Browsing by Author "Ryan, Elizabeth P., advisor"

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A comprehensive analysis of rice bran as a functional food for global health
(Colorado State University. Libraries, 2024) Weber, Annika Marie, author; Weir, Tiffany L., advisor; Ryan, Elizabeth P., advisor; Bunning, Marisa, committee member; Vilander, Allison, committee member; Conant, Richard, committee member
Global nutrition security and public health improvement rely on diverse diets, with whole grains playing a key role in meeting these challenges. Rice, a staple grain for over half the world's population, is typically consumed in its refined form, which involves removing the bran layer. This bran layer, however, is a rich source of fiber, essential fatty acids, amino acids, vitamins, minerals, and phytochemicals, which are key components that contribute to the health benefits of whole grains. The nutrient properties of rice bran and its demonstrated ability to protect against gastrointestinal diseases make it a promising addition to public health initiatives. To fully harness these benefits, a comprehensive analysis of rice bran's health potential and strategies for incorporation into global nutrition is necessary. The purpose of this dissertation was to explore the role of rice bran in enhancing gut health, particularly in colorectal cancer (CRC) prevention and malnutrition treatment, as well as provide considerations for food safety and an assessment of community preparedness for public health interventions. Here, the metabolism of rice bran by the gut microbiota and subsequent generation of metabolites related to CRC protection in a murine model and CRC survivors is evaluated. Additionally, methods to reduce arsenic levels in rice bran are explored, and an assessment is presented of community readiness for dietary interventions, which are challenges to overcome in preparing rice bran for public health. The use of rice bran to enhance nutrient density in malnutrition treatment foods is also explored, with a detailed protocol of the Solutions to Enhance Health using Alternative Treatments (SEHAT) clinical trial. Anthropometric outcomes from the SEHAT study are then analyzed to assess the impact of rice bran on childhood growth and malnutrition recovery. The diverse health benefits of rice bran, from cancer prevention to malnutrition treatment, are demonstrated here. In providing evidence for its safety, efficacy, and potential for global use, the research underscores the viability of rice bran as a functional food in clinical and public health guidelines. These studies contribute to the broader efforts of leveraging rice bran for improved global nutrition and community health.
Open Access
A metabolomics approach for examining synbiotic protection against infectious enteric pathogens
(Colorado State University. Libraries, 2019) Nealon, Nora Jean, author; Ryan, Elizabeth P., advisor; Dean, Gregg, committee member; Henry, Charles, committee member; Tobet, Stuart, committee member
Infectious gastrointestinal diseases contribute to billions of global cases of human illness annually. Salmonella enterica serovar Typhimurium and human rotavirus represent two human health challenges, where escalating multidrug resistance and poor vaccine efficacy warrant the development of alternative treatments. Health-promoting probiotic microorganisms are becoming increasingly studied for their production of bioactive small molecules that confer protective effects against enteric pathogens. Among probiotics, Lactobacilli, Bifidobacteria and E. coli Nissle form synbiotics with rice bran, the prebiotic-rich outer coating of brown rice, to enhance animal protection against S. Typhimurium infection and human rotavirus diarrhea compared to probiotics or rice bran alone. Despite these beneficial interactions of probiotics and rice bran, a knowledge gap exists in our understanding of the synbiotic small molecules driving these protective effects, especially across probiotic species differences in small molecule production. To test our overarching hypothesis that probiotic species would metabolize rice bran into distinct suites of small molecules that suppressed pathogen function, we first applied the cell-free supernatant from L. paracasei, L. fermentum, and L. rhamnosus cultured with rice bran to S. Typhimurium and observed magnitude-dependent growth suppression across synbiotics. Both L. paracasei and L. fermentum supernatants exhibited enhanced growth suppression compared to their probiotic-only treatments