Progress 10/01/19 to 09/30/20
Outputs
Target Audience:Research and information related to these projects was disseminated to a broad target audience of scientists, graduate students, and food scientists/food industry via webinar to the Society of Toxicology, a seminar for the Institute of Food Technologists, and as a seminar to faculty and graduate students at Washington State University. In addition, a more general audience was reached through interviews that Dr. Weir conducted for various health-related media outlets (ie. "Ask the Expert" column for The Caliper Currentnewsletter). Finally, aspects of the research conducted under this project have been the subject of multiple book chapters, peer-reviewed publications, and included in classroom curricula reaching an audience of mostly scientists and graduate/undergraduate students. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?This project has provided training opportunities for several graduate and undergraduate students to learn clinical skills such as phlebotomy, catheter placement, anthropometrics and vascular health assessment. Other students have had opportunities to become proficient in bioinformatics and integration of big datasets with experimental metadata. Finally, other students have had the opportunity to learn skills related to animal handling, vascular and metabolic assessment in animal models, and a variety of biochemical, immunologic, and molecular assays. How have the results been disseminated to communities of interest?Results of these studies have been disseminated through generation of the following types of media: peer-reviewed articles conference proceedings book chapters Seminars and talks given at Universities and Professional Societies Integration into course curricula Webinars Interviews for blogs and newsletters What do you plan to do during the next reporting period to accomplish the goals?Next reporting period we will be completing more collaborative studies that are designed to explore the role of various functional foods (blueberries, microgreens, and aronia berries) on vascular function and gut microbiota. We hope to translate what we have learned about the role of the microbiota in development of vascular impairments in animal models to human relevance with these studies. Specifically, we are planning to use fecal transplants from human clinical studies into germ free mice tomechanistically explore the role of blueberry consumption on vascular improvements. Similarly, the we are hoping to establish optimal doses and types of pulses for maximum metabolic benefits and translate these data from rodents to a human population. Finally, we are planning some basic microbiologic/cell biology studies exploring how cannabinoids interact reciprocally with human gut bacteria in anaerobic microcosms and establish how this influences functional outcomes on gut health.
Impacts
What was accomplished under these goals?
Under the objective 1: Examine the effects of phytochemicals and other dietary components on gut microbiota and intestinal function. Several human clinical trials have been completed that have focused on the interaction between dietary supplements and gut health. Specifically, we completed a 4-arm study that was analyzed as two separate trials examining the effects of a Phage-based "prebiotic" in combination with a Bifidobacterium probiotic, a Bifidobacterium probiotic alone, and a novel Bacillus subtilis probiotic on gut health, immune parameters, inflammation, and gut microbiota composition in comparison to a group consuming a placebo. We determined that: Bacillus subtilis DE111 improved lipid parameters, endothelial function, and modulated immune cell populations both in the basal state and in response to pro-inflammatory stimuli. A phage cocktail, PreforPro, when administered with a probiotic, extended benefits to gut health over consumption of the probiotic alone and favorably altered the gut microbiota toward a more anti-inflammatory state. Bifidobacterium lactis consumption improved several self-assessed parameters of intestinal health over placebo ingestion. In collaboration with Dr. Henry Thompson, we have established that dry bean and pulse consumption offsets the negative metabolic effects of a high fat diet in diet-induced obesity in rodent models and that these effects may be driven by alterations to the gut microbiota, in particular, increases in Akermansia muciniphila. This mucin-consuming species has been shown to improve metabolic parameters in clinical trials with obese humans as well. Finally, these studies have revealed that there are differences between types of legumes in terms of their impacts on the microbiota and metabolic health. Further research is being done to establish the mechanistic basis of these differences. Under Objective 2:Explore the interaction between dietary components and the host metabolome and epigenome. We completed two pilot clinical studies exploring the pharmacokinetics of different cannabidiol preparations and the individual factors (such as body composition) that may influence the absorption and clearance of these compounds in humans. Specifically, we found that water soluble preparations, when consumed as a beverage, had increased bioavailability over lipid soluble preparations, and that fat free mass was a significant predictorof time to peak concentration for the preparation that had the greatest Cmax.
