Consumption of Black Raspberries Altered the Composition of the Fecal Microbiome in Mice Fed a Western Type Diet (OR04-01-19)

Dietary strategies to reduce colonic inflammation and promote gut homeostasis may markedly reduce the risk of colitis-associated colorectal cancer. Previously, we showed that dietary supplementation with black raspberries significantly suppressed colitis and colon tumorigenesis promoted by the consumption a Western type diet in mice. In this study, our goal was to assess the impact of consumption of the TWD with and without black raspberry supplementation on the composition of the fecal microbiome over the course of disease development

Basal Diet Determined Long-Term Composition of the Gut Microbiome and Mouse Phenotype to a Greater Extent than Fecal Microbiome Transfer from Lean or Obese Human Donors

The Western dietary pattern can alter the gut microbiome and cause obesity and metabolic disorders. To examine the interactions between diet, the microbiome, and obesity, we transplanted gut microbiota from lean or obese human donors into mice fed one of three diets for 22 weeks: (1) a control AIN93G diet; (2) the total Western diet (TWD), which mimics the American diet; or (3) a 45% high-fat diet-induced obesity (DIO) diet. We hypothesized that a fecal microbiome transfer (FMT) from obese donors would lead to an obese phenotype and aberrant glucose metabolism in recipient mice that would be exacerbated by consumption of the TWD or DIO diets. Prior to the FMT, the native microbiome was depleted using an established broad-spectrum antibiotic protocol. Interestingly, the human donor body type microbiome did not significantly affect final body weight or body composition in mice fed any of the experimental diets. Beta diversity analysis and linear discriminant analysis with effect size (LEfSe) showed that mice that received an FMT from obese donors had a significantly different microbiome compared to mice that received an FMT from lean donors. However, after 22 weeks, diet influenced the microbiome composition irrespective of donor body type, suggesting that diet is a key variable in the shaping of the gut microbiome after FMT

Consumption of the Total Western Diet Promotes Colitis and Inflammation-Associated Colorectal Cancer in Mice

Consumption of a Western type diet is a known risk factor for colorectal cancer. Our group previously developed the total Western diet (TWD) for rodents with energy and nutrient profiles that emulate a typical Western diet. In this study, we tested the hypothesis that consumption of the TWD would enhance colitis, delay recovery from gut injury and promote colon tumorigenesis. In multiple experiments using the azoxymethane + dextran sodium sulfate or ApcMin/+ mouse models of colitis-associated colorectal carcinogenesis (CAC), we determined that mice fed TWD experienced more severe and more prolonged colitis compared to their counterparts fed the standard AIN93G diet, ultimately leading to markedly enhanced colon tumorigenesis. Additionally, this increased tumor response was attributed to the micronutrient fraction of the TWD, and restoration of calcium and vitamin D to standard amounts ameliorated the tumor-promoting effects of TWD. Finally, exposure to the TWD elicited large scale, dynamic changes in mRNA signatures of colon mucosa associated with interferon (IFN) response, inflammation, innate immunity, adaptive immunity, and antigen processing pathways, among others. Taken together, these observations indicate that consumption of the TWD markedly enhanced colitis, delayed recovery from gut injury, and enhanced colon tumorigenesis likely via extensive changes in expression of immune-related genes in the colon mucosa

Sustainable and Equitable Increases in Fruit and Vegetable Productivity and Consumption are Needed to Achieve Global Nutrition Security

Increased intake of fruits and vegetables (F&V) is recommended for most populations across the globe. However, the current state of global and regional food systems is such that F&V availability, the production required to sustain them, and consumer food choices are all severely deficient to meet this need. Given the critical state of public health and nutrition worldwide, as well as the fragility of the ecological systems and resources on which they rely, there is a great need for research, investment, and innovation in F&V systems to nourish our global population. Here, we review the challenges that must be addressed in order to expand production and consumption of F&V sustainably and on a global scale. At the conclusion of the workshop, the gathered participants drafted the “Aspen/Keystone Declaration” (see below), which announces the formation of a new “Community of Practice,” whose area of work is described in this position paper. The need for this work is based on a series of premises discussed in detail at the workshop and summarized herein. To surmount these challenges, opportunities are presented for growth and innovation in F&V food systems. The paper is organized into five sections based on primary points of intervention in global F&V systems: (1) research and development, (2) information needs to better inform policy & investment, (3) production (farmers, farming practices, and supply), (4) consumption (availability, access, and demand), and (5) sustainable & equitable F&V food systems and supply chains

Impact of green tea for colitis-associated colorectal cancer prevention in a multigenerational murine model incorporating the total Western diet.

