Source: COLORADO STATE UNIVERSITY submitted to
BENEFICIAL AND ADVERSE EFFECTS OF NATURAL, BIOACTIVE DIETARY CHEMICALS ON HUMAN HEALTH AND FOOD SAFETY
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
0212550
Grant No.
(N/A)
Project No.
COL00271B
Proposal No.
(N/A)
Multistate No.
W-2122
Program Code
(N/A)
Project Start Date
Oct 1, 2007
Project End Date
Sep 30, 2012
Grant Year
(N/A)
Project Director
Vivanco, J. M.
Recipient Organization
COLORADO STATE UNIVERSITY
(N/A)
FORT COLLINS,CO 80523
Performing Department
HORTICULTURE & LANDSCAPE ARCHITECTURE
Non Technical Summary
Plants contain a number of compounds that could be used as therapeutics. This project will search for biaoctive compounds in plants.
Animal Health Component
(N/A)
Research Effort Categories
Basic
26%
Applied
10%
Developmental
64%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
2060199100040%
2122420106030%
2132499107010%
3144010110320%
Goals / Objectives
1. Consumption of food-borne bioactive compounds can protect against human diseases such as cancer, inflammation, birth defects, and microbial infection. We will determine the mechanisms by which selected compounds exert their protective action. 2. Food-borne toxins and carcinogens are present per se or are induced by processing, preparation, and other post-harvest steps. We will identify mechanisms of action and develop biomarkers of natural and induced toxicants in food for human risk assessment and disease prevention. 3. Selected classes of bioactive compounds show potential for beneficial or adverse effects on human health. We will discover bioactive compounds that have beneficial or adverse effects on human health. 4. Modifying foods is an increasingly important strategy to improve nutrition and safety. Therefore, we will improve food safety by developing approaches to increase beneficial or decrease adverse effects of bioactive food constituents and microbial contaminants.
Project Methods
Our research will facilitate the identification and characterization of bioactive plant-derived compounds. We are targeting the following bioactivities antimicrobial, herbicidal and anticancer (tentative) activities. Furthermore, our research project will dissect the activity and effect of these plant-derived compounds at the biochemical and molecular levels.

Progress 10/01/07 to 09/30/12

Outputs
OUTPUTS: Researchers are conducting a clinical dietary intervention (called BENEFIT) in a colon cancer survivor population to assess the potential for bioactive rice bran and bean phytochemicals to increase the levels of beneficial microbes present in the gut microbial community resulting in modulation of mucosal immune responses and the increased the production of anti-tumerogenic and anti-inflammatory microbial metabolites such as butyrate and other short chain fatty acids (SCFAs). We have identified a target community of potentially harmful and beneficial microbes and are assessing how they may be altered by dietary rice bran or dry bean. These results are important because they could result in new dietary recommendations for colon cancer prevention and identify microbial and metabolite biomarkers that could be used to assess risk or evaluate responses to a particular intervention. We have also explored how the bioactivity of certain foods may be potentiated through microbial fermentation. Often anti-oxidant flavonoids and other bioactive chemicals are attached to plant cell wall matrices or are present as poorly absorbed glycosides. Fermentation of foods pre-consumption may enhance both the amount and bioavailability of these compounds by converting them to more easily absorbed aglycone forms or releasing them from ligno-cellulose matrices.We determined that Sacchromyces boulardii-fermentation of rice bran alters its phytochemical profile and increased cytotoxicity against Raji lymphoma cells and Caco-2 and HT-29 colon cancer cell lines. In vivo pharmacokinetics to study bioavailability of rice bran components are underway. Finally, we examined the bioactive components from a fermented Chinese tea that has shown cytotoxic effects against colon cancer cell lines HT-29 and CaCo-2 as well as antimicrobial activity against Staphylococcus aureus and Shigella sonnei. We have identified novel fatty acid amines that likely originate from the fermenting fungus and may contribute to this tea's bioactivity in vitro. We have also explored novel intestinal-mediated mechanisms of action for this tea. PARTICIPANTS: TIffany Weir, PhD; Brittany Barnett, Colorado State University undergraduate student TARGET AUDIENCES: The work described is targeted at the American population as a whole, although their are particular benefits to individuals suffering from chronic diseases such as cancer, diabetes, and obesity that could be derived from data obtained from the described projects. In addition, some of the findings, such as those related to rice bran and Salmonella could have global public health significance. PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
SUMMARY IMPACT. Bioactive chemicals naturally occur in foods, and can both help and harm human health. Over the 5 year span of this project, CSU participants advanced our understanding of the compounds that pose a risk to food safety and aid in disease-prevention. Understanding the complex relationship between dietary chemicals and human health remains a paramount concern to consumers, agricultural producers, food processors, health professionals, and policy makers charged with maintaining a safe and nutritious food supply. This critical information generated by CSU W2122 participants is passed on to consumers and others responsible for ensuring that Americans have a safe, healthy food supply.Impacts are summarized below as evidence of the project's contributions to society. 1. Fermentation of different rice bran varieties with the probiotic organism Saccharomyces boulardii altered the phytochemical profile of the rice bran to increased total phenolic compounds and enhance anti-proliferative properties in cancer cell lines. Fermentation could be a viable strategy for improving the nutritive and disease fighting properties of foods. 2. Dietary intervention with rice bran or dried bean decreased caloric intake, but increased total fiber consumption in healthy individuals and colon cancer survivors. The intervention resulted in promotion of specific intestinal bacteria considered to be beneficial to colon health (ie. butyrate producers) while decreasing the presence of amino acids and other compounds in fecal metabolotes associated with colorectal cancer (CRC) tumor occurence.This could result in new dietary strategies for colon chemoprevention. 3. Rice bran feeding of mice increased intestinal lactobacilli and decreased colonization when challenged with Salmonella. This could lead to new strategies to combat enteric pathogens and treat diarrheal diseases. 4. A fermented preparation of Chinese tea, fuzhuan tea, was found to improve insulin sensitivity, increase growth of intestinal Lactobacilli, and reduce liver stress in high fat diet fet rats. This tea offers potential therapeutic benefits for individuals suffering from non-alcoholic fatty liver disease, diabetes, and obesity.

