Source: WASHINGTON STATE UNIVERSITY 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
HATCH
Reporting Frequency
Annual
Accession No.
0232953
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
W-3122
Project Start Date
Feb 1, 2013
Project End Date
Sep 30, 2017
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
WASHINGTON STATE UNIVERSITY
240 FRENCH ADMINISTRATION BLDG
PULLMAN,WA 99164-0001
Performing Department
School of Food Science
Non Technical Summary
Grape seed and skin contains high amounts of polyphenolic compounds that are known for their anti-oxidative and anti-inflammatory effects, and grape seed extract (GSE) has been developed into a dietary supplement. However, the molecular mechanisms associated with the beneficial effects of GSE have not been well defined. Considering that polyphenolic compounds have antimicrobial and possibly prebiotic functions, their consumption are expected to modulate gut microbial composition. Gut microbiota is increasingly recognized as an important player in gut epithelial integrity and impaired intestinal epithelial barrier function is involved in the pathogenesis of inflammatory bowel disease, food allergies, type 1 diabetes and other autoimmune diseases. On the other hand, absorbed polyphenolic compounds are also expected to exert a number of beneficial systemic effects, including prevention of cancer, cardiovascular disease, obesity and diabetes. Our objectives are to elucidate the mechanisms responsible for the beneficial effects of polyphenolic compounds on intestinal barrier function, inflammation and overall health, which will not only be applicable to polyphenolic compounds in grape but other fruits as well.
Animal Health Component
80%
Research Effort Categories
Basic
20%
Applied
80%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
7021139104050%
7023840104050%
Knowledge Area
702 - Requirements and Function of Nutrients and Other Food Components;

Subject Of Investigation
3840 - Laboratory animals; 1139 - Grapes, general/other;

Field Of Science
1040 - Molecular biology;
Goals / Objectives
Determine the mechanisms by which dietary bioactive compounds protect against human diseases. Discover and characterize novel bioactive dietary compounds that have beneficial or adverse effects on human health.
Project Methods
Washington State University groups will study the biological effects of grape seed extract (GSE) and other dietary bioactive components/extracts on gut microbial composition, intestinal epithelial barrier function and overall health and further explore associated signaling and underlying mechanisms using in vivo mice model and in vitro cell culture. By employing wild type and transgenic mice, we will examine beneficial effects of GSE on intestinal permeability, tight junction protein expression and assembly, inflammation and overall health using immunoblotting, qRT-PCR, histochemical, immunohistochemical and other biochemical and molecular approaches. We will also assess dynamic changes of gut microbiota due to dietary supplementations using quantitative PCR as well as pyrosequencing. In vitro cell cultures will be further conducted to elucidate underlying mechanisms.

Progress 02/01/13 to 09/30/17

Outputs
Target Audience:Commodity groups and scientific community Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?One undergraduate student,3 PhD students and 1 postdoc have been receiving training through this project. How have the results been disseminated to communities of interest?Peer-reviewed publications and meeting abstracts. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Intestinal epithelium forms the largest and critical barrier in our body, which is highly selective and fulfills diverse functions. Proper intestinal barrier is essential for health, which is maintained by a delicate balance of epithelial proliferation and differentiation. Adenosine monophosphate-activated protein kinase (AMPK) is a master regulator of energy metabolism and recently recognized for its important regulatory role in cell differentiation. We found that polyphenolic extracts from purple potato augmented AMPK activity and further enhanced intestinal differentiation in both human colonic epithelial Caco-2 cells and ex vivo cultured mouse gut. Knocking out AMPK using CRISPR/Cas9 system abolished the positive effects of purple potato extract on intestinal epithelial differentiation and barrier function. These data indicate that purple potato extract exerts protective effect on gut epithelium via activating AMPK.

