Occurrence Of Colorectal Cancer Research Articles

Gut microbiota characteristics of colorectal cancer patients in Hubei, China, and differences with cohorts from other Chinese regions.

The research on the correlation or causality between gut microbiota and the occurrence, development, and treatment of colorectal cancer (CRC) is receiving increasing emphasis. At the same time, the incidence and mortality of colorectal cancer vary among individuals and regions, as does the gut microbiota. In order to gain a better understanding of the characteristics of the gut microbiota in CRC patients and the differences between different regions, we initially compared the gut microbiota of 25 CRC patients and 26 healthy controls in the central region of China (Hubei Province) using 16S rRNA high-throughput sequencing technology. The results showed that Corynebacterium, Enterococcus, Lactobacillus, and Escherichia-Shigella were significantly enriched in CRC patients. In addition, we also compared the potential differences in functional pathways between the CRC group and the healthy control group using PICRUSt's functional prediction analysis. We then analyzed and compared it with five cohort studies from various regions of China, including Central, East, and Northeast China. We found that geographical factors may affect the composition of intestinal microbiota in CRC patients. The composition of intestinal microbiota is crucial information that influences colorectal cancer screening, early detection, and the prediction of CRC treatment outcomes. This emphasizes the importance of conducting research on CRC-related gut microbiota in various regions of China.

Berberine: Potential preventive and therapeutic strategies for human colorectal cancer.

Colorectal cancer (CRC) is a common digestive tract tumor, with incidences continuing to rise. Although modern medicine has extended the survival time of CRC patients, its adverse effects and the financial burden cannot be ignored. CRC is a multi-step process and can be caused by the disturbance of gut microbiome and chronic inflammation's stimulation. Additionally, the presence of precancerous lesions is also a risk factor for CRC. Consequently, scientists are increasingly interested in identifying multi-target, safe, and economical herbal medicine and natural products. This paper summarizes berberine's (BBR) regulatory mechanisms in the occurrence and development of CRC. The findings indicate that BBR regulates gut microbiome homeostasis and controls mucosal inflammation to prevent CRC. In the CRC stage, BBR inhibits cell proliferation, invasion, and metastasis, blocks the cell cycle, induces cell apoptosis, regulates cell metabolism, inhibits angiogenesis, and enhances chemosensitivity. BBR plays a role in the overall management of CRC. Therefore, using BBR as an adjunct to CRC prevention and treatment could become a future trend in oncology.

Research on the Effect and Mechanism of Selenium on Colorectal Cancer Through TRIM32.

The intake of selenium (Se) in the human body is negatively correlated with the risk of colorectal cancer (CRC), but its mechanism in the occurrence and development of CRC is not clear. This study aimed to evaluate the therapeutic effect of Se on CRC, and explore the anti-tumor effect of Se supplementation on CRC and its molecular mechanism. In this study, we utilized colony formation assay, cell scratch test, Transwell migration, and flow cytometry to assess cell proliferation, migration, and apoptosis. Our findings demonstrate that Se effectively suppresses the growth and proliferation of CRC cell lines HCT116 and SW480 and promoting cellular apoptosis. In vivo experiments demonstrated a significant inhibitory effect of Se on tumor growth. CRC-related datasets were extracted from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases for differential expression analysis of TRIM32 and survival analysis. We found that TRIM32 was highly expressed in tumor tissues of CRC patients and correlated with a poor prognosis. Furthermore, through RNA sequencing analysis, we identified TRIM32 as a gene that was significantly decreased after Se treatment in HCT116 cells. This finding was subsequently validated by Western blot results. Moreover, TRIM32 knockdown combined with Se treatment significantly inhibited cell growth proliferation and migration and further induced apoptosis of colorectal cancer cells. In conclusion, our findings provided evidence that Se inhibited the growth of colorectal cancer cells by down-regulating TRIM32.

