Source: UNIVERSITY OF CALIFORNIA, DAVIS submitted to NRP
BENEFICIAL AND ADVERSE EFFECTS OF NATURAL CHEMICALS ON HUMAN HEALTH AND FOOD SAFETY
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
1015545
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
W-4122
Project Start Date
Feb 1, 2018
Project End Date
Sep 30, 2022
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
UNIVERSITY OF CALIFORNIA, DAVIS
410 MRAK HALL
DAVIS,CA 95616-8671
Performing Department
Food Science and Technology
Non Technical Summary
An essential component to harnessing the bioactive properties of foods and beverages is a mechanistic understanding of the human intestinal microbiota. The intestinal microbiota perform an untold number of functions that modulate host physiology. These activities are intimately tied to the human the diet which provides the substrates for microbial growth and competition. To detangle the complex web of microorganisms in the human gut, this project seeks to investigate known beneficial (probiotic) bacterial residents of the digestive tract. Using existing molecular genetic methods to investigate model strains and emerging technologies to study the breadth and depth of the microbiome (e.g. HTP DNA sequencing), the project will result an improved understanding of how known microbial metabolites (e.g. short chain fatty acids) and novel, newly discovered microbial compounds (e.g. secreted proteins), are sensed by epithelial and immune cells in the intestine to result in signaling cascades at other distal sites in the body.
Animal Health Component
25%
Research Effort Categories
Basic
50%
Applied
25%
Developmental
25%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
70240991040100%
Goals / Objectives
Examine the effects of phytochemicals and other dietary components on gut microbiota and intestinal function.
Project Methods
UCD will examine how dietary probiotic bacteria and specific (probiotic) members of the indigenous intestinal microbiome can benefit health via modulation of the intestinal epithelium. Studies will focus on the specific effector compounds made by these bacteria that prevent epithelial barrier dysfunction. In particular, we are interested in elucidating the precise host-microbe signaling pathways that result in systemic physiologic changes. These investigations will be informed by the use of HTP DNA sequencing methods, intestinal modulation by the introduction of fermentable fibers into the diet, and encompassed in clinical trials and in animal and in vitro models.

Progress 10/01/19 to 09/30/20

Outputs
Target Audience:Dietary bioactive chemicals are defined in this proposal as naturally occurring substances produced by plants or microbes that exert beneficial or undesirable effects when they are consumed or produced by human or microbial metabolism in the body. How these chemicals influence human health, disease development, and food safety is important to everyone. Understanding how to enhance the benefits or minimize the risks of specific dietary compounds is important for agricultural producers, food processors, healthcare professionals, and policy makers charged with determining optimal human nutrition requirements and maintaining the safety of the food supply. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?This project has provided training to visiting scholars, Postdoctoral Fellows, PhD students, technicians, and undergraduate student interns. The individuals on the project received training from Dr. Marco on probiotic bacteria, fermented foods, fermentable fibers/prebiotics, gut microbiology, and mechanisms of intestinal inflammation and diet-induced obesity. These individuals are responsible for conducting animal and bacteriology experiments well as analyzing results in cooperation with Dr. Marco. How have the results been disseminated to communities of interest?Dissemination events include conference presentations, published journal articles, and consultations with local and international food processors and members of the media. Dissemination of knowledge beyond a scientific audience has included on-site tours of the research laboratory and description of the research program to university students, international visitors, casual visitors to the university (members of the public) and stakeholders (representing industrial sectors related to food science, nutrition, and health). What do you plan to do during the next reporting period to accomplish the goals?Activities for the next reporting period encompass the further development of objective 1 to achieve the goals of the project. Specifically in Objective 1 we are examining the effects of phytochemicals and other dietary components on the gut microbiota and intestinal function. We will perform metagenome DNA sequencing to identify the functional genes present in intestinal contents. We will also perform gene knockout and overexpression studies to elucidate the specific mechanisms of beneficial bacteria function in the intestine.