Publications

  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Bibi, S., Y. Kang, M. Du, and M. J. Zhu. (2017). Dietary red raspberries attenuate dextran sulfate sodium-induced acute colitis. Journal of Nutritional Biochemistry, 51:40-46.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: L.F. de Sousa Moraes, X. Sun, M. C. G. Peluzio, and M. J. Zhu. (2017). Anthocyanins /anthocyanidins and colorectal cancer: what is behind the scenes? in press
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Sun, X., M. Du, D. A. Navarre and M. J. Zhu (2017). Purple potato extract promotes intestinal epithelial differentiation and barrier function by activating AMP-activated protein kinase. Molecular Nutrition and Food Research, in press
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Sun, X., Q. Y. Yang, C. J. Rogers, M. Du, and M. J. Zhu. (2017). AMPK regulate intestinal differentiation via histone modification of CDX2. Cell Death and Differentiation, 24: 819-831.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Wang, S., X. Liang, Q. Yang, X. Fu, M. J. Zhu, B.D. Rodgers, Q. Jiang, M. V. Dodson, and M. Du. (2017). Resveratrol enhances brown adipocyte formation and function by activating AMP-activated protein kinase (AMPK) ?1 in mice fed high-fat diet. Molecular Nutrition and Food Research, 61: 1600746.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Zou, T., Q. Yang, B. Wang, M. J. Zhu, P. W. Nathanielsz, and M. Du. (2017). Resveratrol supplementation to high fat diet-fed pregnant mice promotes brown and beige adipocyte development and prevents obesity in male offspring. Journal of Physiology, 595:1547-1562.


Progress 10/01/15 to 09/30/16

Outputs
Target Audience:Commodity groups and scientific community. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Three PhD students, Yansong Xue, Lina Sheng and Shima Bibi, and one MS student, Yifei Kang have been receiving training through this project How have the results been disseminated to communities of interest?Peer-reviewed publications and meeting abstracts. What do you plan to do during the next reporting period to accomplish the goals?In the next reporting period, we will be conducting studies exploring the beneficial effects of more dietary factors on gut epithelial health and underlying mechanisms.

Impacts
What was accomplished under these goals? Objective1: Determine the mechanisms by which dietary factors impacts human chronic diseases. Beyond their nutritional impact to colonic epithelial cells, the intestinal microbiota metabolite butyrate has been shown to exert beneficial effects on intestinal homeostasis and metabolism. Mast cells are well known for their roles in mediating allergy responses and regulating gut inflammation. We demonstrate that butyrate profoundly inhibited proliferation of mouse mastocytoma P815 cells through inducing cell cycle arrest and apoptosis, as well as decreasing c-Kit activation; butyrate also increased early and late stage apoptotic P815 cells. Additionally, butyrate suppressed Fc?RI-dependent cytokine production in murine primary BMMC, which are likely mediated by inhibition of histone deacetylation. Goji berry is a traditional Chinese tonic food. Dietary goji berry ameliorated DSS-induced body weight loss, diminished diarrhea and gross bleeding, resulted in a significantly decreased disease activity index, as well as DSS associated colon shortening. Histologically, it ameliorated mucosal damage and neutrophil infiltration into colonic intestinal tissue in response to DSS challenge, which was associated with decreased expression of chemokine (C-X-C motif) ligand 1 (CXCL1) and monocyte chemoattractant protein-1 (MCP-1), as well as inflammatory mediators, interleukin-¬6 and cyclooxygenase-2. In summary, Goji supplementation confers protective effects against DSS­induced colitis, which has the potential to be used as a complementary therapeutic approach for alleviating inflammatory bowel disease symptoms. Objective 4. Increase beneficial or decrease adverse effects of bioactive constituents and microbes in food. Treatment of E. coli O157:H7 infection is difficult since many antibiotics are shown to induce SOS response and enhance Stx production. Thus, an alternative antimicrobial intervention of E. coli O157:H7 in human infection is needed. Cinnamon is an antimicrobial spice that has been widely used for thousands of years. We found that Cinnamon oil not only effectively inhibited growth of E. coli O157:H7 at high concentration, but also dramatically reduced both Stx2 phage and total phage induction in E. coli O157:H7 at a sub-inhibitory concentration. The inhibitory effect might be due to the suppression of bacterial SOS response key regulator RecA and vital RNA polyadenylation enzymes (PNPase and PAP I). Additionally, C. cassia oil has bactericidal effects against bovine mastitis pathogenic isolates possibly through disruption of membrane structure. These data suggest its potential application as a therapeutic to control pathogenic bacterial infections.