Clinical, epidemiological and genetic features of colorectal cancer

Introduction. The incidence of colorectal cancer for 2020 was 1931590 cases, which is 10 % of all new cases of incidence, and mortality from colorectal cancer ranks 2nd among cancer deaths, it is 935 173 cases (9.4 %) according to Globocan 2020. According to statistics of the Kazakh Research Institute of Oncology and Radiology for 2019–2020 сolorectal cancer ranks 3rd in the structure of oncopathology, both in terms of morbidity and mortality. The occurrence of colorectal cancer is associated with an interaction that occurs at several levels between hereditary, environmental and individual factors. Understanding the molecular basis is important because it can identify factors that initiate development, maintain progression, and determine response or resistance to anticancer agents.Aim. To describe the main genetic mutations and their impact on treatment prognosis, diagnosis and course of colorectal cancer.Materials and methods. A systematic literature review of scientific databases Cochrane, PubMEd, MedLine, Elsevier was carried out. For the main search, the main search terms are formulated: colorectal cancer, mutations in colorectal cancer, molecular genetic studies in colorectal cancer, mutation of the KRAS gene. Also, a time range was set no later than 5 years, i. e. all articles published from 2017 to the current year.Results. The main molecular changes in colorectal cancer are Chromosome instability, microsatellite instability, and abnormal DNA methylation. Suppressor genes, such as Ras, EGFR (Erb-B1), Erb-B2, TGF-alpha, and TGF-beta 1, are also of great importance.Conclusion. Research that contributes to the understanding of the molecular basis of colorectal cancer helps in the early diagnosis of familial cancer, treatment prognosis and a personalized approach to patient treatment.

Oxidative balance score: a potential tool for reducing the risk of colorectal cancer and its subsites incidences.

The Oxidative Balance Score (OBS) is commonly used to assess oxidative stress and provides a comprehensive evaluation of dietary and lifestyle-related exposures. However, there is limited research on the association between OBS and colorectal cancer (CRC), its subsites, and complications. The objective of this study was to assess the relationship between OBS and the risk of CRC, its subsites, and common complications in a large prospective cohort study. We included data from 175,808 participants in the UK Biobank data sample repository from 2006 to 2010. We evaluated OBS using a scoring system based on 22 dietary and lifestyle factors. Multiple adjustments, including multivariate Cox proportional hazard regression, gender stratification, subgroup analysis, and sensitivity analysis, were performed to fully explore the relationship between OBS and CRC, its subsites, and complications. The mediation analysis was conducted to investigate whether serum albumin, uric acid, and neutrophil levels mediate the relationship between OBS and CRC. After adjusting for potential confounding factors, a significant negative correlation was found between OBS and the risk of CRC and its subsites (proximal colon cancer, distal colon cancer, and rectal cancer). This correlation was particularly pronounced in male CRC patients. Serum albumin, uric acid, and neutrophil count, which are biomarkers, were found to have a significant mediating effect between OBS and CRC. Our study suggests that higher exposure to antioxidants assessed through OBS (diet and lifestyle rich in antioxidants) may decrease the occurrence of CRC and its subsites.

Mineral crude drug mirabilite (Mangxiao) inhibits the occurrence of colorectal cancer by regulating the Lactobacillus-bile acid-intestinal farnesoid X receptor axis based on multiomics integration analysis.

Mineral crude drug has revolutionized the treatment landscape in precision oncology niche that leads to the improvement in therapeutic efficiency on various tumor subtypes. Mangxiao (MX), a mineral crude drug in traditional Chinese medicine, has been used for treating gastrointestinal diseases for thousands of years. However, the action mechanisms are still ambiguous. Here, we attempt to explore inhibitory roles and associated pharmacological mechanisms of MX upon colorectal cancer (CRC) in APCMin/+ male mice by integrating metabolomics, 16S rDNA sequencing analyses, and metagenomic-based microbiota analysis. We found that MX can significantly inhibit the occurrence of CRC through the regulation of the dysregulated gut microbe metabolism. Furthermore, the correlation analysis of metabolomes and 16S rDNA revealed that MX could restore the disorders of gut microbes by specifically enriching the abundance of Lactobacilli to improve bile acid metabolism, which further activated the farnesoid X receptor (FXR) in CRC mice, then the improvement of gut dysbiosis could inhibit the development of CRC. Collectively, our effort confirmed MX has the capacity to intervene the development of CRC and further discovered that it targets Lactobacillus-bile acid-intestinal FXR axis, which can be regarded as a candidate medicine for future drug discovery and development against CRC.

