and metabolic pathways.

Inflammation induces tumor formation and plays a crucial role in tumor progression and prognosis. KCNK6, by regulating K(+) efflux to reduce NLRP3 Inflammasome-induced lung injury, relaxes the aorta. This study aims to elucidate the effects and biological mechanism of KCNK6 in inflammation-associated carcinogenesis, which may be essential for colon homeostasis and the defense system. To induce colitis, mice were given 3.0% Dextran Sodium Sulfate (DSS) in their drinking water for 7 days. The Azoxymethane (AOM) +DSS method was used to induce colon cancer in the mice model. Bone marrow-derived macrophages (BMDM) from Kcnk6-/- mice, AW264.7 cells, and human colon cancer HCT116 and Caco2 cells were used as in vitro models. The loss of Kcnk6 prevented spontaneous colitis and restored mucosal integrity and homeostatic molecules. Additionally, the loss of Kcnk6 reduced the severity of AOM/DSS-induced carcinogenesis. Kcnk6 promoted cell viability and proliferation in HCT-116 or Caco-2 cells. The loss of Kcnk6 inhibited the levels of inflammatory factors in BMDM cells. Kcnk6 accelerated potassium channel activity, inducing NLRP3 inflammasome activation. METTL3-mediated m6A modification increased Kcnk6 stability in a YTHDF2-dependent manner. Histone lactylation activated the transcription of YTHDF2/Kcnk6. Our study revealed the important role of Kcnk6 in inflammation-associated carcinogenesis progression. The m6A methyltransferase METTL3 and histone lactylation increased Kcnk6 stability in a YTHDF2-dependent manner, providing a potential strategy for inflammation-associated carcinogenesis or colorectal cancer therapy.

Intestinal inflammation modifies host physiology to promote the occurrence of colorectal cancer (CRC), as seen in colitis-associated CRC. Gut microbiota is crucial in cancer progression, primarily by inducing intestinal chronic inflammatory microenvironment, leading to DNA damage, chromosomal mutation, and alterations in specific metabolite production. Therefore, there is an increasing interest in microbiota-based prevention and treatment strategies, such as probiotics, prebiotics, microbiota-derived metabolites, and fecal microbiota transplantation. This review aims to provide valuable insights into the potential correlations between gut microbiota and colitis-associated CRC, as well as the promising microbiota-based strategies for colitis-associated CRC.

Diet plays a critical role in shaping the gut microbiome, which in turn regulates molecular activities in the colonic mucosa. The state and composition of the gut microbiome are key factors in the development of colorectal cancer. An altered gut microbiome, linked to weakened immune responses and the production of carcinogenic substances, is a significant contributor to colorectal cancer pathogenesis. Dietary changes that involve low-fiber and phytomolecule intake, coupled with higher consumption of red meat, can raise the risk of colorectal cancer. Salutary filaments, which reach the colon undigested, are metabolized by the gut microbiome, producing short-chain fatty acids. Short-chain fatty acids possess beneficial anti-inflammatory and antiproliferative properties that promote colon health. A well-balanced microbiome, supported by beneficial fibers and phytochemicals, can regulate the activation of proto-oncogenes and oncogenic pathways, thereby reducing cell proliferation. Recent research suggests that an overabundance of specific microbes, such as Fusobacterium nucleatum, may contribute to adverse changes in the colonic mucosa. Positive lifestyle adjustments have been demonstrated to effectively inhibit the growth of harmful opportunistic organisms. Synbiotics, which combine probiotics and prebiotics, can protect the intestinal mucosa by enhancing immune responses and decreasing the production of harmful metabolites, oxidative stress, and cell proliferation. This narrative review provides a concise understanding of evolving evidence regarding how diet influences the gut microbiome, leading to the restoration of the colonic epithelium. It underscores the importance of a healthy, plant-based diet and associated supplements in preventing colorectal cancer by enhancing gut microbiome health.

Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical and molecular characteristics of colon versus rectal cancers, underscoring tumor location's importance in treatment approaches. This article provides a comprehensive review of our current understanding of CRC epidemiology, risk factors, molecular pathogenesis, and management strategies. We also present the intricate cellular architecture of colonic crypts and their roles in intestinal homeostasis. Colorectal carcinogenesis multistep processes are also described, covering the conventional adenoma-carcinoma sequence, alternative serrated pathways, and the influential Vogelstein model, which proposes sequential APC, KRAS, and TP53 alterations as drivers. The consensus molecular CRC subtypes (CMS1-CMS4) are examined, shedding light on disease heterogeneity and personalized therapy implications.

