A two-front nutritional environment fuels colorectal cancer: perspectives for dietary intervention

2021 ◽  
Author(s):  
Elien Alderweireldt ◽  
Charlotte Grootaert ◽  
Olivier De Wever ◽  
John Van Camp
Keyword(s):  
Colorectal Cancer ◽  
Dietary Intervention ◽  
Nutritional Environment

scholarly journals Resistant starch supplementation increases crypt cell proliferative state in the rectal mucosa of older healthy participants

2020 ◽  
Vol 124 (4) ◽  
pp. 374-385
Author(s):  
Fiona C. Malcomson ◽  
Naomi D. Willis ◽  
Iain McCallum ◽  
Long Xie ◽  
Arthur C. Ouwehand ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Resistant Starch ◽  
Dietary Intervention ◽  
Controlled Trial ◽  
Rectal Mucosa ◽  
Crypt Cell ◽  
Post Intervention ◽  
Double Blind ◽  
Healthy Participants

AbstractThere is strong evidence that foods containing dietary fibre protect against colorectal cancer, resulting at least in part from its anti-proliferative properties. This study aimed to investigate the effects of supplementation with two non-digestible carbohydrates, resistant starch (RS) and polydextrose (PD), on crypt cell proliferative state (CCPS) in the macroscopically normal rectal mucosa of healthy individuals. We also investigated relationships between expression of regulators of apoptosis and of the cell cycle on markers of CCPS. Seventy-five healthy participants were supplemented with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design in a randomised, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study). CCPS was assessed, and the expression of regulators of the cell cycle and of apoptosis was measured by quantitative PCR in rectal mucosal biopsies. SCFA concentrations were quantified in faecal samples collected pre- and post-intervention. Supplementation with RS increased the total number of mitotic cells within the crypt by 60 % (P = 0·001) compared with placebo. This effect was limited to older participants (aged ≥50 years). No other differences were observed for the treatments with PD or RS as compared with their respective controls. PD did not influence any of the measured variables. RS, however, increased cell proliferation in the crypts of the macroscopically-normal rectum of older adults. Our findings suggest that the effects of RS on CCPS are not only dose, type of RS and health status-specific but are also influenced by age.

scholarly journals Black Raspberries Suppress Colorectal Cancer by Enhancing Smad4 Expression in Colonic Epithelium and Natural Killer Cells

2020 ◽  
Vol 11 ◽  
Author(s):  
Yi-Wen Huang ◽  
Chien-Wei Lin ◽  
Pan Pan ◽  
Tianjiao Shan ◽  
Carla Elena Echeveste ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Nk Cells ◽  
Natural Killer ◽  
Dietary Intervention ◽  
Nk Cell ◽  
Good Prognosis ◽  
Colonic Epithelium ◽  
Antitumor Effects ◽  
Black Raspberries ◽  
Smad4 Expression

Innate immune cells in the tumor microenvironment have been proposed to control the transition from benign to malignant stages. In many cancers, increased infiltration of natural killer (NK) cells associates with good prognosis. Although the mechanisms that enable NK cells to restrain colorectal cancer (CRC) are unclear, the current study suggests the involvement of Smad4. We found suppressed Smad4 expression in circulating NK cells of untreated metastatic CRC patients. Moreover, NK cell-specific Smad4 deletion promoted colon adenomas in DSS-treated ApcMin/+ mice and adenocarcinomas in AOM/DSS-treated mice. Other studies have shown that Smad4 loss or weak expression in colonic epithelium associates with poor survival in CRC patients. Therefore, targeting Smad4 in both colonic epithelium and NK cells could provide an excellent opportunity to manage CRC. Toward this end, we showed that dietary intervention with black raspberries (BRBs) increased Smad4 expression in colonic epithelium in patients with FAP or CRC and in the two CRC mouse models. Also, benzoate metabolites of BRBs, such as hippurate, upregulated Smad4 and Gzmb expression that might enhance the cytotoxicity of primary human NK cells. Of note, increased levels of hippurate is a metabolomic marker of a healthy gut microbiota in humans, and hippurate also has antitumor effects. In conclusion, our study suggests a new mechanism for the action of benzoate metabolites derived from plant-based foods. This mechanism could be exploited clinically to upregulate Smad4 in colonic epithelium and NK cells, thereby delaying CRC progression.