Impacts
What was accomplished under these goals? Progress this year was made for investigations on health-benefiting effects of fermented foods and probiotic bacteria. Specifically, we investigated how proteins and metabolites made by Lactiplantibacillus (Lactobacillus) plantarum contained in fresh, fermented fruits and vegetables and ingested as probiotics can stimulate intestinal epithelial cell repair. These studies took the form of tests of cells and metabolites on human intestinal cells in vitro in the laboratory and by the study of the cellular, genetic, and biochemical basis for the outcomes. One particular emphasis was on a specific anti-bacterial (bacteriocin) made by L. plantarum in foods and the digestive tract. We showed that this bacteriocin changes intracellular metal homeostasis in sensitive bacterial cells as well as the intestinal epithelium. In a different vein of the research, we pursued studies to understand how L. plantarum can reduce its extracellular environment through extracellular electron transport pathways. This activity is important in the production of fermented foods and may be useful for modifying the intestinal environment to reduce oxidative stress. Outputs of these studies included peer-reviewed publications, presentations, and the completion of a PhD thesis on the diversity of lactic acid bacteria on plants, including agricultural crops. We also continued our investigations to elucidate how resistant starch type 2 (RS2) and other dietary fibers, including whole grains (WG), may reduce the risk for obesity and type 2 diabetes as a consequence of stimulating (and minimizing) growth of certain bacteria in the large intestine. This work included metataxonomic and metatranscriptomic analysis of intestinal microbiota in response to RS2 and WG diet consumption in the presence of moderate or high levels of fat intake. The findings showed that refined, high-amylose maize high in RS2 results in much greater changes to the intestinal ecosystem than WG, regardless of dietary fat consumed. Besides leading to taxonomic changes, RS2 conferred increased expression of microbial genes specific for starch breakdown as well as genes required for protein folding and stability, possibly due to reductions in lumenal pH. Combining RS2 and WG in the same diet resulted in intermediate rather than additive effects of either diet alone. These findings together with the observed changes in intestinal metabolites (short chain fatty acids) show that future studies may lead to the fine-tuning of dietary fiber composition so that it is more useful for targeting selected bacterial taxa in the intestine that may be needed to achieve a specific and intended health outcome.

Publications

  • Type: Journal Articles Status: Published Year Published: 2020 Citation: Zachary A. Bendiks, Knud E.B. Knudsen, Michael J. Keenan, and Maria L. Marco. 2020. Conserved and variable responses of the gut microbiome to resistant starch type 2. Nutrition Research. 77:12-28. doi: 10.1016/j.nutres.2020.02.009
  • Type: Journal Articles Status: Published Year Published: 2020 Citation: Derrick Risner, Maria L. Marco, Sara A. Pace, and Edward S. Spang. 2020. The potential production of the bioactive compound pinene using whey permeate. Processes. 8(3), 263; https://doi.org/10.3390/pr8030263
  • Type: Journal Articles Status: Published Year Published: 2020 Citation: . Riley L. Hughes, Mary E. Kable, Maria L. Marco, Nancy L. Keim, 2019. The role of the gut microbiome in predicting response to diet and the development of precision nutrition models. Part II: Results. Advances in Nutrition. Nov 1;10(6):979-998. https://doi.org/10.1093/advances/nmz049
  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Dietary modulation of the gut microbiota to improve and sustain health: the gut microbiome. Nutrient delivery and impact on human health workshop sponsored by the International Center for Mechanical Sciences, Udine Italy
  • Type: Other Status: Published Year Published: 2019 Citation: Invited Speaker. Foods-Guts-Microbes. Pioneer High school Woodland, CA
  • Type: Journal Articles Status: Published Year Published: 2020 Citation: Solomon A. Mekonnen, Daniel Merenstein, Claire M. Fraser, and Maria L. Marco. 2020. Molecular mechanisms of probiotic prevention of antibiotic-associated diarrhea. Current Opinion in Biotechnology. 61:226-234


