Iron deficiency anemia (IDA) is associated with digestive system cancers (DSCs), but the causal relationship is poorly understood. This two-sample bidirectional Mendelian randomization (MR) study investigated the causal association between IDA and five types of DSCs.

This study pooled data from a genome-wide association study of IDA (6,087 cases and 211,115 controls of European ancestry) and DSCs. IVW, weighted median, weighted mode, and MR-Egger regression were used to assess causal associations between IDA and DSCs. Sensitivity analysis included Cochran's Q test for heterogeneity, MR-PRESSO for pleiotropy, and leave-one-out method for robustness.

The MR analysis used 12 single-nucleotide polymorphisms (SNPs) associated with IDA as instrumental variables (IVs). In contrast, the reverse MR analysis used 20 SNPs associated with the five types of DSC as IVs. Genetic predictions revealed no significant association between IDA and the risk of DSCs: (odds ratio [OR]: 1.00; 95% confidence interval [CI] [0.76, 1.31]; P = 0.979), esophageal (OR: 0.94; 95% CI [0.67, 1.31]; P = 0.699), pancreatic (OR: 1.14; 95% CI [0.68, 1.92]; P = 0.615), liver (OR: 1.12; 95% CI [0.51, 2.47]; P = 0.776), and stomach (OR: 1.04; 95% CI [0.71, 1.54]; P = 0.830) cancers. Reverse MR also indicated no causal association between DSC and IDA. MR-Egger regression showed minimal heterogeneity impact except for colorectal cancer (heterogeneity P = 0.002). MR-PRESSO identified no outliers.

The present MR analysis shows no causal associations between IDA and the risk of DSCs.

Vitamin D plays a crucial role in the regulation of the immune system, with immunomodulatory effects that are key in the prevention of colorectal cancer (CRC). Over the past decades, research has shown that this steroid hormone impacts much more than bone health, significantly influencing immune responses. Vitamin D enhances immune organ functions such as the spleen and lymph nodes, and boosts T-cell activity, which is essential in defending the body against tumors. Additionally, vitamin D mitigates inflammatory responses closely linked to cancer development, reducing the inflammation that contributes to CRC. It acts via vitamin D receptors (VDRs) expressed on immune cells, modulating immune responses. Adequate vitamin D levels influence gene expression related to inflammation and cell proliferation, inhibiting tumor development. Vitamin D also activates mechanisms that suppress cancer cell survival, proliferation, migration, and metastasis. Low levels of vitamin D have been associated with an increased risk of CRC, with deficiency correlating with higher disease incidence. Lifestyle factors, such as a diet high in red meat and calories but low in fiber, fruits, and vegetables, as well as physical inactivity, contribute significantly to CRC risk. Insufficient calcium and vitamin D intake are also linked to disease occurrence and poorer clinical outcomes. Maintaining optimal vitamin D levels and adequate dietary intake is crucial in preventing CRC and improving patient prognosis. This review explores the role of vitamin D in immune regulation and summarizes findings from randomized clinical trials assessing the effects of vitamin D supplementation on CRC outcomes.

Recent research has highlighted the complex relationship between gut microbiota, metabolic pathways, and nonalcoholic fatty liver disease (NAFLD) progression. Gut dysbiosis, commonly observed in NAFLD patients, impairs intestinal permeability, leading to the translocation of bacterial products like lipopolysaccharides, short-chain fatty acids, and ethanol to the liver. These microbiome-associated mechanisms contribute to intestinal and hepatic inflammation, potentially advancing NAFLD to NASH. Dietary habits, particularly those rich in saturated fats and fructose, can modify the microbiome composition, leading to dysbiosis and fatty liver development. Metabolomic approaches have identified unique profiles in NASH patients, with specific metabolites like ethanol linked to disease progression. While bariatric surgery has shown promise in preventing NAFLD progression, the role of gut microbiome and metabolites in this improvement remains to be proven. Understanding these microbiome-related pathways may provide new diagnostic and therapeutic targets for NAFLD and NASH. A comprehensive review of current literature was conducted using multiple medical research databases, including PubMed, Scopus, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov, ScienceDirect, Medline, ProQuest, and Google Scholar. The review focused on studies that examine the relationship between gut microbiota composition, metabolic pathways, and NAFLD progression. Key areas of interest included microbial dysbiosis, endotoxin production, and the influence of diet on gut microbiota. The analysis revealed that gut dysbiosis contributes to NAFLD through several mechanisms, diet significantly influences gut microbiota composition, which in turn affects liver function through the gut-liver axis. High-fat diets can lead to dysbiosis, altering microbial metabolic activities and promoting liver inflammation. Specifically, gut microbiota-mediated generation of saturated fatty acids, such as palmitic acid, can activate liver macrophages and increase TNF-α expression, contributing to NASH development. Different dietary components, including cholesterol, fiber, fat, and carbohydrates, can modulate the gut microbiome and influence NAFLD progression. This gut-liver axis plays a crucial role in maintaining immune homeostasis, with the liver responding to gut-derived bacteria by activating innate and adaptive immune responses. Microbial metabolites, such as bile acids, tryptophan catabolites, and branched-chain amino acids, regulate adipose tissue and intestinal homeostasis, contributing to NASH pathogenesis. Additionally, the microbiome of NASH patients shows an elevated capacity for alcohol production, suggesting similarities between alcoholic steatohepatitis and NASH. These findings indicate that targeting the gut microbiota may be a promising approach for NASH treatment and prevention. Recent research highlights the potential of targeting gut microbiota for managing nonalcoholic fatty liver disease (NAFLD). The gut-liver axis plays a crucial role in NAFLD pathophysiology, with dysbiosis contributing to disease progression. Various therapeutic approaches aimed at modulating gut microbiota have shown promise, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and dietary interventions. Probiotics have demonstrated efficacy in human randomized controlled trials, while other interventions require further investigation in clinical settings. These microbiota-targeted therapies may improve NAFLD outcomes through multiple mechanisms, such as reducing inflammation and enhancing metabolic function. Although lifestyle modifications remain the primary recommendation for NAFLD management, microbiota-focused interventions offer a promising alternative for patients struggling to achieve weight loss targets.