Fusobacterium nucleatum-induced imbalance in microbiome-derived butyric acid levels promotes the occurrence and development of colorectal cancer.

Colorectal cancer (CRC) ranks among the most prevalent malignant tumors globally. Recent reports suggest that Fusobacterium nucleatum (F. nucleatum) contributes to the initiation, progression, and prognosis of CRC. Butyrate, a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber, is known to inhibit various cancers. This study is designed to explore whether F. nucleatum influences the onset and progression of CRC by impacting the intestinal metabolite butyric acid. To investigate the mechanism by which F. nucleatum affects CRC occurrence and development. Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of F. nucleatum. Additionally, DLD-1 and HCT116 cell lines were exposed to sodium butyrate (NaB) and F. nucleatum in vitro to examine the effects on proliferative proteins and mitochondrial function. Our research indicates that the prevalence of F. nucleatum in fecal samples from CRC patients is significantly greater than in healthy counterparts, while the prevalence of butyrate-producing bacteria is notably lower. In mice colonized with F. nucleatum, the population of butyrate-producing bacteria decreased, resulting in altered levels of butyric acid, a key intestinal metabolite of butyrate. Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells. Consequently, this leads to modulated production of adenosine triphosphate and reactive oxygen species, thereby inhibiting cancer cell proliferation. Additionally, NaB triggers the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, blocks the cell cycle in HCT116 and DLD-1 cells, and curtails the proliferation of CRC cells. The combined presence of F. nucleatum and NaB attenuated the effects of the latter. By employing small interfering RNA to suppress AMPK, it was demonstrated that AMPK is essential for NaB's inhibition of CRC cell proliferation. F. nucleatum can promote cancer progression through its inhibitory effect on butyric acid, via the AMPK signaling pathway.

The Influence of Sex and/or Gender on the Occurrence of Colorectal Cancer in the General Population in Developed Countries: A Scoping Review.

Objective: Gender as the "sociocultural role of sex" is underrepresented in colorectal cancer incidence studies, potentially resulting in underestimated risk factors' consequences and inequalities men/women. We aim to explore how literature focusing on differences between men and women in the incidence of colorectal cancer interprets these differences: through sex- or gender-related mechanisms, or both? Methods: We conducted a scoping review using PubMed and Google Scholar. We categorized studies based on their definitions of sex and/or gender variables. Results: We reviewed 99 studies, with 7 articles included in the analysis. All observed differences between men and women. Six articles examined colorectal cancer incidence by gender, but only 2 used the term "gender" to define exposure. One article defined its "sex" exposure variable as gender-related mechanisms, and two articles used "sex" and "gender" interchangeably to explain these inequalities. Gender mechanisms frequently manifest through health behaviors. Conclusion: Our results underscore the need for an explicit conceptual framework to disentangle sex and/or gender mechanisms in colorectal cancer incidence. Such understanding would contribute to the reduction and prevention of social health inequalities.

Retraction Note: Long non-coding RNA DLEU7-AS1 promotes the occurrence and development of colorectal cancer via Wnt/β-catenin pathway.

The article "Long non-coding RNA DLEU7-AS1 promotes the occurrence and development of colorectal cancer via Wnt/β-catenin pathway", by X.-B. Liu, C. Han, C.-Z. Sun, published in Eur Rev Med Pharmacol Sci 2018; 22 (1): 110-117-DOI: 10.26355/eurrev_201801_14107-PMID: 29364477 has been retracted by the authors as the data cannot be reproduced by further research. This paper has been questioned on PubPeer (https://pubpeer.com/publications/AC72791669051B50085FEC00D0EF8F). In particular, concerns were raised about Table I and the originality of Figures 3A and 3C. The corresponding author states some data cannot be repeated by further research due to some inaccuracies and therefore decided to withdraw the manuscript. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14107.

