Colon Cancer Prevention Research Articles

The Active Components in Whole Grain Wheat for Colon Cancer Prevention: Synergistic Effects Between Phytochemical Alkylresorcinols and Fiber Microbial Metabolite Butyrate

Abstract Objectives Wheat bran (WB) is a rich source of dietary fiber and phytochemicals with health-promoting properties. However, the active components especially the interaction between different components in whole grain (WG) wheat have not been fully explored. This study aimed to investigate whether WB phytochemicals, alkylresorcinols (ARs), and the active intestinal microbial metabolite of fiber, butyrate, could synergistically suppress human colon cancer cells. Methods Cell viability was determined by MTT assay in HCT-116 and HT-29 cells after the treatments of the combination of ARs, C21 and C19, and NaB, respectively. Apoptosis was determined by Cell Death ELISA Kit. The further mechanism was investigated by western blot associated with apoptosis, autophagy, and ER stress pathways. The C21 levels in gastrointestinal tract were measured by HPLC in mice treated with human-relevant doses of C21. Isobologram analysis was employed for the determination of synergistic or additive anticancer effects of the co-treatments of AR and NaB. Results The combination of C21 or C19 and butyrate synergistically inhibited the growth of colon cancer cells and induced apoptosis. Further mechanistic studies demonstrated that the co-treatment of C21 and butyrate induced significant upregulations in cleaved Poly(ADP-ribose) polymerase (PARP), cleaved caspase 3, p53 upregulated modulator of apoptosis (PUMA), cytochrome C, lipid-conjugated membrane-bound form of microtubule-associated protein 1A/1B-light chain 3 (LC3-II), and C/EBP homologous protein (CHOP) expressions. Notably, the C21 concentrations in the large intestinal tract of mice treated with human-relevant doses of C21, were from 0.86 to 1.78 μmol/g, suggesting the C21 doses used in vitro may be achievable after daily WG wheat intake. Conclusions We demonstrated for the first time that phytochemical component ARs and the microbial metabolites of WB fiber exhibit synergistic anticancer effects in human colon cancer cells, which may be associated with the induction of apoptosis, autophagy, and ER stress pathways. The present study provides novel insights into the understanding of the chemo-preventive effects of WG wheat against CRC. However, the mechanism of the synergistic anticancer effect of phytochemicals and fiber is complicated and still needs to be further investigated in vivo. Funding Sources USDA NIFA R01.

PCN211 BROADER COVERAGE OF CANCER PREVENTION IN THE US VS. EUROPE LEADS TO HIGHER COSTS AND BETTER OUTCOME

Between 3% and 35% of cancer deaths can be avoided by proper screening. However, using preventive protocols in large segment of population is associated with significant cost. We have investigated colon and breast cancer prevention and related cost and outcome comparing US and several countries in Europe (UK, Germany, Netherlands). Our initial assumption was that in countries with universal health coverage, cancer prevention would be widespread, and outcome would positively reflect the preventive measures.

Probiotic strain Lactobacillus plantarum YYC-3 prevents colon cancer in mice by regulating the tumour microenvironment

The gut microbiota plays important roles in chronic inflammation and colon cancer. Lactobacillus is a gut-resident probiotic with benefits to host health. We recently identified Lactobacillus plantarum strain YYC-3 with strong inhibition against two colon cancer cell lines (HT-29 and Caco2). However, the inhibitory effect of YYC-3 against colon cancer in vivo has not been verified. Thus, in the present study, we explored the probiotic function of strain YYC-3 and its cell-free supernatant (YYCS) respectively in the APCMin/+ mouse model of colon cancer during tumour development and growth, and the underlying anti-cancer mechanism. Treatment of both strain YYC-3 and the YYCS prevented the occurrence of colon tumours and mucosal damage in APCMin/+ mice fed a high-fat diet, although YYC-3 had a stronger anti-cancer effect. The mechanism involved modulation of the immune system and downregulated expression of the inflammatory cytokines interleukin (IL)-6, IL-17 F, and IL-22, along with reduced infiltration of inflammatory cells. Moreover, YYC-3 suppressed activation of the NF-κB and Wnt signalling pathways, and restored the altered gut microbiota composition to closely match that of wild-type mice. These results lay a theoretical foundation for application of YYC-3 in colon cancer prevention.

