Progress 10/01/19 to 09/30/20
Outputs
Target Audience:Peer-reviewed publications from this project have targeted audiences from the biomedical sciences disciplines, including faculty and scientists. Whereas non-scientist audiences were reached through public presentations, local research symposiums, and engagement with the lay media. Changes/Problems:No changes to project objectives have occurred. However, our team was adversely impacted by the global pandemic of COVID-19. The pandemic forced a "pause"of all in-person research activities from approximately March 2020 through August 2020. From August 2020 through present, institutional guidelines limited the density of research personnal on campus. These restrictions have caused delays in research participant recruitment, hindered in-person activities that were critical for growing deuterium-labeled spinach and conducting experiments, and prevented genomic sequencing of gut microbiota due to the closure of campus core laboratories. During the closure period, research personnel focused primarily on data analysis and authoring manuscripts. Restoration of research activities is expected at least in part during the next reporting period. What opportunities for training and professional development has the project provided?Throughout the course of these projects, training opportunities were provided to undergraduate students, graduate students, and post-doctoral scholars. Persons involved in clinical research projects gained experience in regulatory documenation, phlebotomy, biospecimen collection and processing, and advanced mass spectrometry. Persons involved in rodent studies gained experience in animal husbandry, diet formulation, surgical techniques, and biomolecular techniques including HPLC, protein and gene expression tools, and spectrophotometry. How have the results been disseminated to communities of interest?Dissemination has occurred primarily through the publication of research findings in peer-reviewed scientific journals. Dr. Bruno as well as research personnel associated with the project have also provided lay presentations, engaged with the media, and communicated research findings at national/international scientific conferences. What do you plan to do during the next reporting period to accomplish the goals?A primary focus will be to complete metagenomic studies to characterize the influence of the gut microbiome on green tea catechin bioavailability in healthy persons and persons with obesity. We are also actively completing randomized controlled trials focusing on the gut-level benefits of green tea polyphenols to alleviate gut permeability and metabolic endotoxemia in persons with metabolic syndrome. Separate clinical studies are also examining dairy milk phospholipids to alleviate gut-level inflammatory responses that provoke metabolic endotoxemia. We are also establishing new in-house technology to growdeuterium-labeled spinach for clinical trials examining egg phospholipids to potentiate the bioavailability of spinach-derived deuterium-labeled vitamin E and vitamin K.
Impacts
What was accomplished under these goals?
Under Aim 1, our team completed a pharmacokinetic study in persons with obesity compared with healthy adults to examine the bioavailability and metabolism of green tea catechins. In the fasted state, participants ingested a gelatin confection containing green tea polyphenols prior to blood and urine collection at timed intervals for 24-hours; a fecal sample was also collected prior to study initiation. The bioavailability of plasma catechins was lower among persons with obesity and occurred independent of any differences in their urinary elimination. Pharmacokinetic profiles suggest that catechins were absorbed to a lesser extent, but this was not accompanied by the greater generation of microbial-derived catechin metabolites (i.e. valerolactones). Analysis of gut microbial community structure and function as well as advanced mathematical modeling are underway to inform precision nutrition applications and dietary recommendations. Under Aim 2,a study in rodents was conducted to examine the structure/function hepatoprotective benefits of epigallocatechin gallate (EGCG) and (+)-catechin relative to green