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

Most studies suggest that B vitamins can reduce the risk of colorectal cancer (CRC), and research in this field has been growing. Focusing on 2617 articles in the field, this study used CiteSpace and VOSviewer software to evaluate the contributions of various countries/regions, institutions, authors, and journals. The United States and Harvard University were identified as the most productive nation and institution, respectively, with Edward L. Giovannucci (Harvard) being the top contributor. Cancer Epidemiology Biomarkers & Prevention was recognized as the leading journal. Through the analysis of keywords and citations, we found that the potential of B vitamins (B1, B2, B6, B9, and B12) in the prevention and treatment of CRC and their mechanisms including regulation of gene expression, anti-inflammatory and antioxidant, and modulation of gut microenvironment are hot topics of research in this field. Burst detection analysis further revealed that the application of nanoparticle-based targeted drug delivery systems (such as folate-conjugated nanocarriers) in the treatment of CRC represents both a current hotspot and a future trend. This study offers a comprehensive overview of the field, highlights research hotspots and trends, and offers valuable information for researchers to further grasp the research direction.

Colorectal cancer (CRC) is the world's third most frequent cancer, and both its incidence and fatality rates are rising. Despite various therapeutic approaches, neither its mortality rate nor its recurrence frequency has decreased significantly. Additionally, conventional treatment approaches, such as chemotherapy and radiotherapy, have several side effects and risks for patients with CRC. Accordingly, the need for alternative and effective treatments for CRC patients is critical. Immunotherapy that utilizes dendritic cells (DCs) harnesses the patient's immune system to combat cancer cells effectively. DCs are the most potent antigen-presenting cells (APCs), which play a vital role in generating anti-cancer T cell responses. A significant barrier to the immune system's ability to eliminate CRC is the establishment of a potent immunosuppressive tumor milieu by malignant cells. Since DCs are frequently defective in this milieu, the tumor setting significantly reduces the effectiveness of DC-based therapy. Determining central mechanisms contributing to tumor growth by unraveling and comprehending the interaction between CRC tumor milieu and DCs may lead to new therapeutic approaches. This study aims to review DC biology and discuss its role in T-cell-mediated anti-tumor immunity, as well as to highlight the immunosuppressive effects of the CRC tumor milieu on the function of DCs. We will also highlight the tumor microenvironment (TME)-related factors that interfere with DC function as a possible therapeutic target to enhance DC-based cell therapy efficacy.

Non-esophageal eosinophilic gastrointestinal diseases (non-EoE EGIDs) are allergic conditions where Th-2-predominant inflammation causes symptoms related to gastrointestinal tract dysfunction. No studies have reported the incidence of non-EoE EGIDs. In addition, little is known about the influence of lifestyle factors on the condition.

We used a large health claim database from January 2005 to September 2022. Non-EoE EGIDs cases were identified on the basis of the International Classification of Diseases-tenth Revision code, K52.8. The incidence and prevalence of non-EoE EGIDs were estimated by Poisson and binomial distribution, respectively. For each case, 10 controls were randomly selected for a nested case-control study to identify potential risk factors of non-EoE EGIDs.

Of 15,200,895 individuals, 1,368 new cases of non-EoE EGIDs were identified. The incidence and prevalence of non-EoE EGIDs in 2022 were 3.07 (95% CI 2.67-3.52) per 100,000 person-years and 17.23 (95% CI 16.38-18.11) per 100,000 individuals, respectively, which were approximately 6 and 9 times higher than those in 2010. Allergic rhinitis (OR 1.63 (95% CI 1.16-2.29), p = 0.005), chronic sinusitis (OR 2.41 (95% CI 1.58-3.66), p < 0.001), and urticaria (OR 2.32 (95% CI 1.45-3.70), p < 0.001) were related to an increased risk of adult non-EoE EGIDs. Whilst atopic dermatitis (OR 2.28 (95% CI 1.35-3.86), p = 0.006) and the perinatal factors (OR 3.68 (95% CI 1.13-12.02), p = 0.031) were associated with an increased risk of pediatric non-EoE EGIDs. No association was seen with lifestyle factors such as obesity, smoking and alcohol consumption.

The incidence and prevalence of non-EoE EGIDs have increased over the past two decades.

The role of vitamin D in the prevention of colorectal cancer (CRC) has been the focus of research, but the results of relevant studies are not entirely consistent. While most studies indicate that vitamin D has a protective effect against CRC, there are also research reports stating that at high serum levels, there is no significant association between vitamin D and CRC, or even an increased risk. Additionally, there are still differences in the recommended serum 25-hydroxyvitamin D [25(OH)D] concentrations among various guidelines or committees. This study examined the association between serum 25-hydroxyvitamin D concentrations and the risk of CRC in US adults.

This study included 43,678 adult participants from the National Health and Nutrition Examination Survey (NHANES) 2001-2018, and logistic regression modelling was used to examine the association between serum 25(OH)D concentrations and the risk of CRC. We grouped participants according to the classification criteria of the various guidelines available for vitamin D, and controlled for confounding using a multi-model strategy, adjusting for key covariates such as gender, age, race, education level, marital status, family income to poverty ratio (PIR), body mass index (BMI), smoking habits, drinking habits, diabetes, hypertension, dyslipidemia, calcium intake, and total folate intake. We also performed trend tests to evaluate the linear relationship between serum 25(OH)D concentrations and CRC risk, used restricted cubic spline (RCS) plots to assess the dose-response relationship, and conducted further subgroup analyses with interaction tests to examine potential variations in the association across different population groups. We focused on the association between serum 25(OH)D concentration ≤ 75 nmol/L and CRC, again using multivariable logistic regression with a multi-model strategy and RCS plots.