Publications
- Type:
Journal Articles
Status:
Accepted
Year Published:
2020
Citation:
Johnson SA, Prenni J, Heuberger AL, Isweiri H, Chaparro J, Newman S, Uchanski M, Omerigic H, Michell K, Bunning M, Foster MT, Thompson HJ, Weir TL. Comprehensive Evaluation of Metabolites and Minerals in Six Microgreen Species and the Influence of Maturity. Current Development in Nutrition (in press)
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2020
Citation:
Weir TL, McGinley JN, Neil ES, Thompson HJ (2020) Effect of pulse consumption on obesity and the metagenome, Proceedings of the 1st International Conference on Nutrients- Nutrition and Microbiota Effects on Chronic Disease. doi:10.3390/IECN2020-07009
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Soderborg TK, Carpenter C, Janssen RC, Weir TL, Young BE, Krebs NF, Hernandez TL, Barbour LA, Frank DN, Kroehl M, Friedman JE. (2020) Gestational diabetes is uniquely associated with altered early seeding of the infant gut microbiota. Front Endocrinol doi:10.3389/fendo.2020.603021
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Grubb DS, Wrigley SD, Freedman KE, Wei Y, Vazquez AR, Trotter RE, Wallace TC, Johnson SA and Weir TL (2020) PHAGE-2 Study: Supplemental Bacteriophages Extend Bifidobacterium animalis subsp. lactis BL04 Benefits on Gut Health and Microbiota. Nutrients 12, 2474; doi:10.3390/nu12082474
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Weir TL, Trikha SRJ, Thompson HJ (2020) Diet and Risk of Cancer Reduction: The Role of Diet-Microbiota Interactions and Microbial Metabolites. Seminars in Cancer Biology DOI: 10.1016/ j.semcancer.2020.06.007
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Trotter RE, Vazquez AR, Grubb D, Freedman KE, Wei Y, Jones S, Gentile CL, Melby CL, Johnson SA, Weir TL (2020) Examining the Impact of Probiotic Supplement Intake on Endothelial Function and Lipid Metabolism in Healthy Adults. Beneficial Microbes 11 (7): 621-630.
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Lee DM, Ecton K, Trikha SR, Wrigley SD, Thomas K, Battson M, Wei Y, Johnson SA, Weir TL, and Gentile CL. (2020) Microbial Metabolite Indole-3-Propionic Acid Supplementation Does Not Protect Mice from the Cardiometabolic Consequences of a Western Diet. Am J Physiol-Gastro Liver Physiol doi.org/10.1152/ajpgi.00375.2019
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Hobbs JM, Vazquez AR, Remijan ND, Trotter RE, McMillan TV, Freedman K, Wei Y, Arnold OR, Wolfe LM, Johnson SA, and Weir TL (2020) Evaluation of Pharmacokinetics and Acute Anti-Inflammatory Potential of Two Oral Cannabidiol (CBD) Preparations. Phytotherapy Research
DOI:10.1002/ptr.6651
- Type:
Journal Articles
Status:
Accepted
Year Published:
2020
Citation:
9. Michell KA*, Isweiri H, Newman SE, Bunning M, Bellows LM, Dinges ME*, Grabos LE*, Rao S, Foster MT, Heuberger AL, Prenni JE, Thompson HJ, Uchanski ME, Weir TL, Johnson SA (2020) Microgreens for the Masses: Exploring Consumer Acceptance and Sensory Perceptions of an Emerging Functional Food Crop. Journal of Food Science
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
McGinley JN, Fitzgerald VK, Neil ES, Omerigic HM, Heuberger AL, Weir TL, McGee R, Vandermark G, Thompson HJ. (2020) Pulse Crop Effects on the Gut Microbial Populations, Intestinal Function, and Adiposity in a Mouse Model of Dietary Induced Obesity. Nutrients 12:593; doi: 10.3390/nu12030593
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2020
Citation:
Thompson HJ, McGinley JN, Neil ES, Weir TL. (2020) Effect of common bean consumption on the gut associated microbiome in an in vivo screening model for breast cancer. Proceedings of the 1st International Conference on Nutrients- Nutrition and Microbiota Effects on Chronic Disease. doi: 10.3390/IECN2020-07008.