and contained differentially abundant antimicrobial lipids, amino acids, and nucleotides that have not been previously characterized for antimicrobial functions. The cell-free supernatant of the L. paracasei and L. fermentum synbiotics were fractionated and applied to S. Typhimurium to identify the small molecules driving their enhanced Salmonella growth suppression. Metabolite profiles were also compared across synbiotics. Each synbiotic produced several bioactive fractions that suppressed Salmonella growth. While both L. fermentum and L. paracasei bioactive fractions contained abundant lipids, L. fermentum fractions were selectively-enriched in the energy metabolite fumarate and L. paracasei fractions were uniquely-enriched with amino acids (imidazole lactate, ornithine) suggesting that Lactobacillus spp. probiotics could differentially metabolize rice bran to drive Salmonella growth suppression with different suites of small molecules. To examine probiotic metabolism of rice bran in mammalian systems, we compared the intestinal and blood metabolomes of healthy adult mice and gnotobiotic, neonatal pigs that were fed combinations of probiotics and rice bran to the metabolomes of animals consuming rice bran or probiotics alone. In mice, a notable difference following 15 weeks consumption of B. longum fermented was that the arginine metabolite N-delta-acetylornithine was significantly increased in B. longum fermented rice bran compared to rice bran alone and was elevated in both the colon tissue and blood of mice consuming fermented rice bran compared to rice bran alone. In gnotobiotic neonatal pigs, three weeks of prophylactic supplementation with E. coli Nissle and L. rhamnosus GG and rice bran were more effective at reducing human rotavirus diarrhea compared to pigs given these probiotics or rice bran alone. Approximately 300 colon and blood metabolites that were differentially-abundant between synbiotic-consuming pigs versus pigs consuming probiotics alone were identified, over 50% of which were lipids and amino acids. Similar modulations lipid and amino acid metabolites (sphingolipids, diacylglycerols, arginine metabolites) were identified in the colon tissue and blood of mice and pigs consuming the synbiotic treatments. Consequently, the association of these metabolite profiles with human rotavirus diarrhea protection, when combined with their presence in two mammalian models, provides strong rationale for these infectious enteric disease protective roles harbored by these metabolites. The results of these studies provide a role for synbiotics in the prevention of infectious gastrointestinal diseases. For the first time, high-throughput metabolomics analyses were applied to identify differential bioactive metabolite production by Lactobacillus spp. + rice bran synbiotics that suppressed S. Typhimurium growth, as well as to compare bioactive metabolites produced by B. longum, L. rhamnosus GG, and E. coli Nissle in mice and pigs that were protective against human rotavirus diarrhea. The contributions of amino acids and lipids to the enhanced capacities of these synbiotics compared to probiotics or rice bran alone can be studied further for their mechanisms of action on pathogens. Ultimately, these bioactive synbiotic metabolites can guide the optimization and development of broad-spectrum antimicrobials and other prophylactic agents that protect against infectious enteric diseases across the human and animal lifespan.
Open Access
Dietary modulation of canine metabolism for obesity management and cancer risk reduction
(Colorado State University. Libraries, 2015) Forster, Genevieve Michele, author; Ryan, Elizabeth P., advisor; Page, Rodney L., committee member; Bauer, John E., committee member; Avery, Anne C., committee member
Metabolic aberrancies associated with environmental exposures and excess adiposity can increase risk for multiple chronic diseases. Obesity is the primary nutritional disorder of companion dogs and incidence and prevalence rates continue to increase, yet little is known about underlying metabolic disruption in obese dogs or the role of environmental contaminants to which companion dogs are exposed. Cooked common beans (Phaseolus vulgaris, L.) are a rich source of macro-, micro-, and phytonutrients that have potential to support healthy weight management in dogs, modulate metabolism, and decrease risk for chronic disease, but have yet to be evaluated for safety and digestibility in dogs. Given the prevalence of obesity in companion dogs and the potential of bean