A total of 43,382 participants without CRC and 296 participants with CRC were included in this study. In the fully adjusted model, participants with serum 25(OH)D < 50 nmol/L had more than twice the risk of developing CRC compared to those with levels of 50-< 75 nmol/L (<30 nmol/L: Odds Ratio [OR] = 2.038, 95% Confidence Interval [CI]: 1.011-4.109; 30- < 50 nmol/L: OR = 2.090, 95% CI: 1.361-3.211). The negative correlation between serum 25(OH)D concentration and the risk of CRC was significant when serum 25(OH)D concentration was ≤ 75 nmol/L (P < 0.001). Each 1 nmol/L increase in serum 25(OH)D concentration was associated with an approximately 2.3% reduction in the risk of CRC (95% CI: 0.964-0.990).

Our findings indicate a strong inverse association between serum 25(OH)D concentrations and the risk of CRC, particularly when levels are ≤75 nmol/L. Maintaining serum 25(OH)D above 75 nmol/L is associated with a lower CRC risk and may serve as a cost-effective preventive strategy. Public health measures, including routine vitamin D screening in high-risk populations and targeted supplementation, could further support CRC prevention efforts.

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

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

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

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

Colorectal cancer is recognized as the third most prevalent malignant tumor globally. The recommended treatment modalities, including surgery, radiotherapy, and chemotherapy, are frequently associated with severe side effects and high recurrence rates. Cancer experts are actively engaged in a global pursuit of safer and more efficacious treatment strategies for colorectal cancer (CRC). Insect medicine, a unique subset of traditional Chinese medicine, is characterized by their broad spectrum of therapeutic effects, which include antibacterial, anticoagulant, antithrombotic, and sedative actions. Insects are enriched with proteins, peptides, and amino acids. These compounds exhibit pharmacological activities, including anti-tumor effects, inhibition of cancer cell proliferation, induction of apoptosis in cancer cells, anti-inflammatory properties, and immunomodulation. Recent studies have revealed that certain traditional Chinese insect medicines, such as Bombyx Batryticatus, Tubiechong, and Aspongopus chinensis Dalls, demonstrate outstanding therapeutic efficacy in the treatment of CRC. The anti-CRC actions of these insect medicines are potentially mediated through mechanisms involving the Hedgehog and Wnt/β-catenin signaling pathways, as well as immunomodulatory effects. Consequently, these insect medicines are proposed as a potential strategy for CRC treatment.

Colorectal cancer (CRC) is a malignant tumor that originates from the epithelial cells of the colon and rectum. Global epidemiological data shows that in 2020, the incidence and mortality rate of CRC ranked third and second, respectively, posing a serious threat to people's health and lives. The factors influencing CRC are numerous and can be broadly categorized as modifiable and non-modifiable based on whether they can be managed or intervened upon. Non-modifiable factors include age, gender, family history, among others. Among the modifiable factors, dietary habits and behavioral practices are the main intervention measures that people can take to prevent CRC. Numerous studies indicate that a high intake of red and processed meats, fats, as well as habits such as smoking, alcohol consumption, and prolonged sitting, increase the risk of developing CRC. Conversely, consuming ample vegetables, fruits, high dietary fiber, and engaging in moderate regular exercise may reduce the risk of CRC. This article primarily discusses the impact of dietary habits and behavioral practices on the occurrence and development of CRC, along with possible mechanisms, laying the foundation and providing direction for the prevention and control of CRC occurrence and development.

Alteration of the gut microbiota (GM) is associated with various diseases, including colorectal cancer (CRC). With the development of next-generation sequencing techniques, metagenomic sequencing, along with metabolic function and antibiotic-resistant gene analyses, has been used to investigate differences in GM between CRC patients and healthy controls. Fecal samples were obtained from seven CRC patients and six healthy subjects, and the sequencing data were analyzed for similarity, a-diversity, principal component analysis (PCA), and linear discriminant analyses (LDA). Regarding Actinobacteria, 3 orders, 5 families, 9 genera, and 19 species were identified with no differences between the CRC and control groups, while the levels of Bifidobacterium bifidum and Bifidobacterium dentium were higher, and the level of Bifidobacterium breve was lower in the CRC group compared to the healthy controls (p = 0.053). Otherwise, 2 genera (Leuco-nostoc and Salmonella) and 7 species of bacteria (Parabacteroides merdae, Alistipes shahii, Alistipes finegoldii, Clostridium nexile, Salmonella enterica, unclassified Salmonella, Enterobacter cloacae) were found to be significantly differently distributed between CRC patients and healthy controls. PCA-LDA successfully classified these 2 groups with satisfactory accuracy (84.52% for metabolic function and 77.38% for resistant genes). These findings underscore the potential of GM as a diagnostic tool for CRC, offering a promising avenue for non-invasive screening and risk assessment. The identification of specific microbial signatures, particularly those linked to metabolic functions and resistance traits, could open new doors for understanding the role of the microbiome in CRC progression and treatment resistance.

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

Colorectal cancer (CRC) is the second deadliest carcinoma across the globe and has been known as a multi-factor induced-disease. Emerging research have demonstrated that bacterial colonization may contribute to the initiation and promotion of the CRC. The presence of Fusobacterium nucleatum (F. nucleatum) and Bacteroides fragilis (B. fragilis) in the gut is associated with the development of CRC. In this study, the prevalence of F. nucleatum and B. fragilis among CRC patients has been assessed worldwide through a systematic review and meta-analysis.