CD30L/CD30 signaling regulates the formation of the tumor immune microenvironment and inhibits intestinal tumor development of colitis-associated colon cancer in mice

Inflammatory bowel disease is one of the major causes of colitis-associated colon cancer (CAC). Therefore, it is necessary to explore new therapies to prevent colon cancer (CRC) in view of the relationship between chronic inflammation and tumor development. Previous studies on the correlation between CD30L/CD30 and cancer were mostly limited to lymphoid or homogenous tumors, while there have been only a few reports on the role of CD30L/CD30 signal transduction in the pathogenesis of CAC. In this study, we established an AOM/DSS-induced CAC model with CD30LKO mice to explore the effect of CD30L/CD30 signal transduction on the formation of the intestinal tumor immune microenvironment (TIME) during the development of intestinal tumors. Our results revealed that CD30L deficiency promoted the accumulation of myeloid derived suppressor cells (MDSCs), increased the expression of PD-L1 on MDSCs and tumor associated macrophages (TAMs), and enhanced the secretion of various inflammatory and immunosuppressive factors in the intestinal mucosa of CAC mice. Furthermore, CD30L gene deletion could selectively promote the upregulation of PD-1 expression on CD4+ and CD8+ T cells and inhibit their activation, differentiation and secretion of effector cytokines, which led to an attenuation of antitumor immune responses mediated by TEM (CD44+CD62L-) cells. Thus, our data suggest that CD30L/CD30 signaling might be a potential candidate target for immunological therapy in CAC.

A Survey on Machine Learning and Deep Learning-based Computer-Aided Methods for Detection of Polyps in CT Colonography.

Colon cancer generally begins as a neoplastic growth of tissue, called polyps, originating from the inner lining of the colon wall. Most colon polyps are considered harmless but over the time, they can evolve into colon cancer, which, when diagnosed in later stages, is often fatal. Hence, time is of the essence in the early detection of polyps and the prevention of colon cancer. To aid this endeavor, many computer-aided methods have been developed, which use a wide array of techniques to detect, localize and segment polyps from CT Colonography images. In this paper, a comprehensive state-of-the-art method is proposed and categorize this work broadly using the available classification techniques using Machine Learning and Deep Learning. The performance of each of the proposed approach is analyzed with existing methods and also how they can be used to tackle the timely and accurate detection of colon polyps.

Immunogenic cell death in colon cancer prevention and therapy.

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. The colonic mucosa constitutes a critical barrier and a major site of immune regulation. The immune system plays important roles in cancer development and treatment, and immune activation caused by chronic infection or inflammation is well-known to increase cancer risk. During tumor development, neoplastic cells continuously interact with and shape the tumor microenvironment (TME), which becomes progressively immunosuppressive. The clinical success of immune checkpoint blockade therapies is limited to a small set of CRCs with high tumor mutational load and tumor-infiltrating T cells. Induction of immunogenic cell death (ICD), a type of cell death eliciting an immune response, can therefore help break the immunosuppressive TME, engage the innate components, and prime T cell-mediated adaptive immunity for long-term tumor control. In this review, we discuss the current understanding of ICD induced by antineoplastic agents, the influence of driver mutations, and recent developments to harness ICD in colon cancer. Mechanism-guided combinations of ICD-inducing agents with immunotherapy and actionable biomarkers will likely offer more tailored and durable benefits to patients with colon cancer.