Publications

  • Borresen EC, Henderson AJ, Kumar A, Weir TL, Ryan EP. 2012. Fermented foods: Patented approaches and formulations for nutritional supplementation and health promotion. Recent Patents on Food, Nutrition & Agriculture. 4: 134-140.
  • Xu X, Hu Y, Xiao W, Huang J, He X, Wu J, Ryan EP, Weir TL*. 2012. Effects of fermented Camilla sinensis, Fuzhuan tea, on egg cholesterol and production performance in laying hens. J. Int. Food and Agric. Res. 1:6-10.
  • Barnett BA and Weir TL*. 2012. Bacterial secretion. In: Secretions and Exudates in Biological Systems (eds. Baluska F, Vivanco JM). Springer, Berlin, Germany.
  • Kumar A, Henderson A, Forster GM, Chen MH, Goodyear AW, Bauer JE, Weir TL, Leach JE, Dow SW, Ryan EP (2012) Dietary Rice Bran Promotes Resistance to Salmonella Colonization and Mucosal Invasion in Mice. BMC Microbiology. 12, 71; http://www.biomedcentral.com/1471-2180/12/71
  • Weir TL*, Hu Y, Ryan EP, Lin W, Murray P, Fu D, Snook R, Xiao W. 2012. Medicinal teas: a review to summarize health benefits and highlight fermented tea. Herbalgram. 94: 45-49.
  • Fu D, Ryan EP, Huang J, Liu Z, Weir TL, Snook R, Ryan T. 2011. Fermented Camellia sinensis, Fuzhuan Tea, regulates hyperlipidemia and transcription factors involved in lipid catabolism. Food Research International 44: 2999-3005.
  • Manter DK, Weir TL, Vivanco JM. 2010. Sample pooling masks PCR-based estimates of soil microbial richness and community structure. Appl. Environ. Microbiol. 76, 2086-2090.
  • Weir TL, Stull VJ, Badri D, et al. 2008. Examination of global gene expression suggests an important role for nutrient acquisition in early pathogenesis in a Pseudomonas aeruginosa-plant infection model. Appl. Environ. Microbiol. 74: 5784-5791.
  • Weir TL*, Manter DM, Kofer W. 2011. Microbes: A new frontier in tropical chemical biology. In: Chemical Biology of the Tropics: An interdisciplinary approach. (eds. Vivanco JM, Weir TL). Springer, Berlin, Germany. Pp114.