The extensive search was performed using "Fusobacterium nucleatum", "Bacteroides fragilis", "Colorectal cancer" and all relevant keywords. Then, a systematic paper screening was done following a comprehensive search in Embase, Web of Science, and PubMed databases while the time range was limited between the years 2000 and 2024. Afterwards, statistical analysis was performed utilizing the comprehensive meta-analysis (CMA) software (version 2.0, Biostat, USA).

According to the meta-analysis of prevalence studies, the prevalence of F. nucleatum among 19 countries and B. fragilis among 10 countries were indicated to be 38.9% (95% CI 33.7-44.3%) and 42.5% (95% CI 34.4-51.1%), respectively, among the CRC patients. It was then revealed that Asia had the highest prevalence of F. nucleatum while most of the B. fragilis isolates in CRC cases were reported in European countries. Moreover, the data suggested that the most common comorbidity observed among the CRC cases was diabetes.

Our results emphasized the high prevalence of F. nucleatum and B. fragilis in CRC patients. Based on this meta-analysis review, regulating the gut microbiota in CRC patients seemed to be a promising approach to improving the efficacy of CRC therapy.

Metabolic risks are significant factors associated with colorectal cancer. This study aimed to assess global, regional and national burden for CRC attributable to metabolic risks from 1990 to 2021 and to predict mortality by 2046.

Data from the Global Burden of Disease Study 2021 were used to quantify deaths, disability-adjusted life years (DALYs), and age-standardized rates of CRC due to metabolic risk factors, disaggregated by sex, age, region, country/territory, and sociodemographic index (SDI). The average annual percentage change (AAPC) was used to analyze temporal trends from 1990 to 2021. Metabolic risks include high fasting plasma glucose (FPG) and high body mass index (BMI). Future mortality trends up to 2046 were forecast using age-period-cohort models.

Globally, CRC deaths attributable to metabolic risks increased 2.47-fold, rising from 73,443 in 1990 to 181,689 in 2021. The global age-standardized mortality rates (ASMRs) and age-standardized rates of DALYs (ASDRs) of CRC attributable to high FPG and ASDRs attributable to high BMI increased from 1990 to 2021. The ASMRs and ASDRs of males was higher than that of females, with increasing trends. Central Europe had the highest ASMRs and ASDRs of CRC attributable to metabolic risks in 2021. Most regions and countries showed increasing trends in ASMR and ASDR for CRC due to metabolic risks, with Andean Latin America, Southeast Asia, and Cabo Verde increasing the most. High-SDI regions had the largest burden of CRC attributable to metabolic risks, while burden of other SDI regions have been significantly increased. A positive association was observed between SDI and age-standardized rates (ASMR: RFPG = 0.803, RBMI = 0.752; ASDR: RFPG = 0.812, RBMI = 0.756). By 2046, the ASMR of CRC attributable to high FPG was projected to remain stable and the ASMR due to high BMI was expected to see a slightly increase.

Colorectal cancer deaths and DALYs attributable to metabolic risk factors remain high, particularly in males and high-SDI regions. Further researches into the metabolic mechanisms of CRC and effective treatment strategies are needed.

Very early-onset colorectal cancer (EOCRC) was defined as CRC diagnosed before the age of 35 proposed by the latest EOCRC management guideline. Until now, the disease burden of very EOCRC has never been reported. This study aimed to explore the burden of very EOCRC across the past three decades.

We extracted the data from Global Burden of Disease Study to analyze the disease burden of very EOCRC. Risk factors for the burden of deaths and disability-adjusted life years (DALYs) due to very EOCRC were also explored in this study. Additionally, decomposition analysis and frontier analysis were also conducted.

Despite regional and gender variations, the global very EOCRC incidence cases increased from 21,874 (95 % UI: 20,386-23,470) to 41,545 (95 % UI: 37,978-45,523). Besides, the deaths cases also increased from 11,445 (95 % UI: 10,545-12,374) to 15,486 (95 % UI: 14,289-16,803), and the DALYs cases increased from 718,136 (95 % UI: 659,858-778,283) to 961,460 (95 % UI: 886,807-1,042,734). Decomposition analysis revealed the epidemiological change contributed most to the incidence burden of very EOCRC. Countries or regions with Sociodemographic Index (SDI) between 0.4 and 0.8 had greater disease burden improvement potential through frontier analysis. Diet low in milk, diet low in calcium, alcohol use, and high body-mass index were the main contributors to deaths and DALYs.

The increase in CRC burden among populations younger than 35 years globally requires vigilance from policy makers, physicians, and young individuals themselves, especially those regions experiencing faster growth burden of very EOCRC.

Lynch syndrome (LS)-associated colorectal cancer (CRC) always ascribes to pathogenic germline mutations in mismatch repair (MMR) genes. However, the penetrance of CRC varies among those with the same MMR gene mutation. Thus, we hypothesized that the gut microbiota is also involved in CRC development in LS families.

This prospective, observational study was performed from December 2020 to March 2023. We enrolled 72 individuals from 9 LS families across six provinces in China and employed 16S rRNA gene amplicon sequencing to analyze the fecal microbiota components among LS-related CRC patients (AS group), their spouses (BS group), mutation carriers without CRC (CS group), and non-mutation carriers (DS group) using alpha and beta diversity indices.

There were no apparent differences in age or gender among the four groups. Alpha and beta diversity indices exhibited no significant differences between the AS and BS groups, verifying the role of germline mutations in the occurrence of CRC in LS families. Beta diversity analysis exhibited significant differences between the AS and CS groups, revealing the importance of the gut microbiota for the occurrence of CRC in LS families. A greater difference (both alpha and beta diversity indices) was shown between the AS and DS groups, demonstrating the combined impact of the gut microbiota and genetic germline mutations on the occurrence of CRC in LS families. Compared with those in the CS and DS groups, we identified ten microbial genera enriched in the AS group, and one genus (Bacteroides) decreased in the AS group. Among the elevated genera in the AS group, Agathobacter, Coprococcus and Prevotellaceae_NK3B31_group were butyrate-producing genera.