Nutritional genomics: the next frontier in the postgenomic era

2004 ◽  
Vol 16 (2) ◽  
pp. 166-177 ◽  
Author(s):  
Jim Kaput ◽  
Raymond L. Rodriguez
Keyword(s):  
Gene Expression ◽  
Chronic Disease ◽  
Dietary Intervention ◽  
Molecular Genetic ◽  
Genomic Research ◽  
Nutritional Requirement ◽  
Disease States ◽  
Nutritional Environment ◽  
Nutritional Genomics ◽  
Genetic Makeup

The interface between the nutritional environment and cellular/genetic processes is being referred to as “nutrigenomics.” Nutrigenomics seeks to provide a molecular genetic understanding for how common dietary chemicals (i.e., nutrition) affect health by altering the expression and/or structure of an individual’s genetic makeup. The fundamental concepts of the field are that the progression from a healthy phenotype to a chronic disease phenotype must occur by changes in gene expression or by differences in activities of proteins and enzymes and that dietary chemicals directly or indirectly regulate the expression of genomic information. We present a conceptual basis and specific examples for this new branch of genomic research that focuses on the tenets of nutritional genomics: 1) common dietary chemicals act on the human genome, either directly or indirectly, to alter gene expression or structure; 2) under certain circumstances and in some individuals, diet can be a serious risk factor for a number of diseases; 3) some diet-regulated genes (and their normal, common variants) are likely to play a role in the onset, incidence, progression, and/or severity of chronic diseases; 4) the degree to which diet influences the balance between healthy and disease states may depend on an individual’s genetic makeup; and 5) dietary intervention based on knowledge of nutritional requirement, nutritional status, and genotype (i.e., “individualized nutrition”) can be used to prevent, mitigate, or cure chronic disease.

scholarly journals Black Raspberry Supplementation Alters the Gut Microbiome and Improves Alpha Diversity in a Mouse Model of Inflammation-Associated Colorectal Cancer

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1177-1177
Author(s):  
Daphne Rodriguez ◽  
Eliza Owens ◽  
Sam Vassar ◽  
Ashley Bartlett ◽  
Emily Mortensen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiome ◽  
Dietary Intervention ◽  
Alpha Diversity ◽  
Basal Diet ◽  
Recovery Phase ◽  
Protective Effects ◽  
Linear Discriminant ◽  
Microbiome Composition ◽  
Freeze Dried

Abstract Objectives Anti-inflammatory bioactives in black raspberries (BRB) have been shown to have protective effects on the colon epithelium and may influence gut microbiome. The goal of this study was to determine the effects of dietary intervention with BRB on the dynamic composition of the gut microbiome composition in mice. Methods Using a 2 × 2 factorial design, C57BL/6J male mice were fed the standard AIN93G diet or the total Western diet (TWD) for 16 weeks with or without 10% (w/w) whole, freeze-dried BRB powder. The azoxymethane + dextran sodium sulfate model of inflammation-associated colorectal cancer was employed to assess the dynamic response of the gut microbiome to basal diet and BRB treatment prior to, during, and after active colitis and at the study end. Microbiome composition was determined using 16s rRNA sequencing followed by diversity analyses (alpha and beta) and identification of discriminating taxa by with linear discriminant analyses by effect size (lefse). Results Alpha diversity was markedly reduced during colitis for mice consuming either AIN93G or TWD, with some improvement noted by the recovery phase. Of note, consumption of BRB for two weeks significantly increased alpha diversity measures, and BRB improved alpha diversity in mice fed the AIN93G diet during colitis. Alternatively, BRB appeared less effective in mice fed TWD. Beta diversity was also significantly affected with notable clustering of microbiomes by BRB treatment during and after colitis. Consumption of BRB affected the relative abundance of several key taxa over the course of colitis and recovery from gut injury, including Erysipelotrichaceae, Bifidobacteriaceae, Streptococcaceae, Rikenellaceae, Ruminococcaceae and Akkermansiaceae, among others. Conclusions Dietary supplementation with BRB shifted the composition of the gut microbiome during colitis and recovery from gut injury, though the effects were inconsistent with respect to the basal diet consumed. Funding Sources USDA NIFA AFRI grant no. 2018-67017-27,516 and 2014-67017-21755.

A pilot study to determine the feasibility of a customized low glycemic load diet in patients with stage I-III colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4643-4643
Author(s):  
Michelle Elizabeth Treasure ◽  
Alicia Thomas ◽  
Stephen Ganocy ◽  
Augustine Hong ◽  
Smitha S. Krishnamurthi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pilot Study ◽  
Dietary Intervention ◽  
Dietary Habits ◽  
Glycemic Load ◽  
Stage I ◽  
Cancer Outcomes ◽  
Glycemic Indices ◽  
Metabolic Indices ◽  
The Impact

