Source: PENNSYLVANIA STATE UNIVERSITY submitted to NRP
REGULATION OF IMMUNE FUNCTION AND GASTROINTESTINAL HOMEOSTASIS BY NUTRIENTS: ESPECIALLY VITAMIN D.
Sponsoring Institution
State Agricultural Experiment Station
Project Status
COMPLETE
Funding Source
STATE
Reporting Frequency
Annual
Accession No.
0228668
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
Apr 1, 2012
Project End Date
Mar 31, 2017
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
PENNSYLVANIA STATE UNIVERSITY
208 MUELLER LABORATORY
UNIVERSITY PARK,PA 16802
Performing Department
Veterinary & Biomedical Sciences
Non Technical Summary
Dietary recommendations for patients with chronic gastrointestinal diseases like inflammatory bowel disease (IBD) are largely based on avoidance of large groups of food that are associated with the worsening of symptoms. This avoidance is extremely difficult to maintain over time and leads to multiple micronutrient and sometimes macronutrient deficiencies. Understanding the mechanisms by which individual nutrients alter key microorganisms involved in exacerbating or modulating symptoms would allow us to identify a larger variety of foods and nutrients that can reshape the microbiota to improve symptoms in patients with chronic gastrointestinal diseases. The possibility that simple supplementation with a nutrient like vitamin D could improve immune function would be a low cost benefit of interest in treating animals and humans. This research will have national and international impact. The findings from the proposed experiments will have an impact on controlling immune responses of humans and animals worldwide.
Animal Health Component
(N/A)
Research Effort Categories
Basic
(N/A)
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
7023450109070%
7023450110010%
7021470109010%
7021470110010%
Knowledge Area
702 - Requirements and Function of Nutrients and Other Food Components;

Subject Of Investigation
1470 - Mushrooms and other edible fungi; 3450 - Milk;

Field Of Science
1090 - Immunology; 1100 - Bacteriology;
Goals / Objectives
Nutrients regulate immune function and gastrointestinal homeostasis. In particular, vitamin D deficiency is more common in people who have inflammatory bowel disease (IBD). The incidence of IBD is highest in North America and Northern Europe places where sunlight is lower especially in the winter. Vitamin D is manufactured in the skin on exposure to sunlight and sunlight driven vitamin D synthesis is the major source of vitamin D for most people, since there are few foods that are naturally rich in vitamin D. Mice genetically engineered to spontaneously develop the symptoms of IBD were also made vitamin D deficient at birth. The mice were then either maintained deficient or given vitamin D supplements in their food to bring them up to the normal levels. The vitamin D deficient mice rapidly developed symptoms of IBD, which eventually resulted in the death of the mice. The supplemented mice developed milder IBD symptoms and didn't die. T cells and other immune cells have vitamin D receptors and are vitamin D targets. In addition, vitamin D and other nutrients alter the composition of the gastrointestinal microflora affects diseases like IBD. The proposal described here will further probe the link between vitamin D status and IBD. We have determined that vitamin D does regulate experimental IBD and by several different mechanisms. We plan to continue study mechanisms that explain vitamin D inhibition of IBD and to expand the work to include other nutrients. In addition, we have expanded the work from mice to humans to look at the effects of vitamin D on the human immune system. A better understanding of the mechanisms underlying the relationship between vitamin D status and IBD may lead to improved therapies and interventions for patients with IBD. The research proposed in this project is significant because it will provide such knowledge
Project Methods
Mice lacking the VDR, or the enzyme that converts pre-vitamin D to active 1,25(OH)2D3 (Cyp27B1), or wildtype (WT) mice or WT mice treated with 1,25(OH)2D3 will be compared for the type of T cell responses generated to prototypical immunization protocols that generate Th1 or Th2 immune responses. The Cyp27B1 KO mice will be vitamin D deficient unless they are fed preformed 1,25(OH)2D3. This will be assessed by immunizing animals with the model antigen ovalbumin complexed with complete freunds adjuvant, which generates preferential Th1 responses, or complexed with Alum, which generates preferential Th2 responses. Following immunization and boost, T cells from these mice will be analyzed for cytokine production, as an indication of the magnitude and types of T cell response generated. We hypothesize that T cells lacking VDR or the Cyp27B1 will generate altered T cell responses compared to WT mice. These experiments will determine if we can manipulate T cell immune responses by manipulating the amount of vitamin D. Mice lacking the VDR or Cyp27B1 enzyme, or WT mice treated with 1,25(OH)2D3 or WT mice fed diets that contain differing amounts of nutrients (vitamin D, vitamin A, lactose, mushrooms) will be compared for the susceptibility to the induction of inflammation in the gut using dextran sodium sulfate or a bacterial infection with Citrobacter rodentium. Following challenge; the mice will be analyzed for the expression of surface markers and cytokines consistent with regulation of inflammation. In addition we will generate bone marrow chimeras using VDR, Cyp27B1 and WT mice fed different nutrients as donors and recipients. In this way we can determine if the defects are hematopoetic derived or due to the defects in the gut environment. We hypothesize that both the gut and the hematopoetic cells of deficient mice will have altered responses to challenges of the gastrointestinal tract. We plan to determine the underlying causes of these differences. Mice fed different nutrients (vitamin D, vitamin A, lactose, mushrooms) will have the composition of the gastrointestinal microflora characterized. Changes in the composition of the gut microflora will be assessed by sequencing, and analysis of the urinary metabolites. These changes will be compared to the immunological and disease outcomes in 2. Mice lacking the VDR or Cyp27B1 enzyme, or WT mice will be compared for T development. Populations of cells studied will include the major components of the thymus double positive and double negative CD4/CD8 cells and minor components NKT cells, regulatory T cells etc. In addition, the function of these cell types will be determined as a function of age and not only the maturation in the thymus but circulation to the periphery as well. We expect that different T cell populations will develop in the presence versus the absence of vitamin D and the function of the cells will also depend on the presence of the VDR and adequate 1,25(OH)2D3. The in vivo effects of vitamin D on iNKT cells will be probed in animal models of multiple sclerosis.