tea extract (GTE). Mice were fed a low-fat (LF) diet, or a high-fat (HF) diet devoid of or containing 2% GTE, 0.3% EGCG, or 0.3% (+)-catechin.GTE prevented HF-induced obesity to a greater extent than EGCG and CAT, whereas GTE andEGCG more favorably attenuated insulin resistance. GTE, EGCG and CAT similarly attenuated serum alanine aminotransferase and serum endotoxin, but only GTEand EGCG fully alleviated HF-induced NASH. However, hepatic TLR4/NFκB inflammatory responses that were otherwise increased in HF mice were similarlyattenuated by GTE, EGCG and CAT. Each treatment also similarly prevented the HF-induced loss in expression of intestinal TJPs and hypoxia inducible factor-1α and the otherwise increased levels of ileal and colonic TNFα mRNA and fecal calprotectin protein concentrations. Gut microbial diversity that was otherwise lowered in HF mice was maintained by GTE and CAT only. Further, microbial metabolic functions were more similar between GTE and CAT. Collectively, GTE catechins similarly protect against endotoxin-TLR4-NFκB inflammation in NASH, but EGCG and CAT exert differential prebiotic and antimicrobial activitiessuggesting that catechin-mediated shifts in microbiota composition are not entirely responsible for their benefits along the gut-liver axis.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
P Dey, JB Kim, C Chitchumroonchokchai, J Li, GY Sasaki, BD Olmstead, KL Stock, JM Thomas-Ahner, SK Clinton, RS Bruno. (2019). Green tea extract inhibits early oncogenic responses in mice with nonalcoholic steatohepatitis. Food Funct, 10, 6351-6361.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
GY Sasaki, J Li, MJ Cichon, KM Riedl, RE Kopec, RS Bruno. (2019). Green tea extract treatment in obese mice with nonalcoholic steatohepatitis restores the hepatic metabolome in association with limiting endotoxemia-TLR4-NFkB-mediated inflammation. Mol Nutr Food Res, 63(24):e1900811. doi: 10.1002/mnfr.201900811.
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
BK Alba, AE Stanhewicz, P Dey, RS Bruno, WL Kenney, LM Alexander. (2020). Controlled feeding of an 8-day high dairy cheese diet prevents sodium-induced endothelial dysfunction in the cutaneous microcirculation through reductions in superoxide. J Nutr, 150(1):55-63; doi: 10.1093/jn/nxz205.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
KM Hirahatake, RS Bruno, BW Bolling, C Blesso, LM Alexander, SH Adams. (2019). Dairy foods and dairy fats: new perspectives on pathways implicated in cardiometabolic health. Adv Nutr, 11(2):266-279. doi: 10.1093/advances/nmz105.
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
KM Ranard, MJ Kuchan, RS Bruno, JM Juraska, JW Erdman. (2020). Synthetic a-tocopherol, compared with natural a-tocopherol, downregulates myelin genes in cerebella of adolescent Ttpa-null mice. J Nutr, 150(5):1031-1040. doi: 10.1093/jn/nxz330.
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
JK Hodges, J Zhu, Z Yu, Y Vodovotz, G Brock, GY Sasaki, P Dey, RS Bruno. (2020) Intestinal-level anti-inflammatory bioactivities of catechin-rich green tea: Rationale, design, and methods of a double-blind, randomized, placebo-controlled crossover trial in metabolic syndrome and healthy adults. Contemp Clin Trials Commun. 17:100495. doi: 10.1016/j.conctc.2019.100495
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
MM Kemski, CA Rappleye, K Dabrowski, RS Bruno, M Wick. (2020). Transcriptomic response to soybean meal-based diets as the first formulated feed in juvenile yellow perch (Perca flavescens). Sci Rep, 10(1):3998. doi: 10.1038/s41598-020-59691-z.
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
MJ Kuchan, KM Ranard, P Dey, S Jeon, GY Sasaki, KJ Schimpf, RS Bruno, M Neuringer, JW Erdman Jr. (2020). Infant rhesus macaque brain a-tocopherol stereoisomer profile is differentially impacted by source of a-tocopherol in infant formula. J Nutr, doi: 10.1093/jn/nxaa174.
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
P Dey, BD Olmstead, GY Sasaki, Y Vodovotz, Z Yu, RS Bruno (2020). Epigallocatechin gallate but not catechin prevents nonalcoholic steatohepatitis in mice similar to green tea extract while differentially affecting the gut microbiota. J Nutr Biochem, doi: 10.1016/j.jnutbio.2020.108455.