4643 Background: Observational evidence associates energy balance factors, particularly diet, with survival in patients with colorectal cancer (CRC). Consumption of a diet with high glycemic indices has been associated with inferior cancer-specific outcomes, but there is limited prospective evidence that alterations in dietary habits improve cancer outcomes. This was a pilot study to determine the feasibility and acceptability of following a low glycemic load (GL) diet in patients with stage I-III CRC and to assess the nutritional resources necessary to follow the diet. Methods: 18 patients with stage I-III CRC, who completed definitive cancer therapy and consumed an avg daily GL > 150 participated in a 12 week, tailored, in-person dietary intervention with a target GL of ≤102. Compliance was assessed using 24 hour telephone recalls. Acceptability of the diet was assessed using a food acceptability questionnaire, and exploratory correlative laboratories were assessed monthly. Results: 67% of patients were compliant with a low GL diet ≥ 75% of the time, over a 12 week time period. Majority of participants experienced a decrease in BMI and waist circumference, 28% experienced meaningful weight loss defined as ≥ 5%. The nutritionist spent an avg of 6.97 hours (SD 2.18) in-person and 1.58 hours (SD 0.68) by phone with each participant. In the overall group, significant decreases were seen in total cholesterol (7.2% decrease; t = -2.33, p = 0.03), VLDL (26.8% decrease; t = -2.33, p = 0.03) and triglycerides (26.6% decrease; t = -2.29; p = 0.04). All participants were satisfied with the diet; 43% were extremely satisfied. 75% of participants liked the foods they were able to eat “very much” or “extremely”. All participants felt the in-person meetings were helpful. 77% did not feel an online video could replace the in-person meetings. 62% of participants did not feel a virtual meeting (e.g skype, etc.) could replace the in- person meeting while 38% felt it could. Conclusions: Patients with stage I-III CRC are able to follow a low GL diet with an in-person dietary intervention. Significant decreases in laboratory measures confirm the efficacy of the diet in altering metabolic indices. All participants who completed the study were satisfied with the diet, the majority of whom enjoyed the foods and planned to continue to follow the diet after study completion. The majority felt in-person contact with the nutritionist was essential to their success. This study was an essential step in designing a larger scale trial to evaluate the impact of low GL diet on cancer outcomes. Clinical trial information: NCT02129218 .

scholarly journals Effects of a Rice Bran Dietary Intervention on the Composition of the Intestinal Microbiota of Adults with a High Risk of Colorectal Cancer: A Pilot Randomised-Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 526
Author(s):  
Winnie K. W. So ◽  
Judy Y. W. Chan ◽  
Bernard M. H. Law ◽  
Kai Chow Choi ◽  
Jessica Y. L. Ching ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Intestinal Microbiota ◽  
Rice Bran ◽  
Dietary Intervention ◽  
Controlled Trial ◽  
Intervention Group ◽  
Control Group ◽  
Intestinal Health ◽  
Health Promoting

Rice bran exhibits chemopreventive properties that may help to prevent colorectal cancer (CRC), and a short-term rice bran dietary intervention may promote intestinal health via modification of the intestinal microbiota. We conducted a pilot, double-blind, randomised placebo-controlled trial to assess the feasibility of implementing a long-term (24-week) rice bran dietary intervention in Chinese subjects with a high risk of CRC, and to examine its effects on the composition of their intestinal microbiota. Forty subjects were randomised into the intervention group (n = 19) or the control group (n = 20). The intervention participants consumed 30 g of rice bran over 24-h intervals for 24 weeks, whilst the control participants consumed 30 g of rice powder on the same schedule. High rates of retention (97.5%) and compliance (≥91.3%) were observed. No adverse effects were reported. The intervention significantly enhanced the intestinal abundance of Firmicutes and Lactobacillus, and tended to increase the Firmicutes/Bacteroidetes ratio and the intestinal abundance of Prevotella_9 and the health-promoting Lactobacillales and Bifidobacteria, but had no effect on bacterial diversity. Overall, a 24-week rice bran dietary intervention was feasible, and may increase intestinal health by inducing health-promoting modification of the intestinal microbiota. Further larger-scale studies involving a longer intervention duration and multiple follow-up outcome assessments are recommended.

scholarly journals Colorectal Cancer in Africa: Causes, Dietary Intervention, and Lifestyle Change

2021 ◽  
Vol 6 (4) ◽  
pp. 21-34
Author(s):  
Oluwatoyin B. Oluwole ◽  
Viola A. Nwachukwu Nicholas-Okpara ◽  
Elemo Gloria ◽  
Deborah Ibekwe ◽  
Ijeoma Eboagwu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dietary Intervention ◽  
Lifestyle Modification ◽  
Whole Grains ◽  
Processed Meat ◽  
Protective Effects ◽  
Global Public Health ◽  
Environmental Carcinogens ◽  
Dietary Choices ◽  
Refined Carbohydrates

Colorectal cancer (CRC) is a menace in the global public health system. According to GLOBOCAN reports, colorectal cancer is the second most diagnosed cancer in the world with more than 1.9 million cases and 935,000 deaths in 2020 alone. Diet plays a key role in exposing humans to environmental carcinogens and anti-carcinogens, consequently mitigating or aiding in the development of various cancers. CRC is most prevalent in western countries with a high intake of saturated fats, refined carbohydrates, and processed meat. CRC was an extremely rare disease in Africa some decades ago, but the situation is fast changing. The traditional African diet consists of leafy, roots and cruciferous vegetables, fruits, roots, tubers and plantains, legumes, whole grains, and spices, all of which have been shown to possess protective effects against CRC. However, the effect of urbanization has contributed to the shift of dietary choices among the African population to consuming more ultra-processed foods with high levels of unhealthy components that have originated from colorectal cancer prevalent regions. This review evaluates the current nutritional challenges of the African diet to colorectal cancer and the potential roles of the traditional African diets and lifestyle modification in the prevention and management of colorectal cancer.

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