Pharmacist intervention in colorectal cancer screening initiative

ObjectivesTo assess the novel approach of using the community pharmacist as the primary health care team member to facilitate colorectal cancer (CRC) risk counseling and screening in socioeconomically disadvantaged populations. SettingA collaborative effort between the UConn Health Colon Cancer Prevention Program and UConn School of Pharmacy in conjunction with large independent chain pharmacies (medium to medium-high volume) located in metropolitan areas of Connecticut, including Hartford, Bridgeport, New Haven, and Stamford. Pharmacies located in hospitals, across the street from a large physician practice, or within the community. Practice descriptionThe study involved 2 phases. The first phase involved education and training for community pharmacists regarding counseling approaches for patients on the topic of CRC. The second phase of the study involved patient recruitment and counseling with subsequent fecal immunohistochemical testing (FIT). Practice innovationA community pharmacist provided face-to-face counseling on CRC risk factor reduction and provided CRC screening to patients who were without insurance or underinsured. No CRC screening or education program existed beforehand. EvaluationA target sample size of 60 participants was needed with a type 1 error rate of 5% and a power of 80%. Exploration of variables using multivariate logistic regression model included any variable with a univariate P < 0.2. Multivariate P values < 0.05 were considered independent predictors. ResultsAfter approaching 312 consumers, 16 of them consented to the study. The majority of participants (88%) were African American or Latino, and 69% were currently unemployed. Eight participants agreed to complete FIT, and 88% of participants completed FIT correctly. Only 1 positive FIT result was observed, but a subsequent colonoscopy was negative. Of the 12 questions that assessed baseline CRC knowledge in the initial survey, 16 participants answered an average of 2.6 (range, 0–6, SD, 1.6) questions incorrectly. Only 4 participants completed the follow-up survey of CRC knowledge and program satisfaction; thus, exploration of variables was not conducted. Patients indicated high satisfaction with the program of education and FIT dispensing. ConclusionThis study faced difficulty in recruiting pharmacists to participate, with the main reason being lack of compensation and disruption to workflow. Patient participation in the trial was also low because of a lack of time or interest in participation. Of the patients who did participate, the level of satisfaction in having the pharmacist speak to them about CRC screening was high. This service is an excellent example of how the pharmacist can provide a more accessible, convenient, and responsive approach to patients’ needs while improving health equity. Future studies that employ a revenue model to build the infrastructure and capacity necessary to offer this service efficiently and consistently are needed.

Evaluation of family health history collection methods impact on data and risk assessment outcomes.

Information technology applications for patient-collection of family health history (FHH) increase identification of elevated-risk individuals compared to usual care. It is unknown if the method of collection impacts data collected or if simply going directly to the patient is what makes the difference. The objective of this study was to examine differences in data detail and risk identification rates between FHH collection directly from individuals using paper-based forms and an interactive web-based platform. This is a non-randomized epidemiologic study in Singaporean population from 2016 to 2018. Intervention was paper-based versus web-based interactive platform for FHH collection. Participant demographics, FHH detail, and risk assessment results were analyzed. 882 participants enrolled in the study, 481 in the paper-based group and 401 in the web-based group with mean (SD) age of 45.4 (12.98) years and 47.5% male. Web-based FHH collection participants had an increased number of conditions per relative (p-value <0.001), greater frequency of reporting age of onset (p-value <0.001), and greater odds of receiving ≥1 risk recommendation both overall (OR: 3.99 (2.41, 6.59)) and within subcategories of genetic counselling for hereditary cancer syndromes (p-value = 0.041) and screening and prevention for breast (p-value = 0.002) and colon cancer (p-value = 0.005). This has significant implications for clinical care and research efforts where FHH is being assessed. Using interactive information technology platforms to collect FHH can improve the completeness of the data collected and result in increased rates of risk identification. Methods of data collection to maximize benefit should be taken into account in future studies and clinical care.

Pediatric Colonoscopic Polypectomy Technique.

Colonoscopy with polypectomy is frequently performed in pediatric patients based on symptoms, with the majority of polyps identified being benign juvenile pedunculated polyps with a vascular stalk. This is in distinction to adults where polypectomy is often performed as part of a colon cancer screening and prevention strategy and a higher fraction of polyps are sessile and or dysplastic. In adults, polypectomy techniques emphasize a need for deeper resection to ensure complete resection of adenomas or potential carcinoma in situ. Adenomatous polyps can occur in the pediatric age group and may be associated with an underlying polyposis, hereditary or chronic inflammatory conditions. Polypectomy techniques include use of cold biopsy forceps for very small polyps, cold snare polypectomy for small sessile polyps and hot snare polypectomy for the majority of polyps in the pediatric age group. Adjuvant techniques include epinephrine volume reduction, saline-assisted polypectomy and hemostatic techniques including injection, clip application and loop application to prevent or treat post-polypectomy bleeding. Electrosurgical principles guide the settings and type of current utilized during hot snare polypectomy. Polypectomy utilizing thermal techniques is associated with a higher risk of complications compared with diagnostic colonoscopy.