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
WR Quarles, A Pokala, E Shaw, J Ortega, L Hillman, R Jimenez-Flores, RS Bruno. (2020). Alleviation of metabolic endotoxemia by milk fat globule membrane: Rationale, design, and methods of a double-blind, randomized controlled, crossover dietary intervention trial in adults with metabolic syndrome. Curr Dev Nutr, 4(9):nzaa130. doi: 10.1093/cdn/nzaa130.
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
JK Hodges, GY Sasaki, RS Bruno. (2020). Anti-inflammatory activities of green tea catechins along the gut-liver axis in nonalcoholic fatty liver disease: lessons learned from preclinical and human studies. J Nutr Biochem, 2020;85:108478. doi: 10.1016/j.jnutbio.2020.108478.
- Type:
Book Chapters
Status:
Published
Year Published:
2019
Citation:
P Dey, GY Sasaki, RS Bruno. (2019). Green Tea: Composition, Metabolism, Bioavailability and Role in Preventing Chronic Diseases. In: Handbook of Nutraceuticals and Functional Foods, 3rd Edition (REC Wildman and RS Bruno, ed). In Press
- Type:
Book Chapters
Status:
Published
Year Published:
2019
Citation:
RS Bruno. (2019). The role of a- and g-tocopherols in health. In: Handbook of Nutraceuticals and Functional Foods, 3rd Edition (REC Wildman and RS Bruno, ed). In Press.
- Type:
Book Chapters
Status:
Published
Year Published:
2019
Citation:
RS Bruno. (2019). Vitamin E and Metabolic Syndrome. In: Vitamin E in Human Health (Weber, Blumberg, Frank, eds). Springer Nature Switzerland. doi: 10.1007/978-3-030-05315-4_22.
- Type:
Book Chapters
Status:
Published
Year Published:
2020
Citation:
MG Traber and RS Bruno. (20202). Vitamin E. In: Present Knowledge and Nutrition, 11th edition.
- Type:
Books
Status:
Accepted
Year Published:
2019
Citation:
REC Wildman and RS Bruno. (2019). Handbook of Nutraceuticals and Functional Foods, 3rd Edition, Taylor and Francis (New York).
- Type:
Conference Papers and Presentations
Status:
Other
Year Published:
2019
Citation:
RS Bruno. (2019). Dietary Management of NASH with Green Tea: Lessons Learned From Preclinical Models. 5th Annual Guangzhou Nutrition Symposium; Guangzhou, China.
- Type:
Conference Papers and Presentations
Status:
Other
Year Published:
2019
Citation:
RS Bruno. (2019). Dysregulated Bioavailability of Vitamin E Along The Gut-Liver Axis In Adults With Metabolic Syndrome. Chinese Academy of Science; Shanghai, China.
- Type:
Other
Status:
Other
Year Published:
2020
Citation:
RS Bruno. (2020). Bioactive Food Components & Cardiometabolic Health: A Focus On The Gut-Liver Axis. Department of Nutritional Sciences, University of North Carolina-Greensboro; Greensboro, NC.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2020
Citation:
X Sun, P Dey, RS Bruno, J Zhu. 2019. Investigating the metabolic impact of green tea extract and its major constitutes on gut microbial metabolism in obese mice model. Joint Meeting of the Inaugural Conference on Personalized Food and Nutritional Metabolomics for Health and 14th Annual Mass Spectrometry Symposium (Columbus, OH). Abstract/Poster.
- Type:
Theses/Dissertations
Status:
Published
Year Published:
2020
Citation:
Geoff Sasaki. (2020). Dietary green tea to attenuate metabolic endotoxemia-associated inflammation along the gut-liver axis. Doctoral Dissertation, The Ohio State University.
- Type:
Theses/Dissertations
Status:
Published
Year Published:
2019
Citation:
Bryan Olmstead. (2019). Independent Bioactivities of Green Tea Catechins On Gut Health During NASH. Master of Science Thesis, The Ohio State University.
- Type:
Theses/Dissertations
Status:
Published
Year Published:
2020
Citation:
Emily Shaw. (2020). Dietary incorporation of potato-resistant starch as part of a Dietary Guidelines for Americans diet on cardiometabolic responses along the gut-liver axis in metabolic syndrome. Master of Science Thesis, The Ohio State University.