This study found the development of CRC in the LS families can be attributed to the combined effects of gene germline mutations as well as the gut microbiota and provided novel insights into the prevention and treatment of CRC in the LS families.

The NIH policy on sex as biological variable (SABV) emphasized the importance of sex-based differences in precision oncology. Over 50% of clinically actionable oncology genes are sex-biased, indicating differences in drug efficacy. Research has identified sex differences in non-reproductive cancers, highlighting the need for comprehensive sex-based cancer data. We therefore developed OncoSexome, a multidimensional knowledge base describing sex-based differences in cancer (https://idrblab.org/OncoSexome/) across four key topics: antineoplastic drugs and responses (SDR), oncology-related biomarkers (SBM), risk factors (SRF) and microbial landscape (SML). SDR covers sex-based differences in 2051 anticancer drugs; SBM describes 12 551 sex-differential biomarkers; SRF illustrates 350 sex-dependent risk factors; SML demonstrates 1386 microbes with sex-differential abundances associated with cancer development. OncoSexome is unique in illuminating multifaceted influences of biological sex on cancer, providing both external and endogenous contributors to cancer development and describing sex-based differences for the broadest oncological classes. Given the increasing global research interest in sex-based differences, OncoSexome is expected to impact future precision oncology practices significantly.

This review provides a comprehensive overview of the recent advancements in research on ATF4 (Activating Transcription Factor 4) within the field of oncology. As a crucial transcription factor, ATF4 has garnered increasing attention for its role in cancer research. The review begins with an exploration of the regulatory mechanisms of ATF4, including its transcriptional control, post-translational modifications, and interactions with other transcription factors. It then highlights key research findings on ATF4's involvement in various aspects of tumor biology, such as cell proliferation, differentiation, apoptosis and survival, invasion and metastasis, and the tumor microenvironment. Furthermore, the review discusses the potential of targeting ATF4 as a novel therapeutic strategy for cancer treatment. It also explores how ATF4's interactions with existing anticancer drugs could inform the development of more effective therapeutic agents. By elucidating the role of ATF4 in tumor biology and its potential clinical applications, this review aims to provide new insights and strategies for cancer treatment.

Acyl urea compounds have garnered significant attention in cancer therapeutics, particularly for their potential effectiveness against cancers that predominantly affect women, such as breast and ovarian cancers. The paper presents a report on the investigation of acyl urea compounds that are reported to involve a multi-faceted approach, including synthetic chemistry, biological assays, and computational modeling. A wealth of information on acyl urea and its purported effects on cancer affecting women has been gathered from different sources and condensed to provide readers with a broad understanding of the role of acyl urea in combating cancer. Acylureas demonstrate promising results by selectively inhibiting key molecular targets associated with cancer progressions, such as EGFR, ALK, HER2, and the Wnt/β-catenin signaling pathway. Specifically, targeting acyl ureas impedes tumor proliferation and metastasis while minimizing harm to healthy tissues, offering a targeted therapeutic approach with reduced side effects compared to conventional chemotherapy. Continued research and clinical trials are imperative to optimize the efficacy and safety profiles of acylurea-based therapies and broaden their applicability across various cancer types. Acyl urea compounds represent a promising class of therapeutics for the treatment of cancers in women, particularly due to their ability to selectively inhibit key molecular targets involved in tumor growth and progression. The combination of synthetic optimization, biological evaluation, and computational modeling has facilitated the identification of several lead compounds with significant anticancer potential. This abstract explores the therapeutic mechanisms and targeted pathways of acyl ureas in combating these malignancies, which will be useful for future studies.

Gut microbiota plays an important role in multiple human physiological processes and an imbalance in it, including the species, abundance, and metabolites can lead to diseases. These enteric microorganisms modulate immune homeostasis by presenting a myriad of antigenic determinants and microbial metabolites. Medicinal and food homologous (MFH) plants, edible herbal materials for both medicine and food, are important parts of Traditional Chinese Medicine (TCM). MFH plants have drawn much attention due to their strong biological activity and low toxicity. However, the interplay of MFH and gut microbiota in rebalancing the immune homeostasis in combating diseases needs systematic illumination.

The review discusses the interaction between MFH and gut microbiota, including the effect of MFH on the major group of gut microbiota and the metabolic effect of gut microbiota on MFH. Moreover, how gut microbiota influences the immune system in terms of innate and adaptive immunity is addressed. Finally, the immunoregulatory mechanisms of MFH in regulation of host pathophysiology via gut microbiota are summarized.

Literature was searched, analyzed, and collected using databases, including PubMed, Web of Science, and Google Scholar using relevant keywords. The obtained articles were screened and summarized by the research content of MFH and gut microbiota in immune regulation.

The review demonstrates the interaction between MFH and gut microbiota in disease prevention and treatment. Not only do the intestinal microorganisms and intestinal mucosa constitute an important immune barrier of the human body, but also lymphoid tissue and diffused immune cells within the mucosa participate in the response of innate immunity and adaptive immunity. MFH modulates immune regulation by affecting intestinal flora, helps maintain the balance of the immune system and interfere with the occurrence and development of a broad category of diseases.