화학적 발암원을 투여한 마우스 모델에서 규칙적인 유산소운동의 대장암 형성 억제효과

We investigated the effect of regular aerobic exercise on colon tumorigenesis associated with inflammatory factors, such as interleukin-1β(IL-1β), interleukin-6 (IL-6), monocyte chemoatractant protein-1 (MCP-1) and tumor necrosis factor-α(TNF-α), in azoxymethan/dextran sulfate sodium (AOM/DSS) -administrated mice. ICR mice (5 weeks o ld) were divided into three g roups of 10 animals each, consisting of a control group (CON), an AOM/DSS treatment group (AOM/DSS), and an AOM/DSS treatment plus exercise group (AOM/DSS+Ex). The AOM/DSS+Ex group performed five times per week, for a total of 45 minutes, at a speed of 20 m per minute, using a treadmill with a gradient of 5% for 12 weeks. To investigate the effects of regular aerobic exercises on inflammation and formation of colorectal cancer, we carried out colorectal histopathologic analysis, colon tumor number counting and tumor-related inflammatory cytokine analysis. The number of colon tumors in the AOM/DSS+Ex group was approximately 25% lower than in the AOM/DSS group, but no statistically significant. In colon weight and length, there was no significantly difference between AOM/DSS group and AOM/DSS+Ex group. On the other hand, there were significant reductions in tumor-related inflammatory cytokines, IL-6 and TNF-α(P＜.05) between AOM/DSS group and AOM/DSS+Ex group, but not in IL-1β and MCP-1. In conclusion, this exercise protocol resulted in partial anti-inflammatory and -tumor effects. Therefore, it is necessary to carry out further studies by diverse exercise protocols to establish colon cancer prevention program.

A qualitative study of patient preferences for prompts and reminders for a direct-mail fecal testing program.

Programs that directly mail fecal immunochemical tests (FIT) to patients can increase colorectal cancer (CRC) screening, especially in low-income and Latino populations. Few studies have explored patient reactions to prompts or reminders that accompany such programs. As part of the Participatory Research to Advance Colon Cancer Prevention pilot study, which tested prompts and reminders to a direct-mail FIT program in a large, urban health center, we conducted telephone interviews among English- and Spanish-speaking participants who were assigned to receive a series of text message prompts, automated phone call reminders, and/or live phone call reminders. We analyzed interviews using a qualitative content analysis approach. We interviewed 41 participants, including 25 responders (61%) and 16 nonresponders (39%) to the direct-mail program. Participants appreciated program ease and convenience. Few participants recalled receiving prompts or automated/live reminders; nevertheless, the vast majority (95%, n = 39) thought reminders were acceptable and helpful and suggested that 2-3 reminders delivered starting 1 week after the mailed FIT would optimally encourage completion. Prompts and reminders used with mailed-FIT programs are accepted by patients, and my help boost response rates.

Propolis prevents inhibition of apoptosis by potassium bromate in CCD 841 human colon cell.

Previously, we demonstrated that biotransformation of propolis by some special strains of Lactobacillus plantarum might decrease the allergenic molecules in propolis. In this study, we aimed to investigate the effect of biotransformation of propolis on its antioxidant effect and its protective effect against potassium bromate-induced cancer in human colon cell line. Propolis samples were treated with different solutions (ethanol, polyethylene glycol, and water), and ultrasonication was applied at 40 Hz (5, 10, and 15 minutes) in order to facilitate solvation of solid samples. Fermentations were performed by L. plantarum strains (ISLG-2, ATCC-8014, and Visbyvac). The phenolic content of propolis was determined with liquid chromatography-mass spectrometry/mass spectrometry (LCMS/MS). The antioxidant activity (antioxidant enzymes, lipid peroxidation) and apoptosis markers (caspase 3,8,9, cytochrome-c, tumour necrosis factor-related apoptosis-inducing ligand-R1 and R2 [TRAIL], and apoptosis protease activating factor-1 [APAF-1] levels) were determined in CCD 841-human colon cell line after induction of oxidative stress by potassium bromate. All propolis samples in different solvents induced apoptosis and 4 biotransformed (by L. plantarum ISL-2 strain and L. plantarum ATCC 8014 strain) propolis samples with low allergenic molecules demonstrated similar inductions of apoptosis in CCD841 cell line. In conclusion, reduction of allergenic molecules in propolis via biotransformation did not change the antioxidant and protective effects of propolis, and it is suggested as a potential therapeutic molecule in prevention of colon cancer caused by oxidative stress for all patients. SIGNIFICANCE OF THE STUDY: This study is the first investigation that shows protective effect of propolis against potassium bromate toxicity by means of decreasing lipid peroxidation and reversing the main molecule levels in intrinsic and extrinsic pathway of apoptosis. Biotransformed propolis samples by L. plantarum ISL-2 and ATCC 8014 strain with low allergen molecule content has also the same effect in potassium bromate toxicity in CCD841 colon cell. Our data contributed that propolis as a natural compound might be a good candidate due to its minimal toxicity and lack of any adverse effects to prevent carcinogenic effect of potassium bromate.