Cancer-specific risk prediction with a serum microRNA signature.

We recently derived and validated a serum-based microRNA risk score (miR-score) that predicted colorectal cancer (CRC) occurrence with very high accuracy within 14 years of follow-up in a population-based cohort study from Germany (ESTHER cohort). Here, we aimed to evaluate associations of the CRC-specific miR-score with the risk of developing other common cancers, including female breast cancer (BC), lung cancer (LC), and prostate cancer (PC), in the ESTHER cohort. MicroRNAs (miRNAs) were profiled by quantitative real-time PCR in serum samples collected at baseline from randomly selected incident cases of BC (n = 90), LC (n = 88), and PC (n = 93) and participants without diagnosis of CRC, LC, BC, or PC (controls, n = 181) until the end of the 17-year follow-up. Multivariate logistic regression models were used to evaluate the associations of the miR-score with BC, LC, and PC incidence. The miR-score showed strong inverse associations with BC and LC incidence [odds ratio per 1 standard deviation increase: 0.60 (95% confidence interval [CI] 0.43-0.82), p = 0.0017, and 0.64 (95% CI 0.48-0.84),p = 0.0015, respectively]. Associations with PC were not statistically significant but pointed in the positive direction. Our study highlights the potential of serum-based miRNA biomarkers for cancer-specific risk prediction. Further large cohort studies aiming to investigate, validate, and optimize the use of circulating miRNA signatures for cancer risk assessment are warranted.

Bifidobacterium longum suppresses colorectal cancer through the modulation of intestinal microbes and immune function.

Colorectal cancer (CRC), one of the most common malignancies in the world, urgently requires more treatment strategies. Although there has been much research on probiotics, limited research has been done in treating cancer. The purpose of this study was to investigate the role of Bifidobacterium longum (B. longum) in the prevention and treatment of CRC. Through Cell Counting Kit-8 and Colony Formation Assays, 8 h and a B. longum count of 1 × 108 CFU/ml were chosen as the best cocultivation conditions with CRC cells. The role of B. longum in inhibiting the progression of CRC cells was verified by a series of functional and immunofluorescence assays. For instance, in vivo assays have verified that B. longum could alleviate CRC progression. In addition, according to the results of in vivo assays and clinical statistical analysis, B. longum could reduce diarrhea symptoms. Mechanistically, by 16S and RNA sequencing, it was found that B. longum could affect the development of CRC by regulating the composition of gut microbes and enhancing immune function. The B. longum might inhibit the occurrence and development of CRC and relieve diarrhea symptoms by regulating intestinal microbes and immune function.

Association between the gut microbiota, inflammatory factors, and colorectal cancer: evidence from Mendelian randomization analysis.

Colorectal cancer (CRC) is one of the most common malignant tumors primarily affecting individuals over the age of 50 years. Recent studies have suggested that the dysbiosis of the gut microbiota, a community of microorganisms in the human gut, is closely associated with the occurrence and development of CRC. Additionally, inflammatory factors (IFs) have also been reported to play a significant role in the development of CRC. However, the causal relationships between the gut microbiota, IFs, and CRC remain unclear. In this study, we performed Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) data to explore the causal relationship between the gut microbiota, IFs, and CRC. The gut microbiota GWAS data were obtained from the MiBioGen study, while the IFs GWAS data were derived from the comprehensive analysis of three independent cohorts. Causal relationship analysis was conducted using appropriate instrumental variables (IVs) and statistical models. MR analysis of the gut microbiota and CRC revealed a negative correlation between the Lachnospiraceae species in the gut and CRC risk, while a positive correlation was observed between Porphyromonadaceae species, Lachnospiraceae UCG010 genus, Lachnospira genus, and Sellimonas genus in the gut, and CRC risk. Additionally, we observed a causal relationship between IL-10 and CRC risk. These findings suggest that the dysbiosis of the gut microbiota might be associated with an increased risk of CRC and that specific bacterial groups may play a crucial role in the occurrence and development of CRC. Using MR analysis, this study revealed the causal relationships between the gut microbiota, IFs, and CRC. The negative correlation between the Lachnospiraceae species in the gut and CRC risk, as well as the causal relationship between IL-10 and CRC, provide important clues for the potential roles of gut microbiota regulation and inflammatory factor control in the prevention and treatment of CRC.