The process of drug discovery and pre-clinical testing is currently inefficient, expensive, and time-consuming. Most importantly, the success rate is unsatisfactory, as only a small percentage of tested drugs are made available to oncological patients. This is largely due to the lack of reliable models that accurately predict drug efficacy and safety. Even animal models often fail to replicate human-specific pathologies and human body's complexity. These factors, along with ethical concerns regarding animal use, urge the development of suitable human-relevant, translational in vitro models.

An expanding body of research indicates a correlation between the gut microbiota and various diseases. Metabolites produced by the gut microbiota act as mediators between the gut microbiota and the host, interacting with multiple systems in the human body to regulate physiological or pathological functions. However, further investigation is still required to elucidate the underlying mechanisms. One such metabolite involved in choline metabolism by gut microbes is trimethylamine (TMA), which can traverse the intestinal epithelial barrier and enter the bloodstream, ultimately reaching the liver where it undergoes oxidation catalyzed by flavin-containing monooxygenase 3 (FMO3) to form trimethylamine N-oxide (TMAO). While some TMAO is eliminated through renal excretion, remaining amounts circulate in the bloodstream, leading to systemic inflammation, endoplasmic reticulum (ER) stress, mitochondrial stress, and disruption of normal physiological functions in humans. As a representative microbial metabolite originating from the gut, TMAO has significant potential both as a biomarker for monitoring disease occurrence and progression and for tailoring personalized treatment strategies for patients. This review provides an extensive overview of TMAO sources and its metabolism in human blood, as well as its impact on several major human diseases. Additionally, we explore the latest research areas related to TMAO along with future directions.

Acute appendicitis (AA) is one of the most prevalent acute abdominal diseases and appendectomy is the definitive treatment of appendicitis. However, whether appendicitis and appendectomy cause colorectal cancer (CRC) is controversial. The results of observational studies are contradictory, but randomized controlled trials (RCT) cannot be conducted.

Data of appendectomy, AA, and CRC were obtained from the IEU Open GWAS project. We selected several Genome-wide association studies (GWAS) summary statistics for CRC: statistics for colon cancer (CC) were obtained from MRC-IEU and Neale lab, respectively; statistics for rectum cancer (RC) were obtained from MRC-IEU and FinnGen, respectively; statistics for CRC were provided by Sakaue S et al. Mendelian randomization (MR) was used to evaluate the causal relationships between exposure and outcomes. Inverse variance weighting (IVW) was the most important analysis method. Meta-analysis was used to summarize the results of IVW to increase the reliability and sensitivity analysis was used to evaluate the robustness of the results.

According to the results of IVW, appendectomy did not increase risk of CC: MRC-IEU (OR:1.009, 95%CI:0.984-1.035, P=0.494), Neale lab (OR:1.016, 95%CI:0.993-1.040, P=0.174); Appendectomy also did not increase risk of RC: MRC-IEU(OR:0.994, 95%CI:0.974-1.014, P=0.538), FinnGen(OR:2.791, 95%CI:0.013-580.763, P=0.706); Appendectomy also did not increase risk of CRC: Sakaue S(OR:1.382, 95%CI:0.301-6.352, P=0.678). Appendicitis did not increase risk of CC: MRC-IEU(OR:1.000, 95%CI:0.999-1.001, P=0.641), Neale lab(OR:1.000, 95%CI:1.000-1.001, P=0.319); Appendicitis also did not increase risk of RC: MRC-IEU(OR:1.000, 95%CI:0.999-1.000, P=0.361), FinnGen(OR:0.903, 95%CI:0.737-1.105, P=0.321); Appendicitis also did not increase risk of CRC: Sakaue S (OR:1.018, 95%CI:0.950-1.091, P=0.609). The results of Meta-analysis also showed appendectomy (P=0.459) and appendicitis (P=0.999) did not increase the risk of CRC.

Appendectomy and appendicitis do not increase the risk of colorectal cancer. More clinical trials are needed in the future to verify the causal relationships.

Activation of Gasdermin D (GSDMD) results in its cleavage, oligomerization, and subsequent formation of plasma membrane pores, leading to a form of inflammatory cell death denoted as pyroptosis. The roles of GSDMD in inflammation and immune responses to infection are well documented. However, whether GSDMD also plays a role in sporadic cancer development, especially that in the gut epithelium, remains unknown. Here, we show that GSDMD is activated in colorectal tumors of both human and mouse origins. Ablation of GSDMD in a mouse model of sporadic colorectal cancer resulted in reduced tumor formation in the colon and rectum, suggesting a tumor-promoting role of the protein in the gut. Both antibiotic-mediated depletion of gut microbiota and pharmacological inhibition of NLRP3 inflammasome reduced the activation of GSDMD. Loss of GSDMD resulted in reduced infiltration of immature myeloid cells, and increased numbers of macrophages in colorectal tumors. Activation of GSDMD is also accompanied by the aggregation of the endosomal sorting complex required for transport (ESCRT) membrane repair proteins on the membrane of colorectal tumor cells, suggesting that active membrane repairment may prevent pyroptosis induced by the formation of GSDMD pore in tumor cells. Our results show that gut microbiota/NLRP3-mediated activation of GSDMD promotes the development of colorectal tumors, and supports the use of NLRP3 inhibitors to treat colon cancer.