Being absorbed from the gastrointestinal tract, MFH can have profound effects on gut microbiota. In turn, the gut microbiota also actively participate in the bioconversion of complex constituents from MFH, which could further influence their physiological and pharmacological properties. The review deepens the understanding of the relationship among MFH, gut microbiota, immune system, and human diseases and further promotes the progression of additional relevant research.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that presents significant challenges in terms of treatment owing to a pronounced likelihood of recurrence and an elevated risk of cancer development, thereby imposing substantial risks on affected individuals. The gut microbiota of Firmicutes and Bacteroidetes (F/B) can affect diseases associated with IBD, which is also a risk factor for breast cancer. This review discusses the hazards associated with UC, highlights the existing disparities in UC-associated gut microbiome research, explores the concept of the F/B ratio and scrutinizes its correlation with UC. Moreover, the differences in the F/B ratios between healthy individuals and those with UC were thoroughly examined. These findings suggest that an elevated F/B ratio may promote the occurrence and progression of UC. Consequently, the F/B ratio may play a significant role in UC by influencing gut microbiota composition and inflammatory responses, suggesting that future research should focus on this ratio as a potential biomarker for disease progression and therapeutic targets in managing UC.

Early-onset colorectal cancer (EO-CRC) is becoming increasingly concerning due to its impact on individuals under 50 years old. We explored the burden of EO-CRC to provide information for planning effective management and prevention strategies.

We conducted secondary analyses to assess the burden of EO-CRC using data from GBD 2021.

The incidence, prevalence, deaths, disability-adjusted life years (DALYs) and their rates across 204 countries and territories were obtained from GBD 2021 database. The estimated annual percentage change (EAPC) calculation was used to assess temporal trends in these metrics. Additionally, we reported the proportion of DALYs attributable to risk factors and projected future disease burden till 2050.

The global number of new EO-CRC cases increased from 107,310 in 1990 to 211,890 in 2021. Both age-standardized incidence rate (ASIR) and prevalence rate (ASPR) of EO-CRC showed overall increases over the study period (ASIR: EAPC = 0.96 (0.9-1.02), ASPR: EAPC = 1.5 (1.44-1.55)). However, a decline in ASIR and ASPR was observed in 2020 and 2021. Males consistently showed higher EO-CRC indicators compared to females. Furthermore, projections indicated that deaths and DALYs cases are likely to fluctuate but generally increase by 2050, reaching 85,602 and 4,283,093, respectively.

The global impact of EO-CRC has increased significantly from 1990 to 2021, revealing notable variations across SDI regions, countries, age groups, and sexes. Besides, deaths and DALYs are predicted to rise by 2050. These results highlight the importance of implementing measures to address the growing burden of EO-CRC globally.

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

Early onset Colorectal Cancer (EOCRC), defined as those diagnosed under the age of 50, has been increasing rapidly since 1970. UK data on EOCRC are currently limited and better understanding of the condition is needed.

A single-center retrospective study of patients with EOCRC treated over 9 years (2013-2021) at a large UK cancer center was performed. Clinicopathological features, risk factors, molecular drivers, treatment, and survival were analyzed.

In total, 203 patients were included. A significant increase in cases was reported from 2018-2019 (n = 33) to 2020-2021 (n = 118). Sporadic EOCRC accounted for 70% of cases and left-sided tumors represented 70.9% (n = 144). Median duration of symptoms was 3 months, while 52.7% of the patients had de-novo metastatic disease. Progression-free survival after first-line chemotherapy was 6 months (95% CI, 4.85-7.15) and median overall survival (OS) was 38 months (95% CI, 32.86-43.14). In the advanced setting, left-sided primary tumors were associated with a median OS benefit of 14 months over right-sided primaries (28 vs 14 months, P = .009). Finally, primary tumor resection was associated with median OS benefit of 21 months compared with in situ tumors (38 vs 17 months, P < .001).

The incidence of EOCRC is increasing, and survival outcomes remain modest. Raising public awareness and lowering the age for colorectal cancer screening are directions that could improve EOCRC clinical outcomes. There is also a need for large prospective studies to improve the understanding of the nature of EOCRC and the best therapeutic approaches.

Epidemiologic evidence for dietary influence on colorectal cancer (CRC) risk through the gut microbiome remains limited.

Leveraging 307 men and 212 women with stool metagenomes and dietary data, we characterized and validated a sex-specific dietary pattern associated with the CRC-related gut microbial signature (CRC Microbial Dietary Score [CMDS]). We evaluated the associations of CMDS with CRC risk according to Fusobacterium nucleatum, pks+Escherichia coli, and enterotoxigenic Bacteroides fragilis status in tumor tissue using Cox proportional hazards regression in the Health Professionals Follow-Up Study (1986-2018), Nurses' Health Study (1984-2020), and Nurses' Health Study II (1991-2019).

The CMDS was characterized by high industrially processed food and low unprocessed fiber-rich food intakes. In 259,200 participants, we documented 3854 incident CRC cases over 6,467,378 person-years of follow-up. CMDS was associated with a higher risk of CRC (Ptrend < .001), with a multivariable hazard ratio (HRQ5 vs Q1) of 1.25 (95% CI, 1.13-1.39). The association remained after adjusting for previously established dietary patterns, for example, the Western and prudent diets. Notably, the association was stronger for tumoral F nucleatum-positive (HRQ5 vs Q1, 2.51; 95% CI, 1.68-3.75; Ptrend < .001; Pheterogeneity = .03, positivity vs negativity), pks+E coli-positive (HRQ5 vs Q1, 1.68; 95% CI, 0.84-3.38; Ptrend = .005; Pheterogeneity = .01, positivity vs negativity), and enterotoxigenic Bacteroides fragilis-positive CRC (HRQ5 vs Q1, 2.06; 95% CI, 1.10-3.88; Ptrend = .016; Pheterogeneity = .06, positivity vs negativity), compared with their negative counterparts.

CMDS was associated with increased CRC risk, especially for tumors with detectable F nucleatum, pks+E coli, and enterotoxigenic Bacteroides fragilis in tissue. Our findings support a potential role of the gut microbiome underlying the dietary effects on CRC.