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Progress 10/01/18 to 09/30/19
Outputs
Target Audience:We reached an audience of scientists through participation in departmental seminars at the University of Colorado-Anschutz campus and the University of Nebraska. In addition, Dr. Weir presented this research to lay audiences through two public podcasts (BIOHM and PATH). Finally, several students and collaborators presented posters at national conferences, including the American Society of Nutrition meeting. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Several graduate students have been trained in conducting studies in both human and animal models, sequence data analysis and metabolomics. In addition, one undergraduate conducted his capstone project and was awarded an undergraduate fellowship from ASM, which will allow him to present his research at a national conference and attend a leadership workshop. How have the results been disseminated to communities of interest?Results have been disseminated through PI, collaborators, and students presenting seminars, giving webinars and podcasts, and through poster presentations at local and national meetings. In addition, the PI and collaborators have incorporated research findings into class materials for graduates and undergraduates. What do you plan to do during the next reporting period to accomplish the goals?Objective 1. We are completing two studies assessing probiotic efficacy in reducing gut symptoms and inflammation as well as whether they enhance immune modulation (to be assessed by flow cytometry and in LPS stimulated PBMCs) and cardiovascular functioning. Objective 2. We are establishing a cell co-culture model with Caco-2 cells acting as an intestinal barrier and HUVECs serving as vascular endothelial cells. In this system, we can look at how various elicitors affect intestinal barrier function and identify molecules that pass the epithelial barrier to interact with endothelial cells in a manner that would alter vascular function (i.e. NO signaling, ROS generation, ER stress inducers). In addition, we will further explore the role of LPS and TLR signaling in gut-epithelial cell crosstalk in pre-clinical animal knockout models.
Impacts
What was accomplished under these goals?
OBJECTIVE 1. Examine the effects of phytochemicals and other dietary components on gut microbiota and intestinal function. Our laboratory has continued to conduct human clinical trials with functional foods and dietary supplements. This year we have completed a small pilot study looking at the pharmacokinetics of oral cannabidiol preparations and assessing their anti-inflammatory potential. We are also analyzing data from two nearly completed clinical studies of probiotics on gut function and cardiovascular and immune parameters. Finally, we have been collaborating with Dr. Sarah Johnson to assess how dietary interventions with functional foods like blueberries, aronia berries, red beetroot juice, and microgreens alter oral and gut microbiota and how the bioavailability of the bioactive compounds in these foods is influenced by gut and oral microbial communities. In our human clinical studies, we have established differences in oral bioavailability of two commercial cannabinoid (CBD) preparations and established that CBD reduces inflammatory markers in LPS-stimulated PBMCs isolated from humans 90 minutes after a single oral dose. Further we have identified sex-based differences in the oral microbiota and are examining whether these differences influence chronic response of oral nitrate-reducing bacteria to chronic beetroot juice consumption. As these are both popular dietary supplements, these data are important to inform consumers regarding the bioavailability and bioactivity of these supplements. OBJECTIVE 2. Identify cellular mechanisms and host molecular targets of beneficial or adverse dietary components that influence human health. Cardiovascular disease is leading cause of death in the US among both men and women and vascular dysfunction, measured as arterial stiffness and endothelial dysfunction, are good predictors of future cardiovascular events. We have evidence suggesting that the microbiota is a key regulator driving vascular dysfunction. Most recently, we have begun to translate pre-clinical models to human health relevance by utilizing human/mouse crossover models and collecting baseline data on human microbiota and vascular dysfunction. We have observed that microbiota from humans with dysfunctional or normal vascular function can recapitulate these phenotypes when colonized in germ free mice. We have also identified some microbial signatures of human vascular function and are beginning to explore potential mechanistic links based on microbial metabolites such as secondary bile acid, nitrate reduction, and SCFA production effects in a dual cell culture (intestinal epithelial cells and vascular endothelial cells) system. Our work in establishing the microbiota as a causal factor in vascular dysfunction, an early marker of human cardiovascular disease, will help identify new modalities for preventing or reversing vascular impairments to reduce the overall risk of later CVD development.