Diagnosing gastrointestinal (GI) disorders, which affect parts of the digestive system such as the stomach and intestines, can be difficult even for experienced gastroenterologists due to the variety of ways these conditions present. Early diagnosis is critical for successful treatment, but the review process is time-consuming and labor-intensive. Computer-aided diagnostic (CAD) methods provide a solution by automating diagnosis, saving time, reducing workload, and lowering the likelihood of missing critical signs. In recent years, machine learning and deep learning approaches have been used to develop many CAD systems to address this issue. However, existing systems need to be improved for better safety and reliability on larger datasets before they can be used in medical diagnostics. In our study, we developed an effective CAD system for classifying eight types of GI images by combining transfer learning with an attention mechanism. Our experimental results show that ConvNeXt is an effective pre-trained network for feature extraction, and ConvNeXt+Attention (our proposed method) is a robust CAD system that outperforms other cutting-edge approaches. Our proposed method had an area under the receiver operating characteristic curve of 0.9997 and an area under the precision-recall curve of 0.9973, indicating excellent performance. The conclusion regarding the effectiveness of the system was also supported by the values of other evaluation metrics.

The role of appendectomy in the pathogenesis of colorectal cancer (CRC) is a recent topic of contention. Given that appendectomy remains one of the most commonly performed operations and a first-line management strategy of acute appendicitis, it is inherently crucial to elucidate the association between prior appendectomy and subsequent development of CRC, as there may be long-term health repercussions. In this review, we summarize the data behind the relationship of CRC in post-appendectomy patients, discuss the role of the microbiome in relation to appendectomy and CRC pathogenesis, and provide an appraisal of our current understanding of the function of the appendix. We seek to piece together the current landscape surrounding the microbiome and immunological changes in the colon post-appendectomy and suggest a direction for future research involving molecular, transcriptomic, and immunologic analysis to complement our current understanding of the alterations in gut microbiome.

Intratumoral microbiota has become research hotspots, and emerges as a non-negligent new component of tumor microenvironments (TME), due to its powerful influence on tumor initiation, metastasis, immunosurveillance and prognosis despite in low-biomass. The accumulations of microbes, and their related components and metabolites within tumor tissues, endow TME with additional pluralistic features which are distinct from the conventional one. Therefore, it's definitely necessary to comprehensively delineate the sophisticated landscapes of tumor microbe microenvironment, as well as their functions and related underlying mechanisms. Herein, in this review, we focused on the fields of tumor microbe microenvironment, including the heterogeneity of intratumor microbiota in different types of tumors, the controversial roles of intratumoral microbiota, the basic features of tumor microbe microenvironment (i.e., pathogen-associated molecular patterns (PAMPs), typical microbial metabolites, autophagy, inflammation, multi-faceted immunomodulation and chemoresistance), as well as the multidisciplinary approach-based intervention of tumor microbiome for cancer therapy by applying wild-type or engineered live microbes, microbiota metabolites, antibiotics, synthetic biology and rationally designed biomaterials. We hope our work will provide valuable insight to deeply understand the interplay of cancer-immune-microbial, and facilitate the development of microbes-based tumor-specific treatments.

Colorectal cancer (CRC) is a worldwide health concern. Chronic inflammation is a risk factor for CRC, and interleukin-6 (IL-6) plays a pivotal role in this process. Arginine-specific mono-ADP-ribosyltransferase-1 (ART1) positively regulates inflammatory cytokines. ART1 knockdown reduces the level of glycoprotein 130 (gp130), a key transducer in the IL-6 signalling pathway. However, the relationship between ART1 and IL-6 and the resulting effects on IL-6-induced proliferation in CRC cells remain unclear. The aims of this study were to investigate the effects of ART1 knockdown on IL-6-induced cell proliferation in vitro and use an in vivo murine model to observe the growth of transplanted tumours. The results showed that compared with the control, ART1-sh cancer cells induced by IL-6 exhibited reduced viability, a lower rate of colony formation, less DNA synthesis, decreased protein levels of gp130, c-Myc, cyclin D1, Bcl-xL, and a reduced p-STAT3/STAT3 ratio (P < 0.05). Moreover, mice transplanted with ART1-sh CT26 cells that had high levels of IL-6 displayed tumours with smaller volumes (P < 0.05). ART1 and gp130 were colocalized in CT26, LoVo and HCT116 cells, and their expression was positively correlated in human CRC tissues. Overall, ART1 may serve as a promising regulatory factor for IL-6 signalling and a potential therapeutic target for human CRC.