This systematic review aims to investigate the microbial basis underlying the association between oral microbiota and colorectal cancer. A comprehensive search was conducted across four databases, encompassing potentially relevant studies published up to April 2024 related to the PECO question: "Is there a differentiation in oral microbial composition between adult patients diagnosed with colorectal cancer compared to healthy patients?". The Newcastle-Ottawa Scale was used to evaluate the quality of the studies included. The level of evidence was assessed through the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) tool. Sixteen studies fulfilled the eligibility criteria. Based on low to moderate evidence profile, high levels of certain subspecies within Firmicutes (such as Streptococcus anginosus, Peptostreptococcus stomatis, S. koreensis, and S. gallolyticus), Prevotella intermedia, Fusobacterium nucleatum, and Neisseria oralis were found to be associated with colorectal cancer. Conversely, certain bacteria (e.g., Lachnospiraceae, F. periodonticum, and P. melaninogenica) could exert a symbiotic protective effect against colorectal cancer. Based on existing evidence, it appears that variations in oral microbiota composition exist among individuals with and without colorectal cancer. However, further research is necessary to determine the mechanisms of oral dysbiosis in colorectal carcinogenesis.

Sex differences in colorectal cancer (CRC) has received considerable research attention recently, particularly regarding the influence of sex hormones and the intestinal microbiota. Estrogen, at the genetic and epigenetic levels, directly inhibits CRC cell proliferation by enhancing DNA mismatch repair, regulating miRNAs, blocking the cell cycle, and modulating ion channels. However, estradiol's activation of GPER promotes oncogene expression. Conversely, androgen contributes to epigenetic dysregulation and CRC progression via nuclear receptors while inducing apoptosis through membrane receptors. Specific gut microorganisms produce genotoxins and oncogenic metabolites that damage colonic cell DNA and contribute to cancer induction. Regarding the tumor microenvironment, estrogen mitigates intestinal inflammation, reverses immunosuppression, increases gut microbiome diversity and commensal bacteria abundance, and decreases pathogen enrichment. On the contrary, androgen disrupts intestinal microecology, diminish immunotherapy efficacy, and exacerbate colonic inflammation and tumor growth. The impact of estrogen and androgen is closely tied to their receptor status, elucidating their dual roles in CRC pathogenesis. This review comprehensively discusses the direct and indirect effects of sex hormones and the intestinal microbiota on CRC, considering environmental factors such as diet and lifestyle to propose novel prevention and treatment strategies.

The Non-Healthy Diet Index (NHDI) and the Pro-Healthy Diet Index (PHDI) are two novel indices that evaluate the healthiness of a diet based on the consumption of several food groups. This study aimed to evaluate the association between adherence to the PHDI and NHDI and colorectal cancer (CRC) risk in the Iranian population.

The current study was conducted as a hospital-based research using a case (n = 71)- matched-controls (n = 142) design in Tehran, Iran. A semi-quantitative food frequency questionnaire was utilized to determine participants' dietary intake after confirming the diagnosis of CRC and at the time of the interview. The PHDI-10 was employed to assess the consumption of foods with positive health effects, which is linked to the frequency of consuming 10 food groups, and the NHDI-14 was used to assess the consumption of foods that have detrimental effects on health, based on the frequency of 14 food groups. Logistic regression was used to evaluate the association between continuous PHDI and NHDI scores and their tertiles with CRC.

The results indicated that individuals in the highest tertile of the PHDI showed a lower CRC risk compared to those in the lowest tertile (adjusted model- odds ratio (OR) = 0.25; 95% confidence interval (CI): 0.10-0.61; P = 0.002). Also, lower odds of CRC risk were seen with each unit change in the total score of PHDI in the adjusted model (OR = 0.86; 95% CI: 0.76-0.96; P = 0.009). In contrast, individuals in the highest tertile of the NHDI showed a higher risk of CRC compared to those in the lowest tertile (OR = 2.62; 95% CI: 1.09-6.27; P = 0.030) in the adjusted model. Also, higher odds of CRC risk were observed with each unit increase in the total score of NHDI in the adjusted model (OR = 1.13; 95% CI: 1.03-1.25; P = 0.008).

The present study showed that higher adherence to PHDI and NHDI is associated with lower and higher CRC risk, respectively. These results provide valuable insights into the roles of healthy and unhealthy diets in CRC prevention.

Appropriate host-microbiota interactions are essential for maintaining intestinal homeostasis; hence, an imbalance in these interactions leads to inflammation-associated intestinal diseases. Toll-like receptors (TLRs) recognize microbial ligands and play a key role in host-microbe interactions in health and disease. TLR13 has a well-established function in enhancing host defenses against pathogenic bacteria. However, its role in maintaining intestinal homeostasis and controlling colitis-associated colon cancer (CAC) is largely unknown. This study aimed to investigate the involvement of TLR13-mediated signaling in intestinal homeostasis and colonic tumorigenesis using ex vivo cell and in vivo CAC animal model. Tlr13-deficient mice were prone to dextran sodium sulfate (DSS)-induced colitis. During the early stages of the CAC regimen (AOM/DSS-treated), Tlr13 deficiency led to severe ulcerative colitis. Moreover, Tlr13-deficient mice exhibited increased intestinal permeability, as evidenced by elevated levels of fluorescein isothiocyanate (FITC)-dextran, endotoxins, and bacterial translocation. Enhanced cell survival and proliferation of colonic intestinal cells were observed in Tlr13-deficient mice. A transcriptome analysis revealed that Tlr13 deficiency is associated with substantial changes in gene expression profile of colonic tumor tissue. Tlr13-deficient mice were more susceptible to CAC, with increased production of interleukin (IL)-6, IL-12, and TNF-α cytokines and enhanced STAT3, NF-κB, and MAPK signaling in colon tissues. These findings suggest that TLR13 plays a protective role in maintaining intestinal homeostasis and controlling CAC. Our study provides a novel perspective on intestinal health via TLR13-mediated signaling, which is crucial for deciphering the role of host-microbiota interactions in health and disease.