Progress 10/01/18 to 09/30/19

Outputs
Target Audience:Dietary bioactive chemicals are defined in this proposal as naturally occurring substances produced by plants or microbes that exert beneficial or undesirable effects when they are consumed or produced by human or microbial metabolism in the body. How these chemicals influence human health, disease development, and food safety is important to everyone. Understanding how to enhance the benefits or minimize the risks of specific dietary compounds is important for agricultural producers, food processors, healthcare professionals, and policy makers charged with determining optimal human nutrition requirements and maintaining the safety of the food supply. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?This project has provided training to visiting scholars, Postdoctoral Fellows, PhD students, technicians, and undergraduate student interns. The individuals on the project received training from Dr. Marco on probiotic bacteria, fermentable fibers, gut microbiology, and mechanisms of intestinal inflammation and diet-induced obesity. These individuals are responsible for conducting animal and bacteriology experiments well as analyzing results in cooperation with Dr. Marco. How have the results been disseminated to communities of interest?Dissemination events include conference presentations, published journal articles, and consultations with local and international food processors and members of the media. Dissemination of knowledge beyond a scientific audience has included on-site tours of the research laboratory and description of the research program to university students, international visitors, casual visitors to the university (members of the public) and stakeholders (representing industrial sectors related to food science, nutrition, and health). What do you plan to do during the next reporting period to accomplish the goals?Activities for the next reporting period encompass the further development of objective 1 to achieve the goals of the project. Specifically in Objective 1 we are examining the effects of phytochemicals and other dietary components on the gut microbiota and intestinal function. We will perform metagenome DNA sequencing to identify the functional genes present in human rodent intestinal contents. We will also perform gene knockout and overexpression studies to elucidate the specific mechanisms of beneficial bacteria function in the intestine.

Impacts
What was accomplished under these goals? Progress this year included experiments examining the impact of dietary fermentable fibers on the structure and function of the gut microbiome. We tested several forms of a dietary fiber known as a resistant starch to examine how the differences in fiber structure affect host cellular responses to diets high in animal protein and fats. The findings showed that not all forms of dietary fiber are equivalent in their capacity to modulate the gut microbiota, and correspondingly host responses. Our results show that dietary fiber containing multiple fiber types (e.g. in the form of whole grains) are most likely to benefit human health as indicated by they way they support gut microbiota diversity and intestinal cell responses via the production of SCFA and other metabolites. Also in our research, we continued to pursue the health-benefiting effects of probiotic bacteria. This work is aimed to mitigate the risks of Western diets high in fats and sugars and includes studies designed to uncover the mechanistic basis for probiotic conferred health benefits. Outputs on these studies included the completion of a PhD thesis on an antimicrobial made by certain probiotic Lactobacillus species and the development of a new direction investigating how the oxidation state of the intestine could alter probiotic and host cell responses. These findings show that specific bioactive compounds made by bacteria in fermented foods and the intestine are sufficient to improve gut barrier integrity and systemic metabolism.

Publications

  • Type: Conference Papers and Presentations Status: Published Year Published: 2018 Citation: Departmental seminar series invited speaker. Ecological and functional interactions of Lactobacillus plantarum in the digestive tract. Department of Food Science and Nutrition Colorado State University, Fort Collins, CO (2018 October 25)
  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Invited speaker. Improving health with microbes, Natural Products Expo, Anaheim, CA (2019 March 9)
  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Invited speaker. Use of Lactobacillus to off-set the effects of obesogenic diets, American Society for Microbiology Annual Conference, San Francisco, CA. (2019 June 22)
  • Type: Conference Papers and Presentations Status: Published Year Published: 2018 Citation: Zachary A. Bendiks, Justin Guice, Diana Carvajal-Aldez, Ryan Page, Anne M Raggio, Holiday A Durham, James Geaghan, David Welsh, Christopher Taylor, Meng Luo, Eugene Banks, Christine Pelkman, Claudia Husseneder, Roy Martin, Diana Coulon, Michael J Keenan, Maria L. Marco. Fermentable dietary fibers differentially alter the rat gut microbiome . FoodMicro 2018 (September 1-4, 2018).
  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Eric T. Stevens, Sara T. Sanz, Samuel H. Light, Caroline M. Ajo-Franklin, Maria L. Marco. Electro-fermentation potential of Lactobacillus plantarum. Molecular Foundry 2019 Annual User Meeting, Berkeley, CA (August 21-22, 2019).
  • Type: Theses/Dissertations Status: Published Year Published: 2019 Citation: Heeney, Dustin. Doctoral Dissertation. The bacterial protein targeted by the class IIb bacteriocin plantaricin EF and the potential of plantaricin EF to improve metabolic health (2019)
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Tina S. Nielsen, Zach Bendiks, Bo Thomsen, Matthew E. Wright, Peter K. Theil, Benjamin L. Scherer, and Maria L. Marco. 2019. High-amylose maize, potato and butyrylated starch modulate large intestinal fermentation, microbial composition and oncogenic miRNA expression in rats fed a high protein meat diet. International Journal of Molecular Sciences 20(9).