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Progress 10/05/18 to 09/30/19
Outputs
Target Audience:Target audiences were primarily biomedical scientists who were reached by disseminating peer-reviewed publications of scientific findings associated with this project. In addition, non-scientist lay audiences were reached by public presentation outreach efforts. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?These projects have provided training opportunities for undergraduate and graduate students as well as a post-doctoral scholar. Individuals involved in human studies have become trained in procedures to perform controlled human studies with scientific rigor, how to manage regulatory documents, perform HPLC analyses, and metagenomic sequencing. Individuals engaged in preclinical studies in mice have become proficient in performing biomolceular techniques including Western blotting to quantify protein expression, quantitiative RT-PCR to quantify gene expression, and spectrophotometric techniques that quantify biomarkers of metabolic derrangements. How have the results been disseminated to communities of interest?Outreach activites have included providing invited lay and scientific presentations to educate audiences. Dr. Bruno has also been interviewed by the lay media and summaries of published reports have appeared in the lay press. What do you plan to do during the next reporting period to accomplish the goals?Our team remains active in completing our human studies examining green tea bioavailability. We also plan to complete recruitment for a randomized controlled trial examining green tea catechins to alleviate metabolic endotoxemia in obese adults. The collection of these studies are expected to provide immediate research translation to support evidence-based dietary recommendations to alleviate endotoxemia-associated inflammatory responses that are highly implicated in cardiometabolic disorders (e.g. diabetes, fatty liver, cardiovascular disease, metabolic syndrome).
Impacts
What was accomplished under these goals?
Under Aim 1, our team is actively conducting pharmacokinetic studies in obese and lean humans to examine the extent to which the bioavailability of green tea catechins is affected by health status. Age- and gender-matched obese and lean adults (18-60 y) were recruited from the Columbus, Ohio area. On a single occassion, they ingested green tea catechins (provided as part of a gelatin-based confection) and blood samples were collected for timed intervals for 12 hours and urine was collected for 24 h. In addition, fecal samples were collected for the 48 hours preceding the pharmacokinetics trial to perform 16S metagenomic sequencing of gut microbiota. Biospecimen analysis is underway, and preliminary data indicate that catechin bioavailability is poorer among obese adults based on their lower Cmax and area under the catechin concentration curve responses.In addition, obese adults had increased absorption of gut-derived microbial metabolites (e.g. valerolactones) of green tea catechins. Completion of this study during the next reporting period is expected to fully define catechin pharmacokinetic responses (e.g. rates of absorption and elimination; half-lives) in relation to markers of gut barrier integrity and microbiota composition. Under Aim 2, studies in mice were conducted to examine the extent to which green tea extract (GTE) protects against the absorption of gut-derived endotoxins that are known to mediate obesity risk by inducing Toll-like receptor-4/nuclear factor kappaB (TLR4/NFκB) inflammation. Mice were fed a low-fat or high-fat (HF) diet containing 0% or 2% GTE for 8 weeks. At Week 7, fluorescein isothiocyanate (FITC)-dextran was administered by oral gavage before assessing its serum concentrations as a gut permeability marker. Our published findings demonstrated that HF-feeding increased adipose mass and adipose expression of genes involved in TLR4/NFκB-dependent inflammation and macrophage activation. GTE attenuated HF-induced obesity and pro-inflammatory gene expression. GTE in HF mice decreased the absorption of FITC-dextran and attenuated portal vein and circulating endotoxin concentrations. GTE in HF mice also prevented HF-induced decreases in intestinal tight junction proteins and hypoxia inducible factor-1α while preventing increases in TLR4/NFκB-dependent inflammatory genes. Gut microbiota analysis indicated that GTE improved gut microbial diversity, decreased gut dysbiosis, and increasedspecific populations of commensal bacteria. These findings support that GTE protects against obesity consistent with a mechanism involving the gut-adipose axis that limits endotoxin translocation and consequent adipose TLR4/NFκB inflammation by improving gut barrier function.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