Obesity has been positively associated with most molecular subtypes of colorectal cancer (CRC); however, the magnitude and the causality of these associations is uncertain.

We used Mendelian randomization (MR) to examine potential causal relationships between body size traits (body mass index [BMI], waist circumference, and body fat percentage) with risks of Jass classification types and individual subtypes of CRC (microsatellite instability [MSI] status, CpG island methylator phenotype [CIMP] status, BRAF and KRAS mutations). Summary data on tumour markers were obtained from two genetic consortia (CCFR, GECCO).

A 1-standard deviation (SD:5.1 kg/m2) increment in BMI levels was found to increase risks of Jass type 1MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype (odds ratio [OR]: 2.14, 95% confidence interval [CI]: 1.46, 3.13; p-value = 9 × 10-5) and Jass type 2non-MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype CRC (OR: 2.20, 95% CI: 1.26, 3.86; p-value = 0.005). The magnitude of these associations was stronger compared with Jass type 4non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-wildtype CRC (p-differences: 0.03 and 0.04, respectively). A 1-SD (SD:13.4 cm) increment in waist circumference increased risk of Jass type 3non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-mutated (OR 1.73, 95% CI: 1.34, 2.25; p-value = 9 × 10-5) that was stronger compared with Jass type 4 CRC (p-difference: 0.03). A higher body fat percentage (SD:8.5%) increased risk of Jass type 1 CRC (OR: 2.59, 95% CI: 1.49, 4.48; p-value = 0.001), which was greater than Jass type 4 CRC (p-difference: 0.03).

Body size was more strongly linked to the serrated (Jass types 1 and 2) and alternate (Jass type 3) pathways of colorectal carcinogenesis in comparison to the traditional pathway (Jass type 4).

Cancer Research UK, National Institute for Health Research, Medical Research Council, National Institutes of Health, National Cancer Institute, American Institute for Cancer Research, Brigham and Women's Hospital, Prevent Cancer Foundation, Victorian Cancer Agency, Swedish Research Council, Swedish Cancer Society, Region Västerbotten, Knut and Alice Wallenberg Foundation, Lion's Cancer Research Foundation, Insamlingsstiftelsen, Umeå University. Full funding details are provided in acknowledgements.

The gut microbiota has become one of the main risk factors for the formation and development of colorectal cancer (CRC). CRC intensification may be due to the microbial pathogens' colonization and their released metabolites. Here, we analyzed Bacteroidetes and Clostridia bacteria in CRC patients and studied bacterial metabolome in cancerous tissues compared to their adjacent normal tissues.

The population of selected bacteria in biopsy specimens of 30 patients with CRC was studied by RT-qPCR. The mutagenicity and cytotoxicity effects of microbiota metabolites were evaluated by Ames test and MTT Assay, respectively. Moreover, gene expression in carcinogenic pathways was studied by RT-qPCR, and genes with different expressions in tumor and non-tumor tissues were diagnosed. Based on microbiota analysis, the relative abundance of Clostridia and C. difficile was significantly higher in CRC tissue, whereas C. perfringens showed higher relative abundance in normal tissue. AIMES test confirmed the proliferation and mutagenicity effects of the bacterial metabolites in CRC patients. Significant upregulation of C-Myc, GRB2, IL-8, EGFR, PI3K, and AKT and downregulation of ATM were observed in CRC samples compared to the control.

The influence of bacterial metabolites on inflammation and altered expression of genes in the cell signaling pathways was observed. The findings confirm the role gut microbiota composition and bacterial metabolites as key players in CRC onset and development.

This comprehensive review article delves into the critical role of the human microbiota in the development and management of endocrine-related diseases. We explore the complex interactions between the microbiota and the endocrine system, emphasizing the implications of microbiota dysbiosis for the onset and progression of various endocrine disorders. The review aims to synthesize current knowledge, highlighting recent advancements and the potential of novel therapeutic approaches targeting microbiota-endocrine interactions. Key topics include the impact of microbiota on hormone regulation, its role in endocrine pathologies, and the promising avenues of microbiota modulation through diet, probiotics, prebiotics, and fecal microbiota transplantation. We underscore the importance of this research in advancing personalized medicine, offering insights for more tailored and effective treatments for endocrine-related diseases.