Publications

  • Type: Journal Articles Status: Awaiting Publication Year Published: 2016 Citation: Wang, S., X. Liang, Q. Yang, X. Fu, M. J. Zhu, B.D. Rodgers, Q. Jiang, M. V. Dodson, and M. Du. (2017). Resveratrol enhances brown adipocyte formation and function by activating AMP-activated protein kinase (AMPK) ?1 in mice fed high-fat diet. Molecular Nutrition and Food Research, in press.
  • Type: Journal Articles Status: Awaiting Publication Year Published: 2016 Citation: Zou, T., Q. Yang, B. Wang, M. J. Zhu, P. W. Nathanielsz, and M. Du. (2017). Resveratrol supplementation to high fat diet-fed pregnant mice promotes brown and beige adipocyte development and prevents obesity in male offspring. Journal of Physiology, in press
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Xue, Y., S. Zhang, M. Du, and M. J. Zhu. (2017). Dandelion extract suppresses reactive oxidative species and inflammasome in intestinal epithelial cells. Journal of Functional Food, 29: 10-18.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Kang, Y., Y. Xue, M. Du., M. J. Zhu. (2016). Preventative effects of Goji berry in dextran sulfate sodium-induced colitis. Journal of Nutritional Biochemistry, 40: 70-76.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Xue, Y., H. Zhang, X. Sun, and M. J. Zhu. (2016). Metformin improves ileal epithelial barrier function in interleukin-10 deficient mice. PLoS ONE,11: e0168670
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Sheng, L., B. Rasco, and M. J. Zhu. (2016). Cinnamon oil inhibited Shiga toxin 2 phage induction and Shiga toxin 2 production in E. coli O157:H7. Applied Environmental Microbiology, 82: 6531-6540.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Sheng, L., S.A. Olsen, J. Hu, W. Yue, W. J. Means, and M. J. Zhu. (2016). Grape seed extract regulates virulence factors of CDC top-six non-O157 STEC through inhibiting quorum sensing. International Journal of Food Microbiology, 229: 24-32.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Zhu, H., M. Du, L. Fox, and M. J. Zhu. (2016). Bactericidal effects of Cinnamomum cassia oil against bovine mastitis bacterial pathogens. Food Control, 66: 291-299.


Progress 10/01/14 to 09/30/15

Outputs
Target Audience:Commodity groups and scientific community Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?A postdoc research associate, Dr. Shuming Zhang, two Ph.D. students, Yifei Kang and Shima Bibi, and one exchanging Ph. D. student, Hanying Zhang have been receiving training through this project. How have the results been disseminated to communities of interest?Peer-reviewed publications and meeting abstracts. What do you plan to do during the next reporting period to accomplish the goals?In the next reporting period, we will be conducting studies exploring mechanisms responsible for the beneficial effects of GSE and other food bioactive compounds.