Colorectal cancer (CRC) is the second leading cause of US cancer death, yet Americans routinely consume highly processed foods that are energy-dense and nutrient-poor, contributing to chronic inflammation. Other foods are known to contain bioactive molecules that protect against cancer by virtue of antioxidant properties. Over 27,000 research articles are published on green tea, a popular beverage, second worldwide only to water. Previous work has shown that green tea polyphenols decrease body fat composition, reverse insulin resistance, reduce cardiovascular disease risk, protect against pathogenic bacteria, improve brain function, increase lifespan, and suppress inflammatory processes that contribute to carcinogenesis. The objective of this project was to determine the efficacy of green tea extract (GTE) for CRC prevention after multigenerational exposure to standard or Western type diets. We hypothesized that GTE would reduce suppress development of inflammation-associated CRC in third-generation offspring, regardless of ancestral diet exposure. C57BL/6J mice were bred for three generations, during which they were fed a standard AIN93G diet or the total Western diet for rodents (TWD), during only the F0 generation, the F0 through F3 generations, or only the F3 generation. The AOM+DSS model of inflammation-associated CRC was employed in F3 offspring and mice were provided either plain drinking water or GTE supplementation. GTE decreased terminal body weight and relative fat mass in F3 females directly exposed to TWD compared to their counterpArts provided water. GTE consumption decreased tumor multiplicity and burden in both sexes after multi-generation exposure to TWD, as well as relative spleen mass in females (p=0.0083). GTE increased relative cecum mass (p=0.0113) in females after trans-generational TWD exposure. Preliminary analyses suggest that GTE supplementation reduced CRC severity only after cumulative TWD exposure over multiple generations

Impact of the Total Western Diet for Rodents on Colon Mucosal Gene Expression in a Multigenerational Murine Model of Colitis-Associated Colorectal Cancer

A Western type dietary pattern is a major risk factor for colitis-associated colorectal cancer (CAC). Observations from transgenerational studies suggest that epimutations may be inherited, resulting in persistent aberrant gene expression in offspring. Previously, our group reported that ancestral exposure to the total Western diet (TWD) increased CAC incidence and disease severity in F3 offspring. Moreover, exposure to TWD over multiple generations exacerbated disease in F3 offspring as compared to those fed TWD directly. For the present work, we hypothesized that ancestral or cumulative exposure to TWD will result in differential expression of cancer critical genes, explains the greater tumor abundance and burden observed in these mice. C57BL/6J mice were bred for three generations, during which they were fed a standard control diet (AIN93G) for all generations or TWD during only the F0 generation (ancestral), the F0 through F3 generations (multi-generation), or only the F3 generation (direct). The azoxymethane and dextran sodium sulfate (AOM+DSS) model of CAC was employed in F3 offspring, from which colon mucosa RNA was isolated and used for Illumina RNAseq with EdgeR for differential expression analysis. About 700 to 4500 differentially expressed genes (DEGs) were identified in colon mucosa from AOM&DSS initiated offspring, as compared to sham controls. For initiated mice, 119 DEGs were identified comparing cumulative TWD exposure to controls, and 36 differed from direct TWD fed animals. In sham mice, 101 DEGs were identified comparing direct to cumulative TWD exposed offspring; interestingly, these DEGs were associated with defense response, immune response, and response to interferon biological process ontology terms. Exposure to the TWD over multiple generations caused significant changes in genes involved in immune response in third generation offspring. Assessment of genome-wide patterns of promoter methylation is near completion and expected to reveal an epigenetic mechanism of action

Promotion of Colon Tumorigenesis in C57BL/6J Mice Following Multigenerational or Ancestral Exposure to the Total Western Diet and Intervention with Green Tea Extract

Colorectal cancer is the second leading cancer killer in the US and risk is on the rise for both middle aged and young adults. Although the Western dietary pattern is responsible for the majority of colorectal cancer incidence, Americans routinely consume highly processed foods that are rich in calories yet lacking essential nutrients. Many foods, like green tea, contain components that promote health and fight disease.Recent findings suggest that lifestyle factors, including nutrition, may also impact future generations of offspring and change the way genes function in our cells, without changes the genes themselves. We hypothesized that ancestral exposure to a Western diet would promote colorectal cancer in great-grand offspring that would be reversed by green tea extract supplementation and that these health outcomes would be reflected by the expression of genes related to cancer. To explore this, we fed mice a Western diet during all four generations (cumulative), only the fourth generation (direct), or only the first generation (transgenerational) and compared them to those that consumed a healthy control diet during all four generations. The fourth generation were provided either green tea extract or plain drinking water. Transgenerational Western diet exposure increased colorectal cancer occurrence and dysregulated a number of genes related to immune function and inflammation. This outcome was worsened by cumulative Western diet intake and occurred without affecting body weight or fat mass. Green tea extract reduced the number and size of tumors in all Western diet groups. This study is the first to investigate how diet induced transgenerational inheritance affects colorectal cancer outcome. Our findings suggest that we may be at the mercy of our ancestor’s dietary choices, however, dietary interventions with health promoting foods may provide protection against disease

Fermentation of Prebiotics in Whole Food Powders by Probiotic Bacteria Strains

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Modification of the gut microbiome offers potential for CRC prevention

Dietary supplementation with tart cherries for prevention of inflammation-associated colorectal cancer in mice

The cherry fruit is a nutrient-dense food that contains high amounts of anthocyanins. These bioactive food chemicals have anti-oxidant and anti-cancer properties that contribute to changes in cell signaling pathways involved in inflammation, carcinogenesis and angiogenesis. In this project, we aimed to determine whether dietary supplementation with tart cherries, prevents colon tumor development in mice consuming a Western diet compared to a prudent diet. We hypothesized dietary supplementation with freeze-dried whole tart cherries would suppress development of colon tumors in a model of colorectal cancer (CRC) incorporating the typical Western diet. A 2×2 factorial design was employed, whereby mice were fed either the standard AIN93G diet or the total Western diet (TWD), both with and without Montmorency tart cherry powder for a total anthocyanin content of 188 mg/kg diet. The azoxymethane and dextran sodium sulfate model of inflammation-associated CRC was employed. Supplementation with tart cherry powder caused a significant 40% reduction (