Progress 01/01/11 to 12/31/11

Outputs
OUTPUTS: We have continued to determine the mechanisms of action by which food-borne bioactive compounds protect against human diseases such as cancer, inflammation, and microbial infection. We are currently conducting a clinical dietary intervention (called BENEFIT) in a colon cancer survivor population to assess the potential for bioactive rice bran and bean phytochemicals to alter the gut microbial community and increase production of antitumerogenic and antiinflammatory microbial metabolites such as butyrate. Additionally, we have measured outcomes that include changes in the target microbial population, detection of fecal SCFA as well as global metabolite profiling, serum levels of C-reactive protein, and fecal secretory IgA. A pilot dietary intervention in healthy adults has been completed. These studies will contribute to clinical intervention strategies for colon cancer prevention. We have also developed strategies to increase beneficial effects of bioactive food constituents. A potential mechanism by which polyphenols and other phytochemicals may be increased or made more bioavailable is through microbial fermentation. Often these chemicals are attached to plant cell wall matrices or are present as poorly absorbed glycosides. Fermentation pre-consumption may enhance both the amount and bioavailability of these compounds by converting them to more easily absorbed aglycone forms or releasing them from ligno-cellulose matrices. We have conducted studies to identify how Sacchromyces boulardii-fermentation of rice bran alters rice bran phytochemical content an in vitro activity against cancer cell viability (lymphoma, Caco, HT-29 cells). Studies are underway to determine if fermentation increases bioavailability by determining pharmacokinetics of bioactive phytochemicals present in plasma of rice bran (both fermented and non-fermented) fed canines. In addition to these studies, we are determining differences in the phytochemical profiles of a fermented Chinese tea (Fuzhuan tea) compared to green tea and its subsequent antimicrobial activity in both animal models (Salmonella-infected mice) and in vitro assays. PARTICIPANTS: Dr. Tiffany Weir, Department of Food Science and Human Nutrition, conducted the described studies in collaboration with Dr. Elizabeth Ryan from the Department of Clinical Sciences at Colorado State University and Chinese collaborators from Hunan Agricultural University in Changsha, Hunan Province China. Dr. Weir had the opportunity to share her findings related to this project at the annual W2122 meeting in Calistoga, CA in October 2011. TARGET AUDIENCES: Because we are examining interventions for improved health the target audience is the general public but with particular emphasis on those with colon cancer or at high risk for the disease, including obese individuals. PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
Determining the contribution of our microbial populations in the role of health and disease risk/development is a rapidly growing research area that may lead to more personalized medicine through novel and individualistic strategies prevent, identify, and treat chronic diseases. These studies contribute to this goal by identifying the impacts of specific dietary components on native microflora in a relevant human population and by identifying how microbial metabolism of plant-based foods can alter the bioavailability and activity of their beneficial chemicals. By examining the fecal microflora of healthy individuals and pre-surgical samples of colon cancer patients, we have identified "sentinel" microbial species that may play a role in the development of colon cancer or protection against it. These populations can then be used as benchmarks of responsiveness to dietary interventions or other types of treatments. Practical/Financial Impact: Rice bran is an agricultural by-product of rice production and determining its utility modulating the gut microbiota for potentially chemopreventive actions will provide a new market for rice producers, both in the US and in developing nations where rice production primarily occurs. In addition, it is a cheap and accessible strategy to modulate gut microflora which may have impacts on chronic diseases like gastrointestinal cancers that are prevalent in the developed world and on improving the immunity in developing world populations where diarrheal diseases and enteric pathogens occur more frequently.

Publications

  • Fu, D., Ryan, E.P., Huang, J., Liu, Z., Weir, T.L., Snook, R., Ryan, T. 2011. Fermented Camellia sinensis, Fuzhuan Tea, regulates hyperlipidemia and transcription factors involved in lipid catabolism. Food Research International. Doi: 10.1016/j.foodres.2011.07.008
  • Ryan, E.P., Heuberger, A.L., Weir, T.L., Barnett, B.A., Broeckling, C.D., Prenni, J.E. 2011. Rice bran fermented with Saccharomyces boulardii generates novel metabolite profiles with bioactivity. J Agric Food Chem. 59, 1862-1870.
  • Weir, T.L., et al. 2012. Medicinal Chinese Teas: A review summarizing their health benefits with focus of fermented tea. HerbalGram 93: 36-41.
  • Barnett, B. and Weir, T.L.* 2011. Bacterial secretions. In Secretions and Exudates in Biological Systems. (eds. Baluska and Vivanco) Springer, Berlin, Germany.


Progress 01/01/10 to 12/31/10

Outputs
OUTPUTS: We have continued with our studies to analyze the molecular mechanisms that roots utlize to exude phytochemicals. Additionally, we have conducted a series of greenhouse and field studies to determine the function of root exudates in the interactions between roots and the soil microbiome. Of particular importance was the realization that organic practices in potato cultivation have a positive effect on soil microbiome biodiversity and evenness as compared to intensive agricultural practices. The results of these studies will contribute to the development of sustainable agricultural practices. Finally, we have initiated a series of studies to analyze the proteome of the root exudates and to correlate the secretion of these macromolecules with plant development. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Participated in forums with major agricultural companies to develop products for commercial agriculture related to our studies.