Progress 02/01/18 to 09/30/18

Outputs
Target Audience:Dietary bioactive chemicals are defined in this proposal as naturally occurring substances produced by plants or microbes that exert beneficial or undesirable effects when they are consumed or produced by human or microbial metabolism in the body. How these chemicals influence human health, disease development, and food safety is important to everyone. Understanding how to enhance the benefits or minimize the risks of specific dietary compounds is important for agricultural producers, food processors, healthcare professionals, and policy makers charged with determining optimal human nutrition requirements and maintaining the safety of the food supply. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?This project has provided training to visiting scholars, Postdoctoral Fellows, PhD students, technicians, and undergraduate student interns. The individuals on the project received training from Dr. Marco on probiotic bacteria, fermentable fibers, gut microbiology, and mechanisms of intestinal inflammation and diet-induced obesity. These individuals are responsible for conducting animal and bacteriology experiments well as analyzing results in cooperation with Dr. Marco. How have the results been disseminated to communities of interest?Dissemination events include conference presentations, published journal articles, and consultations with local and international food processors and members of the media. Dissemination of knowledge beyond a scientific audience has included on-site tours of the research laboratory and description of the research program to university students, international visitors, casual visitors to the university (members of the public) and stakeholders (representing industrial sectors related to food science, nutrition, and health). What do you plan to do during the next reporting period to accomplish the goals?Activities for the next reporting period encompass the further development of objective 1 to achieve the goals of the project. Specifically in Objective 1 we are examining the effects of phytochemicals and other dietary components on the gut microbiota and intestinal function. We will perform metagenome DNA sequencing to identify the functional genes present in human rodent intestinal contents. We will also perform gene knockout and overexpression studies to elucidate the specific mechanisms of beneficial bacteria function in the intestine.

Impacts
What was accomplished under these goals? Genomics methods were applied to determine how the gut microbiota respond to increased dietary fiber and to correlate those responses to reductions of obesity and type 2 diabetes risk in rodent models and humans. We tested the hypothesis that secreted peptides made by probiotic bacteria are effectors that modulate intestinal epithelial barrier function.

Publications

  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Dustin D. Heeney, Zhengyuan Zhai, Zach Bendiks, Javad Barouei, Alice Martinic, Carolyn Slupsky, and Maria L. Marco. 2018. Lactobacillus plantarum bacteriocin maintains epithelial barrier integrity to reduce diet-induced obesity. Gut Microbes https://doi.org/10.1080/19490976.2018.1534513
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Kara Marlatt, Ursula White, Robbie Beyl, Courtney Peterson, Corby Martin, Maria L. Marco, Michael Keenan, Roy Martin, Kayanush Aryana, and Eric Ravussin. 2017 Role of Resistant Starch on Diabetes Risk Factors in People with Prediabetes: Design, Conduct, and Baseline Results of the STARCH Trial. Journal of Contemporary Clinical Trials. 65:99-108. doi: 10.1016/j.cct.2017.12.005
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Courtney M. Peterson, Robbie A. Beyl, Kara L. Marlatt, Corby K. Martin, Kayanush J. Aryana, Maria L. Marco, Michael J. Keenan, and Eric Ravussin. Effect of 12 weeks of resistant starch supplementation on cardiometabolic risk factors in adults with prediabetes: a randomized controlled trial. American Journal of Clinical Nutrition 108(3) 492 -501. https://doi.org/10.1093/ajcn/nqy121
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Knud Erik Bach Knudsen, Helle N. Lærke, Mette Skou Hedemann, Tina Skau Nielsen, Anne Krog Ingerslev, Ditte Sivsø Gundelund, Peter K Theil, Stig Purup, Stine Hald, Anne Grete Schioldan, Maria L. Marco, Søren Gregersen, Kjeld Hermansen. Impact of diet-modulated butyrate production on intestinal barrier function and inflammation. Nutrients 10(10), 1499. https://doi.org/10.3390/nu10101499