Impacts
What was accomplished under these goals? Using interleukin-10 (Il10)-deficient mice, we found that 12 weeks of grade seed extract (GSE) supplementation improved jejunum health in interlukin10-deficient mice. GSE supplementation increased villus length, mucosal thickness and enhanced goblet cell density associated with enhanced expression of villin and two key differentiation transcription factors, Hairy/Enhancer of Split 1 (Hes1) and Krüppel-Like Factor-4 (KLF4), and increased p21 (CIP1/WAF1) content. Consistent with its anti-inflammatory effects, GSE supplementation decreased tumor necrosis factor a (TNF-a ) and interferon-? expression and down-regulated NF-?B signaling. Furthermore, GSE decreased total alkaline phosphatase activity with a concomitant increase in intestinal alkaline phosphatase protein. Data indicate that GSE improves jejunum health in interlukin10-deficient mice likely through suppressing inflammation and regulating alkaline phosphatase. Mast cell is known for its roles in mediating food allergy and regulating gut inflammation. Butyrate, a major short chain fatty acid produced by gut microbiota, exerts beneficial effects on intestinal homeostasis. Its production is enhanced by GSE and other plant origin bioactive. We demonstrated that butyrate profoundly inhibited proliferation of mouse mastocytoma P815 cells through inducing cell cycle arrest and apoptosis, as well as decreasing c-Kit activation. In murine bone marrow derived mast cells (BMMC), butyrate suppressed Fc?RI-dependent TNF-? and interleukin 6 (IL-6) release, which was associated with decreased mitogen-activated protein kinase extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and c-Jun N-terminal kinases (JNK) activation. In addition, butyrate treatment substantially enhanced histone 3 acetylation in both P815 and BMMC and decreased Fc?RI-dependent mRNA expression of tnf-a? and il-6 in BMMC, mimicking the effect of Trichostatin A, a known histone deacetylase inhibitor (HDACi). Chromatin immunoprecipitation further revealed that butyrate enhanced acetylation of the tnf-a? and il-6 promoter regions. These data show that butyrate regulating murine mast cell function likely mediated by HDAC inhibition, partially explaining the beneficial effects of GSE and other bioactive compounds in fruits on gut health.

Publications

  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Zhang, H., M. Du, Q. Yang, and M. J. Zhu. (2016). Butyrate suppresses murine mast cell proliferation and cytokine production through inhibiting histone deacetylase. Journal of Nutritional Biochemistry, 2016, 27: 299-306.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Bibi, S., Y. Kang, G. Yang, and M. J. Zhu. (2016). Grape seed extract improves small intestinal morphology through suppressing inflammation and regulating alkaline phosphatase in IL10-deficient mice. Journal of Functional Food, 20: 245-252.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Wang, S., M. J. Zhu, and M. Du. (2015). Prevention of obesity by dietary resveratrol: how strong is the evidence? Expert Review of Endocrinology and Metabolism, 39:967-976.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Zhang, S., and M. J. Zhu. (2015). Characterization of polyphenolics in grape pomace extracts using ESI Q-TOF MS/MS. HSOA Journal of Food Science and Nutrition, 2015, 1:001.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Yang, G., Y. Xue, H. Zhang, M. Du, and M. J. Zhu. (2015). Favorable effects of GSE on intestinal epithelial differentiation and barrier function in IL10-deficient mice. British Journal of Nutrition, 2015:1-9.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Wang, S., X. Liang, Q. Yang, X. Fu, C. Rogers, M. J. Zhu, B.D. Rodgers, Q. Jiang, M. Dodson, M. Du. (2015). : Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) a1. International Journal of Obesity, 39:967-976.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Zhu, M. J., S. A. Olsen, L. Sheng, Y. Xue, W. Yue. (2015). Antimicrobial efficacy of grape seed extract against Escherichia coli O157:H7 growth, motility and Shiga toxin production. Food Control, 51:177-182.


Progress 10/01/13 to 09/30/14

Outputs
Target Audience: Grape commission and scientific community Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Guan Yang, a M.S. student, received training through this project,and graduated successfully in Spring2014. In addition, a postdoc research associate, Dr. Shuming Zhang, and two Ph.D. students, Yifei Kang and Shima Bibi, have received training through this project. How have the results been disseminated to communities of interest? Peer-reviewed publications and meeting abstracts. What do you plan to do during the next reporting period to accomplish the goals? In the next reporting period, we will be conducting studies exploring mechanisms responsible for the beneficial effects of GSE and other food bioactive compounds.