consumption to improve health, the overarching hypothesis for this dissertation is that cooked beans are well tolerated and palatable in dog food and beneficially modulate underlying metabolic pathways associated with canine obesity and environmental exposures. The major objectives in this dissertation were to 1) determine environmental exposures and obesity associated metabolic aberrancies in companion dogs; 2) investigate the feasibility, safety and digestibility of incorporating cooked bean powders into nutritionally complete dog food formulations; and 3) determine the effects of weight loss and bean intake on metabolic parameters. To accomplish these objectives, 66 clinically healthy, adult companion dogs of various breeds and genders were recruited to participate in randomized, controlled bean-based dietary intervention studies performed at Colorado State University Veterinary Teaching Hospital and Wellington Animal Hospital. The specific hypotheses tested were: • Companion dogs are exposed to detectable levels of environmental pollutants and exhibit altered metabolomes associated with obesity. • Dry dog foods formulated with 25 % weight/weight cooked bean powders are safe, digestible, and well tolerated compared to a nutrient matched control diet. • Dogs consuming bean-based diets will have altered lipid and carbohydrate metabolism, reduced inflammation, increased expression of satiety gut hormones, and decreased insulin resistance. We first determined the background exposures to pesticides as detected in urine from 21 normal weight dogs. Urine samples collected from the dogs were screened for a panel of 301 pesticides using an established ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) platform. Fifteen distinct pesticides were detected: the most frequently detected compounds in canine urine were atrazine, fuberidazole, imidacloprid, terbumeton, and clopyralid. We next evaluated 66 clinically healthy dogs that were normal weight, overweight, or obese for differences in serum biochemistry, microbiome, and metabolome. The proportion of overweight and obese dogs with hemolysis, creatinine kinase, and aspartate aminotransferase (AST) levels outside reference ranges was higher than normal weight dogs. Levels of AST, chloride, and gamma-glutamyl transpeptidase were lower in overweight or obese dogs. The fecal microbiomes were evaluated in a subset of 50 dogs using 16S Illumina based sequencing. The fecal microbiome comprised, in order of abundance, the phyla Firmicutes, Bateroidetes, Proteobacteria, and Actinobacteria. Significant variation existed between all dogs with no differences found at the level of phyla, class, order, family, or genus level. The fecal, plasma, and urine metabolome of 66 dogs were evaluated by liquid chromatography (LC) and gas chromatography coupled to mass spectrometry (MS), and 266 compounds were differentially expressed by weight phenotype. Difference in plasma metabolites accounted for 44 % of the variation between normal weight, overweight, and obese dogs. To determine the safety and digestibility of incorporating cooked bean powders into nutritionally complete dog foods, three clinical trials were carried out. Dogs consuming bean-based diets maintained indices of adequate nutritional intake as mandated by the Association of American Feed Control Officials (AAFCO) feeding trials. Bean-based diets were as digestible as the matched, standard ingredient, control (CON) dog foods. In overweight dogs undergoing weight loss, the black bean (BB) diet had higher total dry matter and crude protein digestibility and both the navy bean (NB) and black bean diets had higher carbohydrate digestibility than the CON diet. No increased flatulence or major change in fecal consistency was reported by any of the owners for any dogs. Normal weight dogs consuming beans had lower serum cholesterol levels than the CON dogs, and dogs undergoing weight loss on bean-based diets had decreases in serum HDL, LDL, and triglycerides. Metabolites associated with lipid, carbohydrate, and protein metabolism were altered in bean consuming dogs; however in dogs undergoing weight loss, the greatest shift in the metabolome was observed in response to weight loss, independent of diet. This work highlights the utility of metabolomic platforms for evaluating the metabolism of dogs and determining intervention responsive metabolic pathways. These data provide a foundation for continued investigation into the role of beans for healthy weight management and obesity and cancer prevention in dogs.