Epigenetic Alteration in Colorectal Cancer: Potential Diagnostic and Prognostic Implications.

Colorectal cancer (CRC), a prevalent malignant tumor of the digestive system, ranks as the third and second in global incidence and mortality, respectively, in 2020, with 1.93 million new cases (≈10% of all cancers). There are 940,000 deaths (≈9.4% of all cancers), and the incidence of CRC in younger patients (under 50 years of age) has become a new trend. The pathogenesis of CRC is primarily attributed to a series of genetic and epigenetic abnormalities within normal colonic epithelial cells, coupled with the reshaping of the tumor microenvironment in the surrounding stroma. This process leads to the transformation of colorectal adenomas into invasive adenocarcinomas. Although genetic changes are known to be the primary driving force in the occurrence and progression of CRC, recent research indicates that epigenetic regulation serves as a crucial molecular marker in cancer, playing a significant role in the pathological and physiological control of interactions between genetics and the environment. This review discusses the current global epidemiology of CRC, its risk factors, and preventive treatment strategies. The current study explores the latest advancements in the epigenetic regulation of CRC, including DNA methylation, histone modifications, and non-coding RNAs (ncRNAs). These developments hold potential as screening tools, prognostic biomarkers, and therapeutic targets for CRC.

Deciphering alternative splicing events and their therapeutic implications in colorectal Cancer

Colorectal cancer (CRC) is one of the most common malignant tumors with complex molecular regulatory mechanisms. Alternative splicing (AS), a fundamental regulatory process of gene expression, plays an important role in the occurrence and development of CRC. This study analyzed AS Percent Spliced In (PSI) values from 49 pairs of CRC and normal samples in the TCGA SpliceSeq database. Using Lasso and SVM, AS features that can differentiate colorectal cancer from normal were screened. Univariate COX regression analysis identified prognosis-related AS events. A risk model was constructed and validated using machine learning, Kaplan-Meier analysis, and Decision Curve Analysis. The regulatory effect of protein arginine methyltransferase 5 (PRMT5) on poly(RC) binding protein 1 (PCBP1) was verified by immunoprecipitation experiments, and the effect of PCBP1 on the AS of Obscurin (OBSCN) was verified by PCR. Five AS events, including HNF4A.59461.AP and HNF4A.59462.AP, were identified, which can distinguish CRC from normal tissue. A machine learning model using 21 key AS events accurately predicted CRC prognosis. High-risk patients had significantly shorter survival times. PRMT5 was found to regulate PCBP1 function and then influence OBSCN AS, which may drive CRC progression. The study concluded that some AS events is significantly different in CRC and normal tissues, and some of these AS events are related to the prognosis of CRC. In addition, PRMT family-driven arginine modifications play an important role in CRC-specific AS events.

Exploring the nexus between obesity, metabolic syndrome, and colorectal cancer

The increasing global prevalence of obesity and metabolic syndrome (MetS) is strongly associated with the incidence of colorectal cancer (CRC). Obesity and MetS detrimentally impact the treatment outcomes of CRC and share similar mechanisms that contribute to the development of CRC. Increased insulin resistance in patients with obesity is linked to CRC, and altered levels of sex hormones and adipokines affect cell growth and inflammation. Obesity and MetS also alter the gut microbiome. Bile acids, which are crucial for lipid metabolism, are elevated in patients with obesity. Moreover, specific bile acids are associated with colonic damage, inflammation, and the development of CRC. Obesity and MetS increase the risk of postoperative complications and affect the response to chemotherapy. The promotion of weight loss and the resolution of MetS can reduce the occurrence of CRC and increase treatment efficacy. Therefore, it is imperative to implement appropriate management strategies to address obesity and MetS with the aim of improving the prognosis and reducing the incidence of CRC. Moreover, additional research should be conducted to determine the optimal timing for tailored CRC screening in patients with obesity or MetS. In this review, we explore the impact of obesity and MetS on the development of CRC and examine potential strategies to mitigate CRC risk in individuals with obesity and MetS.