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Hamm AK and Weir TL (2019) Spent hops as a source of novel prenylflavonoids for human health. Acta Horticulturae 1236: 75-84.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
4. Brunt VE, Gioscia-Ryan RA, Richey JJ, Zigler MC, Cuevas LM, Gonzalez A, Vazquez-Baeza Y, Battson ML, Smithson AT, Gilley AD, Ackermann G, Neilson AP, Weir TL, Davy KP, Knight RL, Seals DR. (2019) Gut dysbiosis induces arterial dysfunction and oxidative stress with aging in mice. J Physiol https://doi.org/10.1113/JP277336.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
3. Febvre HP, Rao S, Gindin M, Goodwin NM, Vivanco JS, Manter DK, Wallace TC, Weir TL. (2019) PHAGE: Effects of bacteriophage consumption on gut microbiota, inflammation, and lipid metabolism. Nutrients 11 (3): 666. https://doi.org/10.3390/nu11030666.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
3. Neil ES, McGinley JN, Fitzgerald VK, Lauck CA, Tabke JA, Streeter-McDonald MR, Broeckling CD, Weir TL, Foster MT, Thompson HJ. Common bean (Phaseolus vulgaris L.) consumption reduces fat accumulation in a polygenic mouse model of obesity. Nutrients doi: 10.3390/nu11112780
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Progress 12/12/17 to 09/30/18
Outputs
Target Audience:This multistate project has broadly defined objectives related to food and food compounds on various aspects of health. Thus, the target audience includes anyone interested in how food, the compounds in food, and processing of food affect human health could be considered part of the target audience. Specifically, the contributions of my group include examining how supplements and dietary components influence the gut microbiota and how, in turn, the gut microbiot6a impacts chronic disease development. The specific audience for this work ithis reporting period has included, food technologits that are interested in development of novel gut-targeted therapeutics, alternative medicine practioners, dieticians, lactation consultants, and other medical professionals. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?This project has provided several students from undergraduate through graduate level an opportunity to train in aspects of human clinical research (ethics, blood collection, anthropometrics, clinical data collection, etc) as well as preclinical animal studies and basic DNA and culture based microbiology techniques. How have the results been disseminated to communities of interest?Results have been disseminated through various venues. Dr. Weir includes outcomes of her research in several of her classes, including Probiotics and Phytochemicals for Health and Fermentation Microbiology. In addition, she serves as an advisory board member of the Rocky Mountain Children's Health Foundation - Mother's Milk Bank and has spoken at several events that they have sponsored, including the Lactation Journal Club, the Northern Colorado Breastfeeding Coalition, and the Human Milk Banking Association of North America. She has lectured at the Osher Lifelong Learning Institute as well as at Nutrition, Food Science, and Sports Medicine conferences both nationally and internationally. Finally, results have been dissemiinated through a CSU extension publication and several peer-reviewed scientific publuications. What do you plan to do during the next reporting period to accomplish the goals?We plan to explore the role of cricket chitin in modulating the gut microbiota and begin to examine mechanistically how cricket consumption might reduce inflammation a nd modulate the immune system. We have submitted a proposal to the Global Grants for Gut Health challenge proposing to use a series of in vitro microbiological and cell culture assays as well as follow-up human feeding studies to examine these parameters. We are also continuing to explore the link between vascular function and gut microbiota by examining correlations between vascular function parameters and specific bacterial population sin humans. We are also using germ-free mice populated with human microbes to further examine the cause and effect relationship of this system.