Open Access
Investigation of dietary rice bran for protection against Salmonella enterica Typhimurium infection in mice
(Colorado State University. Libraries, 2014) Kumar, Ajay, author; Ryan, Elizabeth P., advisor; Dow, Steven, committee member; Leach, Jan, committee member; Schenkel, Alan, committee member; Weir, Tiffany, committee member
Rice bran is a byproduct of rice milling for white rice. Rice bran is a rich source of nutrients such as vitamins, minerals, soluble and insoluble fibers, fatty acids, polyphenols and proteins. Research has shown the beneficial health effects of rice bran in hyperlipidemia, diabetes, immune modulation, allergies and cancer. This dissertation focuses on evaluation of rice bran for protection against Salmonella using a mouse model of oral infection. Salmonella is a food and water borne pathogen that affects a variety of hosts including plants, animals and humans. Salmonella infections are a major public health challenge around the globe. Currently, salmonellosis is treated using high doses of synthetic antimicrobials and the problem of drug resistance has increased. In this scenario, alternative and sustainable interventions are needed to control Salmonella infections. Several dietary agents have been studied for protective effects in Salmonella infection models. We tested the prophylactic effects of dietary rice bran in a Salmonella model of infection using female 129S6/SvEvTac mouse model with infection of Salmonella enterica Typhimurium 14028s strain. Feeding of 10% dietary rice bran for one week prior to infection significantly (p<0.05) reduced fecal excretion of Salmonella in orally infected mice. Salmonella-infected, rice bran fed mice also showed a significant decrease in systemic inflammatory cytokines such as TNF-α, IFN-γ and IL-12 as compared to control diet fed animals. The colonization resistance against enteric pathogens is highly influenced by composition of gut microflora. Supplementation of dietary rice bran increased the number of Lactobacillus spp. in feces of mice as compared to mice that were fed control diet. Research has shown that oral administration of some species of Lactobacillus reduces the colonization of Salmonella. We hypothesized that rice bran components also enhance mucosal protection by preventing Salmonella entry into the epithelial cells. Methanolic rice bran extracts were assessed in mouse small intestinal epithelial (MSIE) cells for blocking Salmonella entry and intracellular replication. Rice bran extract significantly reduced Salmonella entry and intracellular replication into MSIE cells. These results suggest the potential mechanisms for dietary rice bran induced improvement of colonization resistance against Salmonella. Given that rice crops have a large variation in genotype and phenotype such as in yield, disease and pest resistance, drought resistance, and nutrient quality, we hypothesized that variation in rice bran across cultivars induces differential protection against Salmonella infection due to differences in their phytochemical profile. A panel of six varieties namely IAC 600, Jasmine 85, IL 121-1-1, Wells, Red Wells and SHU 121 were tested in the in vitro and in vivo model of Salmonella infection. We found that rice bran extracts across varieties inhibited Salmonella entry into the MSIE and Caco-2 cells to different extents. IAC 600 fed animals significantly (p<0.05) reduced Salmonella fecal excretion as compared to the control diet fed animals. IAC 600 fed animals also reduced Salmonella fecal shedding significantly (p<0.05) as compared to SHU 121 diet fed animals at 2 and 6 days post Salmonella infection. Histopathological analysis revealed that IAC 600 diet fed animals had better ileal pathological scores as compared to SHU 121 and the control diet fed animals post Salmonella infection. SHU 121 and the control diet fed groups showed higher ulceration and inflammatory changes in ileum as compared to IAC 600 fed animals. Next we analyzed the fatty acid profile, mineral profile and total phenolic contents of rice bran. Stearic acid, lignoceric acid, boron and total phenol content were significantly correlated with Salmonella fecal shedding in mice across varieties. However, further studies are required to confirm the role of these nutrients from rice bran in protection against Salmonella. These results suggest that the variety of rice plays an important role in bran-induced protection against Salmonella infection and this difference in protection across the varieties could be attributed to a combination of bioactive components. Our studies suggest that dietary rice bran improves colonization resistance against Salmonella in mice. Rice bran could have important role in prevention of enteric infections in resource scarce populations and further human clinical studies are required. Rice bran may also be evaluated for supplementing diets of food animals to prevent Salmonella infections and therefore could have a potential role in food safety.