The association of metabolic syndrome score trajectory patterns with risk of all cancer types.

Metabolic syndrome (MetS) elevates cancer risk. However, a single MetS assessment does not fully reveal the long-term association with cancer. Inflammation, alongside MetS, could synergistically expedite both the onset and advancement of cancer. This study aims to investigate MetS score trajectories and cancer risk in a large, prospective cohort study. The authors prospectively examined the relationship between MetS score trajectory patterns and new-onset cancer in 44,115 participants. Latent mixture modeling was used to identify the MetS score trajectories. Cox proportional hazards regression models were used to evaluate the association between MetS score trajectory patterns and the risk of overall and site-specific cancers. Four MetS score trajectory patterns were identified: low-stable (n=4657), moderate-low (n=18,018), moderate-high (n=18,288), and elevated-increasing (n=3152). Compared to participants with a low-stable trajectory pattern, the elevated-increasing trajectory pattern was associated with an elevated risk of overall (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.04-1.55), breast (HR, 2.11; 95% CI, 1.04-4.34), endometrial (HR, 3.33; 95% CI, 1.16-6.77), kidney (HR, 4.52; 95% CI, 1.17-10.48), colorectal (HR, 2.54; 95% CI, 1.27-5.09), and liver (HR,1.61; 95% CI, 1.09-4.57) cancers. Among participants with chronic inflammation (C-reactive protein levels ≥3mg/L), the elevated-increasing trajectory pattern was significantly associated with subsequent breast, endometrial, colorectal, and liver cancers. Trajectories of MetS scores are associated with the occurrence of cancers, especially breast, endometrial, kidney, colorectal, and liver cancers, emphasizing the importance of long-term monitoring and evaluation of MetS. The association between long-term elevated metabolic syndrome (MetS) scores and a heightened risk of various cancers is a pivotal finding of our study. Our research further indicates that individuals with MetS, particularly when coupled with chronic inflammation, are at an increased risk of cancer. We propose that sustained monitoring and management of MetS could be beneficial in reducing cancer risk.

The CK1ε/SIAH1 axis regulates AXIN1 stability in colorectal cancer cells.

Casein kinase 1ε (CK1ε) and axis inhibitor 1 (AXIN1) are crucial components of the β-catenin destruction complex in canonical Wnt signaling. CK1ε has been shown to interact with AXIN1, but its physiological function and role in tumorigenesis remain unknown. In this study, we found that CK1δ/ε inhibitors significantly enhanced AXIN1 protein level in colorectal cancer (CRC) cells through targeting CK1ε. Mechanistically, CK1ε promoted AXIN1 degradation by the ubiquitin-proteasome pathway by promoting the interaction of E3 ubiquitin-protein ligase SIAH1 with AXIN1. Genetic or pharmacological inhibition of CK1ε and knockdown of SIAH1 downregulated the expression of Wnt/β-catenin-dependent genes, suppressed the viability of CRC cells, and restrained tumorigenesis and progression of CRC in vitro and in vivo. In summary, our results demonstrate that CK1ε exerted its oncogenic role in CRC occurrence and progression by regulating the stability of AXIN1. These findings reveal a novel mechanism by which CK1ε regulates the Wnt/β-catenin signaling pathway and highlight the therapeutic potential of targeting the CK1ε/SIAH1 axis in CRC.

Gut microbiota and epigenetics in colorectal cancer: implications for carcinogenesis and therapeutic intervention.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. The occurrence of CRC is associated with various genetic and epigenetic mutations in intestinal epithelial cells that transform them into adenocarcinomas. There is increasing evidenceindicating thegut microbiota playsa crucial role in the regulation of host physiological processes. Alterations in gut microbiota composition are responsible for initiating carcinogenesis through diverse epigenetic modifications, including histone modifications, ncRNAs and DNA methylation. This work was designedto comprehensively reviewrecent findings to provide insight into the associations between the gut microbiota and CRC at an epigenetic level. These scientific insights can be used in the future to develop effective strategies for early detection and treatment of CRC.