Impacts
What was accomplished under these goals?
OBJECTIVE 1. Examine the effects of phytochemicals and other dietary components on gut microbiota and intestinal function. As the global population continues to grow, there is an urgent need to identify ways to provide a safe and secure foods supply that minimizes impacts on the environment. Edible insects are being explored as a potential low input food source to address this growing worldwide issue. Many edible insects provide more nutrients, including protein, on a dry weight basis than traditional livestock. We were interested in exploring the safety and tolerability of insect consumption in a western population and determine whether insects offer health benefits beyond nutrition. We determined in a pilot cohort of healthy adults that consumption of 25g/day of cricket powder was safe and tolerable. In addition, there was an increase in beneficial Bifidobacterium measured in stool samples and reductions in the circulating inflammatory marker TNF-a. Future studies will be aimed at determining whether cricket chitin is a prebiotic fiber source and examining whether cricket consumption protects against environmental enteropathy in vulnerable populations. OBJECTIVE 2. Identify cellular mechanisms and host molecular targets of beneficial or adverse dietary components that influence human health. Cardiovascular disease is leading cause of death in the US among both men and women and vascular dysfunction, measured as arterial stiffness and endothelial dysfunction, are good predictors of future cardiovascular events. Through collaborative studies utilizing antibiotics and microbiota transplantations, we have determined that gut microbiota play a role in development of vascular dysfunction. We are currently exploring mechanisms, such as microbiota-driven modulation of gut barrier function and microbiota-derived metabolites on host inflammatory and immune status as potential mechanisms driving this relationship.
Publications
- Type:
Book Chapters
Status:
Awaiting Publication
Year Published:
2018
Citation:
Cox-York KC, Stoecker E, Hamm AK, Weir TL (2018) Microbial Metabolites in Cancer Promotion or Prevention. In: Microbiome and Cancer (ed. Robertson ES). Springer International Publishing, Cham, Switzerland.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Gentile CL and Weir TL (2018) The gut microbiota at the intersection of diet and health. Science 362 (6416): 776-780.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Soderborg TK, Mulligan CE, Clark SE. Babcock L, Janssen RC, Lemas DL, Johnson LK, Frank DN, Weir TL, Barbour LA, Hernandez TL, Kuhn KA, DAlessandro A, El Kasim KC, Friedman JE (2018) The Gut Microbiota in Infants of Obese Mothers Increases Hepatic Inflammation and Susceptibility to Obesity and NAFLD in Germ-free Mice. Nature Communications 9(1):4462.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Stull VJ, Finer E, Bergmans RS, Febvre HP, Longhurst C, Manter DK, Patz J, Weir TL. (2018) Impact of Edible Cricket Consumption and Gut Microbiota in Healthy Adults, a Double-blind Crossover Trial. Scientific Reports. 8, 10762
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Lee DM, Battson ML, Jarrell DK, Hou S, Ecton KE, Weir TL, Gentile CG. (2018) SGLT2 inhibition via dapagliflozin improves generalized vascular dysfunction and alters the intestinal microbiota in type II diabetic mice. Cardiovascular Diabetology, 17:62.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Gindin M, Febvre HP, Rao S, Wallace TC, Weir TL. (2018) Bacteriophage for Gastrointestinal Health (PHAGE) Study: Evaluating the Safety and Tolerability of Supplemental Bacteriophage Consumption. Journal of the American College of Nutrition. Doi: 10.1080/07315724.2018.1483783.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Battson ML, Lee DM, Weir TL, Gentile CG (2018) The gut microbiota as a novel regulator of cardiovascular function and disease. Journal of Nutritional Biochemistry 56: 1-15.
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Battson ML, Lee DM, Jarrell D, Hou S, Ecton K, Weir TL, Gentile CG (2017) Suppression of Gut Dysbiosis Reverses Western Diet-Induced Vascular Dysfunction. Am J Physiol- Endocrinol & Metabol doi: 10.1152/ajpendo.00187.2017
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