Impacts
What was accomplished under these goals? Impairment of gut epithelial barrier function is a key predisposing factor for inflammatory bowel disease, type 1 diabetes (T1D) and related autoimmune diseases. We found that maternal obesity induced impaired glucose tolerance and lower serum insulin levels, inflammation and impaired gut barrier function in female offspring of nonobese diabetic (NOD) mice. Concomitantly, female offspring born to obese dams showed more severe islet lymphocyte infiltration (major manifestation of insulitis) in pancreas, suggesting the enhanced gut permeability in offspring of obese dams might predispose them to the development of T1D. On the other hand, using interleukin-10 (Il10)-deficient mice, we found that 12 weeks of GSE supplementation improved gut barrier function as indicated by decreased intestinal permeability and increased colonic goblet cells density and mucin mRNA expression. Immunohistochemical analyses revealed lower ß-catenin accumulation in the crypts of colon tissues of GSE supplemented mice, which was associated with decreased mRNA expression of two down-stream effectors of Wnt/catenin signaling, myelocytomatosis oncogene protein (Myc) and Cyclin D1(ccnd1). Consistently, GSE supplementation decreased the colonic proliferating cell nuclear antigen (PCNA) positive cells, a well-known cell proliferation marker, and a weakened extracellular-signal-regulated kinases (ERK1/2) signaling. Data indicate that GSE exerts its beneficial effects on Il10-deficient mice likely via inhibiting Wnt/ß-catenin pathway.

Publications

  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Wang, B., G. Yang, X. Liang, M. J. Zhu, and M. Du. (2014). Grape seed extract prevents skeletal muscle wasting in Interleukin 10 knockout mice. BMC Complementary and Alternative Medicine, 14:162-169.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Yang, G., H. Wang, Y. Kang, and M. J. Zhu. (2014). Grape seed extract improves epithelial structure and suppresses inflammation in the ileum of Il10-deficient Mice. Food and Function, 5: 2558-2563
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Zhu, M. J., S. A. Olsen, L. Sheng, Y. Xue, W. Yue. (2015). Antimicrobial efficacy of grape seed extract against Escherichia coli O157:H7 growth, motility and Shiga toxin production. Food Control, 51:177-182.
  • Type: Journal Articles Status: Awaiting Publication Year Published: 2014 Citation: Wang, S., X. Liang, Q. Yang, X. Fu, C. Rogers, M. J. Zhu, B.D. Rodgers, Q. Jiang, M. Dodson, M. Du. (2014). Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) a1. International Journal of Obesity.
  • Type: Journal Articles Status: Awaiting Publication Year Published: 2014 Citation: Zhang, S., and M. J. Zhu. (2014). Characterization of polyphenolics in grape pomace extracts with ESI Q-TOF MS/MS. Food Science and Nutrition
  • Type: Journal Articles Status: Other Year Published: 2014 Citation: Yang, G., Y. Xue, H. Zhang, M. Du, and M. J. Zhu. (2014). Favorable effects of GSE on intestinal epithelial differentiation and barrier function in IL10-deficient mice. British Journal of Nutrition, in revision.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Wang, H., Y. Xue, B. Wang, J. Zhao, X. Yan, Y. Huang, M. Du, and M. J. Zhu. (2014). Maternal obesity exacerbates insulitis and type I diabetes in NOD mice. Reproduction, 148:73-79.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Xue, Y., H. Wang, M. Du, and M. J. Zhu. (2014). Maternal obesity induces gut inflammation and impairs gut epithelial barrier function in NOD mice. Journal of Nutritional Biochemistry, 25: 758-764.
  • Type: Conference Papers and Presentations Status: Submitted Year Published: 2014 Citation: Bibi, S., Y. Kang, M. Du., M. J. Zhu. (2015). Grape seed extract enhances jejunum epithelial differentiation likely through suppressing inflammation in IL10-/- mice. Experimental Biology Meeting, Boston, Massachusetts, March28-April 1, 2015.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2014 Citation: Yang, G., Y. Xue, M. Du, B. Chew, and M. J. Zhu. (2014). GSE supplementation improves colonic cell differentiation via inhibiting Wnt/beta-catenin pathway in interleukin-10-deficient mice. The 2014 Institute of Food Technologists Annual Meeting, New Orleans, Louisiana, June 21-24, 2014
  • Type: Conference Papers and Presentations Status: Published Year Published: 2014 Citation: Xue, Y., H. Wang, M. Du, and M. J. Zhu. (2014). Maternal obesity induces gut inflammation and impairs gut epithelial barrier function in NOD mice. The 2014 Institute of Food Technologists Annual Meeting, New Orleans, Louisiana, June 21-24, 2014


Progress 02/01/13 to 09/30/13

Outputs
Target Audience: Grape commission and scientific community Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Hui Wang, a PhD student, and Serena Olson, a M.S. student, received training through funding of this project. Both of them have graduated successfully. How have the results been disseminated to communities of interest? Peer-reviewed publications and meeting abstracts. What do you plan to do during the next reporting period to accomplish the goals? In the next reporting period, we will be conducting studies exploring mechanisms responsible for the beneficial effects of GSE. We also plan to expand our studies to the health beneficial effects of other food bioactive compounds.