The growing incidence and high mortality rate of breast cancer (BC) in Nigeria is attributed to increased risk levels, poor prognosis and late detection.

This study aimed at identifying education-based disparities in BC risk knowledge, lifestyle/ dietary patterns among females in Ogun state, Nigeria. Questionnaires were used to obtain data from 1135 study participants across various levels of education and analyzed using Epi-info software and Graphpad prism.

The lifestyle/dietary pattern assessment revealed that the participants in the secondary level smoked the most (4.50%), accompanied by high red wine (31.00%), fruits and vegetable (73.00%) consumption. Graduates had the highest antibiotics intake (54.50%) and alcohol consumption (12.00%), the undergraduates were the most physically inactive (63.90%) with the highest consumption of carbonated drinks (73.90%), postgraduates consumed red meat/smoked foods the most (70.70%).

The knowledge of BC risk positively impacted carbonated drinks, physical inactivity, smoking, antibiotics and alcohol intake. However, it did not affect family history, red meat/smoked foods, fruits and vegetables consumption. Overall, Education has an impact on the knowledge of BC risks which influences the lifestyle/dietary patterns of females in Nigeria.

A correlation between omega-3 polyunsaturated fatty acids (omega-3 PUFAs) and osteoarthritis (OA) incidence has been established, but research on the long-term outlook of OA patients remains limited. This study investigates the association between omega-3 PUFA intake and the risk of all-cause and cardiovascular (CV) mortality in the U.S. OA population. A cohort of 3,467 OA patients from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 was studied. Cox proportional hazards regression models, Kaplan-Meier curves, and subgroup analyses were used to evaluate the relationship between omega-3 PUFA intake and mortality. The dose-response relationship was examined using a restricted cubic spline (RCS) model. Among the 3,467 OA patients, there were 459 all-cause deaths and 175 CV deaths. Omega-3 PUFAs were significantly negatively correlated with all-cause mortality (95% CI: 0.59-0.93, p = 0.011) but not with CV mortality (95% CI: 0.29-1.04, p = 0.056). Higher omega-3 PUFA intake was associated with a 49% decrease in all-cause mortality. Kaplan-Meier curves showed lower all-cause mortality rates in those with higher omega-3 PUFA intake. The inverse correlation was more pronounced among individuals living with a partner. The dose-response analysis indicated a linear negative relationship between omega-3 PUFA intake and all-cause mortality. Increased intake of omega-3 PUFAs is associated with a decreased risk of all-cause mortality in OA patients.

The intestinal microbiome plays a crucial role in colorectal adenomas and the mucosa associated microbiota are thought to play a more critical role in interactions with the host immune system. Current omics approaches, offer a holistic assessment of the gut microbiome and the human host interaction. To enhance the value of data from these sequencing methods, appropriate sample collection is vital. We evaluated the potential use of endoscopic brush samples for mucosal microbiota analysis in colorectal adenomas and compared it with direct adenoma tissue sequencing in terms of microbial gene sequencing. The results showed a significant increase in microbial diversity in samples collected by the endoscopic brush, which did not interfere with pathological biopsy. This study found that utilizing endoscopic brush sampling for the microbiome analysis of colorectal adenomas offers several advantages over the direct examination of microbiomes within tumor tissues, including the capacity to accurately collect gut microbiome from different locations in the intestine, circumventing interference from tissue genes, providing more abundant microbial data and enabling inclusion of small adenomas without disrupting pathological biopsies.

Individuals with Familial Adenomatous Polyposis (FAP) or APC-associated polyposis, an autosomal dominant inherited condition, develop multiple adenomatous polyps and have an increased colorectal cancer (CRC) risk. A change in diet can help reduce cancer risk, and several dietary components have an antitumor effect. We aimed to evaluate the potential of the anti-inflammatory and anticancer substances quercetin (QER), epigallocatechin gallate (EGG) and fisetin (FIS) in decreasing the risk of CRC by reducing the growth of polyps in an organoid model.

Patient-derived organoid (PDO) lines were generated from polyps obtained from patients with FAP undergoing prophylactic colectomy. PDOs were treated with QER, EGG, or FIS to determine their effect on cell growth. Changes in caspase 3/7 activity and expression of inflammation and apoptosis mediators were assessed by luminescent and colorimetric assays.

Three PDO lines with different inactivating pathogenic variants in the APC gene were developed using a combinatorial approach. FIS was the most active of the three substances tested, presenting the lowest IC50 in all PDO lines (range: 42.6-9.2 uM). The IC50 was defined as the concentration required to halve the number of cells after 72 hours. All molecules tested induced apoptosis through activation of caspases 3/7.

QER, EGG, and FIS can be easily taken from foods or dietary supplements, show toxicity on PDOs derived from adenomatous polyps, while they are known to be harmless on normal cells. Diets enriched with these substances could be potential supplemental treatments to reduce the risk of CRC in individuals with FAP.

The early-life gut microbiota (GM) is increasingly recognized for its contributions to human health and disease over time. Microbiota composition, influenced by factors like race, geography, lifestyle, and individual differences, is subject to change. The GM serves dual roles, defending against pathogens and shaping the host immune system. Disruptions in microbial composition can lead to immune dysregulation, impacting defense mechanisms. Additionally, GM aids digestion, releasing nutrients and influencing physiological systems like the liver, brain, and endocrine system through microbial metabolites. Dysbiosis disrupts intestinal homeostasis, contributing to age-related diseases. Recent studies are elucidating the bacterial species that characterize a healthy microbiota, defining what constitutes a 'healthy' colonic microbiota. The present review article focuses on the importance of microbiome composition for the development of homeostasis and the roles of GM during aging and the age-related diseases caused by the alteration in gut microbial communities. This article might also help the readers to find treatments targeting GM for the prevention of various diseases linked to it effectively.