Methanol Extract of Coleus amboinicus (Lour) Exhibited Antiproliferative Activity and Induced Programmed Cell Death in Colon Cancer Cell WiDr.

Coleus amboinicus(Lour) (CA) has been reported to possess many pharmacological activities. In this study, evaluation of cytotoxicity using brine shrimp lethality bioassay and MTT assay using WiDr cell lines was carried out. The expression of several genes responsible for programmed cell death of the methanol extract of CA was also investigated. The morphology of the cells undergoing apoptosis was detected using Hoechst staining assay. The gene expression of BAX, BCL2, P53, Caspase 1, 7, 8, and 9 of treated samples with different concentrations (10, 15, 25 & 50 µg/ml) were measured with RT PCR. The phytochemical profiles were investigated using LC MS. The results showed that the lethality concentration (LC50) of methanol extract using brine shrimp was 34.545 µg/ml and the extract exhibited good antiproliferative activity against cancer cells WiDr with IC50 value (8.598 ± 2.68 µg/ml) as compared to standard drug 5-fluorouracil (IC50 value 1.839 ± 0.03 µg/ml). There was apoptotic evidences from the morphology of treated cells. The expressions of BAX,P53, and Caspase 9 were upregulated in lower concentration of the extract (10 and 15 µg/ml) but downregulated in higher concentration (25 and 50 µg/ml). BCL2 as anti-apoptotic gene was downregulated in all concentrations. Caspase 1 and Caspase 7 were upregulated in high concentration (25 and 50 µg/ml), but downregulated in lower concentrations. These data provide a mode of cell death for the methanol extract of CA in low concentrations corresponding to apoptosis with intrinsic pathway. Many valuable compounds identified including caffeic acid, rosmarinic acid, malic acid, eicosapentanoic acid, benserazide, alpha-linolenic acid, betaine, Salvanolic B, 4-hydroxibenzoic acid and firulic acid have been previously reported as being active agents against many cancer cells. This study suggested that CA might become an effective ingredient for health-beneficial foods to prevent colon cancer.

Encapsulation of phycocyanin by prebiotics and polysaccharides-based electrospun fibers and improved colon cancer prevention effects

To preserve bioactivity and achieve colon targeted release of phycocyanin (PC), the polysaccharides-based electrospun fiber mat (EFM) containing PC and prebiotics was prepared and characterized. In vitro release tests confirmed the colon targeting behavior of PC, in particular, faster release of PC was achieved due to the addition of prebiotics. Ritger–Peppas model confirmed that the release of PC in simulated colon fluids follows a mechanism of anomalous transport (non-Fickian). CCK-8 results showed that the combination of PC and prebiotics exerted a significant anti-proliferative effect on HCT116 cells with an IC50 values of 22.31, 17.12 and 11.63 mg/mL after 24, 48, and 72 h, respectively. Furthermore, the cell cycle and apoptosis analysis revealed that the inhibition activity on HCT116 cells was caused by arresting cell cycle at G0/G1 phase that is relevant to the inhibition of cyclin D1 and CDK4 and the up-regulation of p21 expression, and inducing cell apoptosis by mediating the mitochondrial pathway as well, in which the decrease of Bcl-2/Bax, activation of caspase 3 and release of cytochrome c were included. This study suggests that the PC-loaded EFM with GOS holds a great potential as an effective formulation for colon cancer prevention.

Selective Targeting of Cancer Stem Cells (CSCs) Based on Photodynamic Therapy (PDT) Penetration Depth Inhibits Colon Polyp Formation in Mice.