M Goodus, A Sauerbeck, PG Popovich, RS Bruno, DM McTigue. (2018). Dietary green tea extract prior to spinal cord injury prevents hepatic iron overload but does not improve chronic hepatic and spinal cord pathology in rats. J Neurotrauma, 35(24):2872-2882.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
JD McDonald, E Mah, C Chitchumroonchokchai, EJ Reverri, J Li, JS Volek, FA Villamena, RS Bruno. (2018). Co-ingestion of whole eggs or egg whites with glucose protects against postprandial hyperglycemia-induced oxidative stress and dysregulated arginine metabolism in association with improved vascular endothelial function in prediabetic men. Br J Nutr, 120(8):901-913.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
JD McDonald, E Mah, C Chitchumroonchokchai, P Dey, AN Labyk, FA Villamena, JS Volek, RS Bruno (2018). Dairy milk proteins attenuate hyperglycemia-induced impairments in vascular endothelial function in adults with prediabetes by limiting increases in glycemia and oxidative stress that reduce nitric oxide bioavailability. J Nutr Biochem, 63:165-176.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
R Pei, DM DiMarco, KK Putt, DA Martin, C Chitchumroonchokchai, RS Bruno, BW Bolling (2018). Pre-meal low-fat yogurt consumption reduces postprandial inflammation and markers of endotoxin exposure in healthy premenopausal women in a randomized controlled trial. J Nutr, 148:1-7.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
M Xu, F Zhong, RS Bruno, KD Ballard, J Zhang, J Zhu. (2018). Comparative metabolomics elucidates postprandial metabolic modifications in plasma of obese individuals with metabolic syndrome. J Proteome Res, 17(8):2850-2860.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
JD McDonald, E Mah, P Dey, BD Olmstead, GY Sasaki, FA Villamena, RS Bruno. (2018). Dairy milk, regardless of fat content, protects against postprandial hyperglycemia-mediated impairments in vascular endothelial function in adults with prediabetes by limiting oxidative stress responses that reduce nitric oxide bioavailability. J Nutr Biochem, 63:129-139.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
MG Traber, GR Buettner, RS Bruno. (2019). The relationship between vitamin C status, the gut-liver axis, and metabolic syndrome. Redox Biology, 21:101091. doi: 10.1016/j.redox.2018.101091
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
I Hatsu, C Gunther, E Hade, S Vandergriff, N Slesnick, R Williams, R Bruno, J Kennel. (2019). Unaccompanied homeless youth have extremely poor diet quality and nutritional status. Int J Adol Youth, 24:3, 319-332. doi: 10.1080/02673843.2018.1538885
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
P Dey, GY Sasaki, P Wei, L Wang, J Li, C Chitchumroonchokchai, J Zhu, D McTigue, Z Yu, RS Bruno. (2019). Green tea extract prevents obesity in male mice by alleviating gut dysbiosis in association with improved intestinal barrier function that limits endotoxin translocation and adipose inflammation. J Nutr Biochem, 67:78-89.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
LE Griffin, DW Fausnacht, JL Tuzo, AK Addington, KC Racine, H Zhang, MD Hughes, KM England, RS Bruno, SF OKeefe, AP Neilson, AC Stewart. (2019). Flavanol supplementation protects against obesity-associated increases in systemic IL-6 levels without inhibiting body mass gain in mice fed a high-fat diet. Nutr Res, 66:32-47.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
R Williams, A Rose, RS Bruno, A Hanks, J Kennel, J McDonald, C Gunther. (2019). Examination of the relationship of diet quality with cardiometabolic risk factors in apparently healthy college students. J Am Coll Health, 8:148. doi: 10.4103/jehp.jehp_12_19.
- Type:
Theses/Dissertations
Status:
Published
Year Published:
2019
Citation:
Neuroprotection by gamma-Tocopherol in Lean and Obese Murine Models of Ischemic Stroke
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