Impacts
What was accomplished under these goals? Inflammatory bowel disease (IBD) broadly refers to two major chronic intestinal disorders: Crohn’s disease (CD) and ulcerative disease (UC), both of which incur huge health costs in theU.S. and around the world. Though the etiology and pathogenesis of IBD remain poorly defined, the current understanding indicates that the pathogenesis of IBD might involve the defects in intestinal epithelial barrier. Up to now, pharmacological therapies for IBD long-term management rely on anti-inflammatory drugs, which can result in serious side effects, including secondary infections and immunosuppression. Thus alternative approaches or adjuvant therapies are needed, which can provide long-term management of the disease with a low-risk profile. Grape seed extract (GSE) is a by-product of the wine industry, with abundant polyphenolic compounds known for their anti-inflammatory and anti-oxidative effects, which exert a number of beneficial effects including prevention of cancer, cardiovascular diseases and diabetes. However, no study has been done regarding trophic effects of GSE on colitis symptom using interleukin (IL)-10-deficient mice, a commonly used animal model for studying human chronic IBD. The objective of this project was to evaluate the protective effects of GSE on IBD symptom and to further explore the underlying mechanisms using IL10-deficient mice. Six-week-old C57BL/6 wi1d-type (WT) mice and IL10-deficient mice (IL10KO) were assigned to a standard rodent diet (CON) or a diet supplemented with grape seed extract (GSE, 1% of dry feed weight) for 16 weeks. Dietary GSE supplementation did not affect food intake and body weight gain among treatments. GSE supplementation ameliorated IBD disease indices in IL10KO mice. To further explore mechanisms responsible for the observed beneficial effects of GSE on disease indices of IL10KO mice, we analyzed gut epithelial barrier function, a primary pre-disposing factor for the incidence of IBD, type 1 diabetes and other autoimmune diseases. We found that the colonic goblet cell density of IL10KO mice was numerically lower than that of WT mice, while GSE supplementation increased goblet cell density in both WT and IL10KO mice. Consistently, claudin2, a pore forming tight junction protein, were reduced in both GSE fed WT and IL10KO mice. Compared to WT-CON mice, GSE supplementation also minimized the splenomegaly in IL10KO mice. Concomitantly, GSE supplementation attenuated inflammation and neutrophil infiltration in IL10KO mice. Furthermore, GSE supplementation increased the abundance of Lactobacilli and Bacteroides in gut microbiota of IL10KO mice. In conclusion, results demonstrated that dietary GSE supplementation exerts protective effects in IBD indices of IL10KO mice through multiple mechanisms.

Publications

  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Wang, H., Y. Xue, H. Zhang, Y. Huang, G Yang, M. Du, and M. J. Zhu. (2013). Dietary grape seed extract ameliorates symptoms of inflammatory bowel disease in interleukin-10 deficient mice. Molecular Nutrition & Food Research, 57:2253-2257.
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2013 Citation: Olsen, S., J. Hu, Y. Xue, and M. J. Zhu. (2013). Effects of grape seed extract on the growth of top six non-O157 Shiga toxin producing Escherichia coli. The 2013 International Association for Food Protection Annual Meeting, Charlotte, North Carolina, July 28-31, 2013
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2013 Citation: Olsen, S.A., J. Hu, W.J. Means, R.J. McCormick, M. J. Zhu. (2012). Effects of grape seed extract on the growth and Shiga toxin production of Escherichia coli O157:H7. 112th General Meeting of the American Society for Microbiology, San Francisco, California, June 16-19, 2012