Targeting multiple immune mechanisms may overcome therapy resistance and further improve cancer immunotherapy for humans. Here, we describe the application of virus-like vesicles (VLV) for delivery of three immunomodulators alone and in combination, as a promising approach for cancer immunotherapy. VLV vectors were designed to deliver single chain interleukin (IL)-12, short-hairpin RNA (shRNA) targeting programmed death ligand 1 (PD-L1), and a dominant-negative form of IL-17 receptor A (dn-IL17RA) as a single payload or as a combination payload. Intralesional delivery of the VLV vector expressing IL-12 alone, as well as the trivalent vector (designated CARG-2020) eradicated large established tumors. However, only CARG-2020 prevented tumor recurrence and provided long-term survival benefit to the tumor-bearing mice, indicating a benefit of the combined immunomodulation. The abscopal effects of CARG-2020 on the non-injected contralateral tumors, as well as protection from the tumor cell re-challenge, suggest immune-mediated mechanism of protection and establishment of immunological memory. Mechanistically, CARG-2020 potently activates Th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting inflammation. The ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy.

Age-related changes in the microbiome have been reported in previous studies; however, direct evidence for their association with frailty is lacking. Here, we introduce biological age based on gut microbiota (gAge), an integrated prediction model that integrates gut microbiota data from different perspectives with potential background factors for aging assessment. Simulation results show that, compared with a single model, the ensemble model can not only significantly improve the prediction accuracy, but also make full use of the data in unpaired samples. From this, we identified markers associated with age development and grouped markers into accelerated aging and mitigated aging according to their effect on the prediction. Importantly, the application of gAge to an elderly cohort with different frailty levels confirmed that gAge and its predictive residuals are closely related to the individual's health status and frailty stage, and age-related markers overlap significantly with disease and frailty characteristics. Furthermore, we applied the gAge prediction model to another independent cohort of the elderly population for aging assessment and found that gAge could effectively represent the aging population. Overall, our study explains the association between the gut microbiota and frailty, providing potential targets for the development of gut microbiota-based targeted intervention strategies for aging.

The interaction between the gut microbiota and invariant Natural Killer T (iNKT) cells plays a pivotal role in colorectal cancer (CRC). The pathobiont Fusobacterium nucleatum influences the anti-tumor functions of CRC-infiltrating iNKT cells. However, the impact of other bacteria associated with CRC, like Porphyromonas gingivalis, on their activation status remains unexplored. In this study, we demonstrate that mucosa-associated P. gingivalis induces a protumour phenotype in iNKT cells, subsequently influencing the composition of mononuclear-phagocyte cells within the tumor microenvironment. Mechanistically, in vivo and in vitro experiments showed that P. gingivalis reduces the cytotoxic functions of iNKT cells, hampering the iNKT cell lytic machinery through increased expression of chitinase 3-like-1 protein (CHI3L1). Neutralization of CHI3L1 effectively restores iNKT cell cytotoxic functions suggesting a therapeutic potential to reactivate iNKT cell-mediated antitumour immunity. In conclusion, our data demonstrate how P. gingivalis accelerates CRC progression by inducing the upregulation of CHI3L1 in iNKT cells, thus impairing their cytotoxic functions and promoting host tumor immune evasion.

Colorectal carcinoma (CRC) is the third most common cancer in terms of diagnosis and the second in terms of mortality. Recent studies have shown that various proteins, extracellular vesicles (i.e., exosomes), specific genetic variants, gene transcripts, cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and altered epigenetic patterns, can be used to detect, and assess the prognosis of CRC. Over the last decade, a plethora of conventional methodologies (e.g., polymerase chain reaction [PCR], direct sequencing, enzyme-linked immunosorbent assay [ELISA], microarray, in situ hybridization) as well as advanced analytical methodologies (e.g., microfluidics, electrochemical biosensors, surface-enhanced Raman spectroscopy [SERS]) have been developed for analyzing genetic and epigenetic biomarkers using both optical and non-optical tools. Despite these methodologies, no gold standard detection method has yet been implemented that can analyze CRC with high specificity and sensitivity in an inexpensive, simple, and time-efficient manner. Moreover, until now, no study has critically reviewed the advantages and limitations of these methodologies. Here, an overview of the most used genetic and epigenetic biomarkers for CRC and their detection methods are discussed. Furthermore, a summary of the major biological, technical, and clinical challenges and advantages/limitations of existing techniques is also presented.