Publications

  • De-la-Pena C, Vivanco JM (2010) Root-microbe interactions: the importance of protein secretion. Current Proteomics 7:265-274
  • De-la-Pena C, Lei Z, Watson BS, Badri DV, Brandao MM, Silva-Filho MC, Sumner LW, Vivanco JM (2010) Root secretion of defense-related proteins is development-dependent and correlated with flowering time. Journal of Biological Chemistry 285:30654-30665
  • Sugiyama A, Vivanco JM, Jayanty SS, Manter DK (2010). Pyrosequencing assessment of soil microbial communities in organic and conventional potato farms. Plant Disease 94:1329-1335
  • Broz AK, Broeckling CD, De-la-Peaa C, Lewis MR, Greene E, Callaway RM, Sumner LW, Vivanco JM (2010) Plant neighbor identity influences plant biochemistry and physiology related to defense. BMC Plant Biology 10:115 http://www.biomedcentral.com/1471-2229/10/115
  • Manter DK, Weir TL, Vivanco JM (2010) Negative effects of sample pooling on PCR-based estimates of soil microbial richness and community structure. Applied and Environmental Microbiology 76:2086-2090
  • Badri DV, Loyola-Vargas VM, Broeckling CD, Vivanco JM (2010) Root secretion of phytochemicals in Arabidopsis is predominantly not influenced by diurnal rhythms. Molecular Plant 3: 491-498
  • Mantilla MA, Ramos JL, Bakker PAHM, Doornbos R, Badri DV, Vivanco JM, Ramos-Gonzalez MI (2010) Pseudomonas putida KT2440 causes induced systemic resistance and changes in Arabidopsis root exudation. Environmental Microbiology Reports 2:381-388


Progress 01/01/09 to 12/31/09

Outputs
OUTPUTS: Whether plants can influence and take advantage of the surrounding community of organisms has been debated for years. Evidence published to date suggesting that plants manipulate the soil microbial communities has been largely correlative, but a clear-cut mechanism used by plants to accomplish and benefit from this manipulation of microbial communities is lacking in the literature. Our laboratory has recently achieved results that allow us to make some generalizations about the plant-soil microbial community interaction. For example, we have found that the ratio of phenolics vs. sugars in the root exudates of Arabidopsis had a profound effect on soil microbial composition. Specifically, we have determined that ABC (ATP Binding Cassette) transporters are involved in root secretion and that a mutant lacking the AtPDR2 transporter elicits dramatic quantitative and qualitative changes in Arabidopsis native soil microbial communities. These changes are correlated with an increase in phenolic compounds and a decline in sugars in the root exudates of the mutant compared to the wild type (wt) and several other ABC transporter mutants. Interestingly, exudates from Atpdr2 cultivated a microbial community with a relatively greater abundance of potentially beneficial bacteria (i.e., plant growth promoting rhizobacteria-PGPRs, nitrogen fixers); and were specifically enriched in bacteria involved in heavy metal remediation. We have continued with our studies in collaboration with Dr. Pagliassoti to determine the mechanism by which the root exudates of specific varieties of onion reduce lipid accumulation in rats. Additionally, there is an on-going collaboration with Dr. Douglass Thamm to screen root exudates of various plants for anticancer activity; the results of those studies are currently being analyzed. Finally, new studies are being initiated to analyze the content of reseveratrol in several varieties of grapes grown in Colorado. PARTICIPANTS: Not relevant to this project. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
An invention disclosure was filed on the Atpdr2 gene mutation.