Open Access
Relationships between objectively measured physical activity and stool metabolome in individuals at high risk for colorectal cancer
(Colorado State University. Libraries, 2019) Beale, Melanie N., author; Leach, Heather J., advisor; Ryan, Elizabeth P., advisor; Hickey, Matthew S., committee member; Melby, Chris L., committee member
Physical activity is known to reduce the risk of colorectal cancer and adenomatous polyp recurrence. Targeted metabolomic profiling of the stool metabolome may provide insight to the mechanistic links between physical activity and colorectal cancer. This study utilized baseline physical activity and metabolomics data from a dietary fiber intervention for individuals at high risk for colorectal cancer. Participants (N=21), 59+/-9 years, BMI 28.1+/-3.35 wore an activPAL™ accelerometer for 7 consecutive days, provided a stool sample, and a 3-day dietary log. Stool bile acids and short chain fatty acids were quantified with gas chromatography mass spectroscopy and ultra-high performance liquid-chromatography tandem mass spectrometry. Linear regression models examined relationships between light intensity physical activity minutes, moderate to vigorous physical activity minutes, MET-hours per day, and sedentary minutes, with abundances of short chain fatty acids and bile acids while accounting for dietary fiber intake. Light intensity PA minutes predicted butyrate and propionate abundance when accounting for dietary fiber. MVPA predicted deoxycholic acid and ursodeoxycholic acid abundance. These data suggest that both low intensity PA and MVPA may both have implications for colorectal cancer primary and secondary prevention through different mechanisms.
Open Access
Relationships between plasma cytokines, leukocyte telomere length, serum lipid profile, and nutrient intake in healthy adults following a 4-week dietary intervention study
(Colorado State University. Libraries, 2016) Harbison, Gregory James, author; Ryan, Elizabeth P., advisor; Bailey, Susan M., committee member; Tjalkens, Ronald B., committee member; Weir, Tiffany L., committee member
Colorectal cancer is the third most commonly diagnosed cancer worldwide and the fourth leading cause of cancer-related death. The etiology of colorectal cancer is predominately attributed to modifiable lifestyle factors that promote chronic inflammation, and only 20% of colorectal cases are credited to hereditary syndromes. Specifically, recent nutritional studies have suggested that diet modification is a promising lifestyle intervention for reducing systemic inflammation and promoting colorectal cancer prevention and remission. In particular, rice and navy beans have been identified as two foods with anti-inflammatory and anti-neoplastic properties that warrant evaluation for chemoprevention through dietary supplementation in humans. In this study, plasma cytokines (IL-2, IL-4, IL-6, IL-8, IL-10, TNF, and VEGF) and leukocyte telomere length were measured at baseline, two weeks, and four weeks in individuals with and without a history of colorectal cancer who consumed a diet supplemented with rice bran, navy beans, or a placebo-control for 28 days. Serum lipid profile and nutrient intake were also measured. At baseline, the three diet intervention groups had no significant differences in cytokine concentration, telomere length, or lipid profile. At the end of the study, individuals with a history of colorectal cancer who consumed the navy bean supplemented diet had significantly higher plasma TNF and VEGF concentrations than individuals consuming the control diet. Otherwise, at the end of the study, no significant differences in cytokine concentration or telomere length between groups existed. Additionally, compared to males, females with a history of colorectal cancer had significantly longer telomeres at baseline but not at four weeks. Females with a history of colorectal cancer also had significantly lower IL-4, IL-6, and IL-10 at baseline, but no significant difference was found at four weeks. Linear correlation analysis on repeated measures that adjusted for sex, age, and total energy intake showed significant correlations between several study variables. Telomere length was inversely correlated with age, serum triglyceride level, carbohydrate intake, and saturated fat intake. IL-2 and IL-4 concentrations were inversely correlated with α-Tocopherol intake. IL-8 was inversely correlated with vitamin B3 intake. VEGF was positively correlated with vitamin B9 intake. Total serum cholesterol was positively correlated with saturated fat intake and inversely correlated with β-Carotene intake. Serum LDL was inversely correlated with β-Carotene intake, and serum HDL was positively correlated with intake of saturated fat and linolenic acid. Triglyceride level was inversely correlated with intake of β-Carotene and fiber and was positively correlated with selenium intake. Finally, comparison of two experimental methods for telomere length measurement showed positive but inconclusive correlations.