Targeting cancer stem cells (CSCs) without damaging normal stem cells could contribute to the development of novel radical cancer therapies. Cells expressing leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) constitute a cancer-causing population in the colon; therefore, targeting of Lgr5+ cells is expected to provide an opportunity to mitigate colon cancer. However, the expression of Lgr5 in normal stem cells makes it difficult to prove the efficacy of therapies targeted exclusively at Lgr5+ cancer cells. We used a modified photodynamic therapy technique involving cellular radiative transfer between green fluorescent protein (GFP)-expressing cells and a rose bengal photosensitizer. After treatment, tumors containing GFP-Lgr5+ cells were observed to be significantly suppressed or retarded with little effect on GFP-Lgr5+ stem cells at the crypt bottom. Lgr5+ CSCs were specifically eradicated in situ, when localized based on the depth from the colon lumen, revealing the potential preventive efficacy of Lgr5-targeted therapy on tumor growth. This study supports the idea that Lgr5+ cells localized near the colon luminal surface are central to colorectal cancer. With further development, the targeting of localized Lgr5+ cancer stem cells, which this study demonstrates in concept, may be feasible for prevention of colon cancer in high-risk populations.

Cyanidin-3-glucoside binds to talin and modulates colon cancer cell adhesions and 3D growth.

Cyanidin-3-glucoside (C3G) is a natural pigment, found in many colorful fruits and vegetables. It has many health benefits, including anti-inflammation, cancer prevention, and anti-diabetes. Although C3G is assumed to be an antioxidant, it has been reported to affect cell-matrix adhesions. However, the underlying molecular mechanism is unknown. Here, we show that the expression of talin1, a key regulator of integrins and cell adhesions, negatively correlated with the survival rate of colon cancer patients and that depletion of talin1 inhibited 3D spheroid growth in colon cancer cells. Interestingly, C3G bound to talin and promoted the interaction of talin with β1A-integrin. Molecular docking analysis shows that C3G binds to the interface of the talin-β-integrin complex, acting as an allosteric regulator and altering the interaction between talin and integrin. Moreover, C3G promoted colon cancer cell attachment to fibronectin. While C3G had no significant effect on colon cancer cell proliferation, it significantly inhibited 3D spheroid growth in fibrin gel assays. Since C3G has no or very low toxicity, it could be potentially used for colon cancer prevention or therapy.

Multitarget stool DNA testing for the prevention of colon cancer: outcomes in a large integrated healthcare system

Multitarget stool DNA (MT-sDNA) testing is used in primary care as a screening test for colon cancer. Test effectiveness and patient compliance were examined in clinical practice. We assessed outcomes of MT-sDNA testing in a cohort study conducted in a large integrated healthcare system comprising 15 hospitals and 150 outpatient clinics using advanced electronic data capture (Clarity2 [Epic, Verona, Wisc, USA] and REDCap [Encinitas, Calif, USA]) followed by manual chart review to confirm MT-sDNA test results and to monitor the outcomes of subsequent colonoscopy. A total of 6835 MT-sDNA tests were performed over 1 year between 2017 and 2018. Of 1242 patients (18%) who tested positive, 1109 (89%) were referred for colonoscopy, and 905 of them (73%) underwent colonoscopy. Eleven patients (<1%) with a positive test had colorectal cancer, 215 (17%) had advanced adenomas, 110 (9%) had serrated adenomas, and 546 (60%) patients had an adenoma. Of the 6835 patients tested, adenoma or cancer was found in 557 patients (8%). An advanced adenoma or cancer was found in 226 of 1242 patients with a positive test (18%). Nonadherence with colonoscopy after a positive test was high (21%), and the cost to detect 1 advanced adenoma or cancer was $38,849. The frequency of adenoma detection by an MT-sDNA screening strategy is low, and many positive tests are not associated with significant findings at colonoscopy. Failure to follow a positive test with colonoscopy is a significant problem that needs to be considered when this screening strategy is adopted.

The Relationship between Prevention and Treatment of Colorectal Cancer and Cancerous Toxin Pathogenesis Theory Basing on Gut Microbiota.