Publications

  • Badri DV, Weir TL, van der Lelie D, Vivanco JM (2009) Rhizosphere chemical dialogues: plant-microbe interactions. Current Opinion in Biotechnology 20:642-650
  • Badri DV, Quintana N, El Kassis EG, Kim HK, Choi YH, Sugiyama A, Verpoorte R, Martinoia E, Manter DK, Vivanco JM (2009) An ABC transporter mutation alters root exudation of phytochemicals that provokes an overhaul of natural soil microbiota. Plant Physiology 151:2006-2017.
  • Mantilla MA, Ramos JL, Bakker PAHM, Doornbos R, Badri DV, Vivanco JM, Ramos-Gonzalez MI (2009) Pseudomonas putida KT2440 causes induced systemic resistance and changes in Arabidopsis root exudation. Environmental Microbiology Reports (in press; doi: 10.1111/j.1758-2229.2009.00091.x)
  • Broz AK, Vivanco JM (2009) The genomics of plant invasion: a case study in Spotted knapweed. In Weedy and Invasive Plant Genomics. Stewart CN eds. Wiley-Blackwell Press. Hoboken, NJ. pp. 177-197
  • Kaplan F, Badri DV, Zachariah C, Srinivasan J, Adjerdini R, Sandoval FJ, Rojae S, Levine LH, Zhang F, Robinette SL, Alborn HT, Zhao W, Stadler M, Nimalendran R, Dossey AT, Brushweiler R, Vivanco JM, Edison AS. (2009) Bacterial attraction and quorum sensing inhibition in Caenorhabditis elegans exudates. Journal of Chemical Ecology 35(8): 878-92
  • Badri, D., and Vivanco, J.M. (2009) Regulation and function of root exudates. Plant, Cell and the Environment 32:666-681
  • Simoes, K., Du, J., Pessoni, R.A.B., Cardoso-Lopes, E.M., Vivanco, J.M., Stermitz, F.R., and Braga, M.R. (2009) Ipomopsin and hymenain, two biscoumarins from seeds of Hymenaea courbaril. Phytochemistry Letters 2: 59-62
  • Broz, A.K., Manter, D.K., Bowman, G. Muller-Scharer, H., Vivanco, J.M. (2009) Plant origin and ploidy influence gene expression and life cycle characteristics in an invasive weed. BMC Plant Biology 9:33 doi:10.1186/1471-2229-9-33
  • Quintana, N., El Kassis, E.G., Stermitz, F.R., and Vivanco, J.M. (2009) Phytotoxic compounds from roots of Centaurea diffusa Lam. Plant Signaling and Behavior 4:66-71


Progress 01/01/08 to 12/31/08

Outputs
OUTPUTS: We have continued with our studies to determine the molecular mechanisms that roots utlize to exude phytochemicals, and studied the function of root exudates in the interactions between roots and soil microbes. Also, we have started two studies to determine the potential of root exudates as therapeutics. The first study in collaboration with Dr. Michael Pagliassotti (Food Science and Human Nutrition) analyzed a battery of root exudates from several plants for lipid reducing properties. We found that a root exudate, derived from onion, has strong biological activity. This exudate has been shown to normalize the glycemic index and lipid profile in obese diabetic rats, and is covered under CSU invention disclosure 08-018: "Plants as a Source of Bioactive Molecules for the Treatment of Obesity and Type 2 Diabetes". Interestingly, it has been found that bioactivity is restricted to certain varieties of onions. In the second project, we have partnered with Dr. Douglass Thamm (Clinical Sciences) to study if root exudates from a variety of plants have anticancer activites. Dr. Thamm has a battery of cancer cells and atincacer assays available in his laboratory. These two studies will provide information about the potential of root exudates as therapeutics. PARTICIPANTS: Not relevant to this project. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
- An invention disclosure was filed on some of these findings as detailed above.

Publications

  • 1. De-la-Pena, C., Lei, Z., Watson, B., Sumner, L.W., and Vivanco, J.M. (2008) Root microbe communication through protein secretion. Journal of Biological Chemistry 283:25247-25255 2. Weir, T.L., Stull, V.J., Badri, D., Truck, L.A., Schweizer, H.P., and Vivanco, J.M. (2008) Global gene expression profiles suggest an important role for nutrient acquisition in early pathogenesis in a plant model of Pseudomonas aeruginosa infection. Applied and Environmental Microbiology 74:5784-5791
  • 3. Badri, D.V., Loyola-Vargas, V.M., Du, J., Stermitz, F.R., Broeckling, C.D., Iglesias-Andreu, L., and Vivanco, J.M. (2008) Transcriptome analysis of Arabidopsis roots treated with signalling compounds: a focus on signal transduction, metabolic regulation and secretion. New Phytologist 179:209-223
  • 4. Badri, D.V., Loyola-Vargas, V.M., Broeckling, C.D., De-la-Pena, C., Jasinski, M., Santelia, D., Martinoia, E., Sumner, L.W., Banta, L.M., Stermitz, F., and Vivanco, J.M. (2008) Altered profile of secondary metabolites in the root exudates of Arabidopsis ATP-Binding Cassette (ABC) transporter mutants. Plant Physiology 146:762-771
  • 5. Broeckling, C.D., Broz, A.K., Bergelson, J., Manter, D.K., Vivanco, J.M. (2008) Root exudates regulate soil fungal community composition and diversity. Applied and Environmental Microbiology 74 738-744