Clinical efficacy of metformin in familial adenomatous polyposis and the effect of intestinal flora.

Metformin has been reported to inhibit the occurrence and development of colorectal cancer (CRC) by mediating changes in intestinal flora. Studies have also indicated that the occurence of familial adenomatous polyposis (FAP) may also be associated with changes in the intestinal flora. Therefore, we investigated the efficacy and safety of metformin in treating FAP and the association with intestinal flora. Compared with the baseline, the mean number and load of polyps in the areas of nanocarbon labeling and postoperative residuals in the test group were lower than those in the placebo group, while the diversity of intestinal flora species was increased. At the genus level, the relative abundance of g_Ruminococcus in the test group was lower than that at baseline, whereas the relative abundance of g_Lactobacillus was higher. These changes were statistically significant (P < 0.05). One-year metformin therapy for FAP is safe and effective, potentially mediated by modulating the intestinal flora. This study provides new insights and strategies for preventing adenomatous polyp carcinogenesis in FAP and explores possible preventive action.

Banxia Xiexin Decoction delays colitis-to-cancer transition by inhibiting E-cadherin/β-catenin pathway via Fusobacterium nucleatum FadA

Ethnopharmacological relevanceColitis is an important risk factor for the occurrence of colorectal cancer (CRC), and the colonization of Fusobacterium nucleatum (Fn) in the intestines accelerates this transformation process. Banxia Xiexin Decoction (BXD), originating from Shanghanlun, is a classic prescription for treating gastrointestinal diseases. Current researches indicate that BXD can effectively delay the colitis-to-cancer transition, but it is still unclear whether it can inhibit Fn colonization to achieve this delaying effect. Aim of studyThis study explored the effect and mechanism of BXD in inhibiting Fn intestinal colonization to delay colitis-to-cancer transition. Materials and methodsWe constructed a mouse model of colitis-to-cancer transition by regularly gavaging Fn combined with azoxymethane (AOM)/dextran sodium sulfate (DSS), and administered BXD by gavage. We monitored the body weight of mice, measured the length and weight of their colons, and calculated the disease activity index (DAI) score. The growth status of colon tumors was observed by hematoxylin and eosin (H&E) staining, and the changes in gut microbiota in each group of mice were detected by 16S rDNA analysis. Immunohistochemistry was used to detect the expression of E-cadherin and β-catenin in colon tissues, and immunofluorescence was used to observe the infiltration of M2 macrophages in colon tissues. In cell experiments, we established a co-culture model of Fn and colon cancer cells and intervened with BXD-containing serum. Malignant behaviors such as cell proliferation, invasion, and migration were detected, as well as changes in their cell cycle. We examined the protein levels of E-cadherin, β-catenin, Axin2, and Cyclin D1 in each group were detected by Western blot. We used US1 strain (fadA-) as a control and observed the effects of BXD-containing serum on Fn attachment and invasion of colon cancer cells through attachment and invasion experiments. ResultsBXD can inhibit the colitis-to-cancer transition in mice infected with Fn, reduce crypt structure damage, improve gut microbiota dysbiosis, upregulate E-cadherin and decrease β-catenin expression, and reduce infiltration of M2 macrophages, thus inhibiting the process of colitis-to-cancer transition. Cell experiments revealed that BXD-containing serum can inhibit the proliferation, migration, and invasion of colon cancer cells infected with Fn and regulate their cell cycle. More importantly, we found that BXD-containing serum can inhibit the binding of Fn's FadA adhesin to E-cadherin, reduce Fn's attachment and invasion of colon cancer cells, thereby downregulating the E-cadherin/β-catenin signaling pathway. ConclusionsThese findings show that BXD can inhibit Fn colonization by interfering with the binding of FadA to E-cadherin, reducing the activation of the E-cadherin/β-catenin signaling pathway, and ultimately delaying colitis-to-cancer transition.