Gut microbiota is a diverse consortium of bacteria, fungi, protozoa, and viruses in the gut of all mammals. Gut microbiota remains in steady state under normal conditions. Changes in the internal and external environment may cause gut Microbiota to be out of tune. Malignant tumors are one of the major diseases currently endangering human health. CRC (colorectal cancer) has a significant upward trend in morbidity and mortality in many parts of the world. Technological advances have not yet brought about a breakthrough in the efficacy of CRC. The development of colon cancer is closely related to gut microbiota imbalance. According to more than 60 years of clinical practice, Professor Zhongying Zhou first proposed the pathogenesis theory of “cancerous toxin” in the 1990s and believed that cancerous toxin was a key pathogenesis of tumor development. Under the guidance of the theory of cancerous toxin, combined with clinical practice, Professor Zhou created an effective anticancer Chinese herbal compound, Jiedu Xiaoai Prescription. This paper summarizes recent hotspots related to gut microbiota and the occurrence, development, and prevention of colon cancer at home and abroad. The relationship between gut microbiota and cancerous toxin theory is proposed, and the feasibility of further studying the biological basis of cancerous toxin pathogenesis theory from the perspective of gut microbiota is pointed out.

Colon Cancer Prevention with Walnuts: A Longitudinal Study in Mice from the Perspective of a Gut Enterotype-like Cluster.

There is limited understanding of how walnut consumption inhibits the development of colorectal cancer. A possible mechanism may involve alterations to the gut microbiota. In this study, the effects of walnut on gut microbiota were tested in a mouse tumor bioassay using the colonotropic carcinogen, azoxymethane (AOM) added to the total Western diet (TWD). 16S rRNA pyrosequencing identified three enterotype-like clusters (E1, E2, and E3) in this murine model. E1, E2, and E3 are associated with AOM exposure, walnut consumption, and TWD diet, respectively. E2 and E3 showed distinct taxonomic and functional characteristics, while E1 represented an intermediate state. At the family level, E1 and E3 were both enriched with Bacteroidaceae, but driven by two different operational taxonomic units (OTU; OTU-2 for E1, OTU-4 for E3). E2 was overrepresented with Porphyromonadaceae and Lachnospiraceae, with OTU-3 (family Porphyromonadaceae) as the "driver" OTU for this cluster. Functionally, E3 is overrepresented with genes of glycan biosynthesis and metabolism, xenobiotic metabolism, and lipid metabolism. E2 is enriched with genes associated with cell motility, replication and repair, and amino acid metabolism. Longitudinally, E2 represents the gut microbial status of early life in these mice. In comparison with E1 and E3, E2 is associated with a moderate lower tumor burden (P = 0.12). Our results suggest that walnuts may reduce the risk of colorectal cancer within a Western diet by altering the gut microbiota. Our findings provide further evidence that colorectal cancer risk is potentially modifiable by diet via alterations to the microbiota.

Electrosprayed highly cross-linked arabinoxylan particles: effect of partly fermentation on the inhibition of Caco-2 cells proliferation

<abstract> Arabinoxylans (AX) are gelling polysaccharides with potential applications as colon-targeted biomaterials. Nevertheless, the fermentation of highly cross-linked AX particles (AXP) by colonic bacteria and the effect of its fermentation supernatants on the proliferation of human colon cancer cells have not been investigated so far. In this study, electrosprayed AXP were fermented by <italic>Bifidobacterium longum</italic>, <italic>Bifidobacterium adolescentis</italic>, and <italic>Bacteroides ovatus</italic>. The effect of AXP fermentation supernatant (AXP-fs) on the inhibition of the human colon cancer cell line Caco-2 proliferation was investigated. AXP presented a mean diameter of 533 µm, a spherical shape, and a cross-linking content (dimers and trimers of ferulic acid) of 1.65 µg/mg polysaccharide. After 48 h of bacteria exposure, AXP were only partly fermented, probably due to polymeric network steric hindrance that limits the access of bacterial enzymes to the polysaccharide target sites. AXP partial fermentation was evidenced by a moderate short-chain fatty acid production (SCFA) (23 mM) and a collapsed and disintegrated microstructure revealed by scanning electron microscopy. AXP-fs exerted slight inhibition of Caco-2 cell proliferation (11%), which could be attributed to the SCFA generated during partly polysaccharide fermentation. These findings indicate that electrosprayed AXP are a slow-fermentable biomaterial presenting slight anti-cancer properties and potential application in colon cancer prevention. </abstract>