Progress 04/01/12 to 03/31/17

Outputs
Target Audience:The general population in Pennsylvania is the target audience and in particular individuals with immunemediated disease and gastrointestinal infections. Served during this year were patients with food born infectious disease, inflammatory bowel disease, asthma, and multiple sclerosis. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?The work has supported training for 12 graduate students, 7 undergraduate students, 2 post-doctoral fellow, 1 technician and many collaborators. Those individuals are as follows, graduate students: Stephanie Bora, Lindsey Snyder, Yan-Ding Lin, Jamaal Jones, Luming Zhao, Micha Davila, Ming Xu, Elly Song and Pingyun Lyu, technician: Veronika Weaver, post-doctoral fellows: Yuan Tian, and Wei-Bei Wang, undergraduate students: Pratiti Roy, Kevin Diehl, Takara Richard, Valerie Pascoe, Jasmine Sun, Amy Ye, Tia Walker. Two graduate students (Bora and Snyder) partially supported on USDA national needs grant #2914-38420-21822 (Perdew PI). Other collaborators on the work included Andrew Patterson, Sandeep Prabhu, Istvan Albert, Catharine Ross and Gary Perdew at the Pennsylvania State University. How have the results been disseminated to communities of interest?The information gained has been disseminated to the public through the scientific literature but also by speaking engagements to physicians and other health professionals at National and International conferences and more informally via e-mail or phone contact directly with the public. What do you plan to do during the next reporting period to accomplish the goals?We will continue to investigate the mechanisms by which vitamin D, vitamin A, edible mushrooms, selenium and diet control gastrointestinal health. We will continue to work on projects that look at the effects of homing receptors on the mucosal architecture. We have submitted several new grants. Dr. Cantorna and Dr. Xiong will continue to deliver lectures on the work to various stakeholders that translate and emphasize the impact of the work. The new efforts will be part of a new project

Impacts
What was accomplished under these goals? We continue to make good progress identifying the mechanisms by which vitamin D, vitamin A and other nutrients regulate gastrointestinal immunity and homeostasis. Our work has expanded to determine the tragets of nutrient on the microbiota. We have done extensive metabolomics and microbiome studies and have determined that the microbiota regulate vitamin D metabolism. We have recently completed our mushroom study and have submitted two new grant applications one on vitamin A and one on edible mushrooms. We received a supplement to our NIH funded vitamin D project to determine the effect of sex as a variable in those experiments. We also received a post-doctoral fellowship from the American Association of Immunologists to support Dr. Tian. In addition, we also received three NIH grants to study mechanisms regulating establishment and function of resident innate immune cells in the skin.

Publications

  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Cantorna M.T. 2017. "Diet-derived short chain fatty acids stimulate intestinal epithelial cells to induce mucosal tolerogenic dendritic cells" J Immunol. 198:4188
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: James, J. V. Weaver, and M.T. Cantorna. 2017 Control of circulating IgE by the vitamin D receptor in vivo involves B cell intrinsic and extrinsic mechanisms. J. Immunol. 198:1164-1171.
  • Type: Journal Articles Status: Accepted Year Published: 2017 Citation: Y. Tian, Nicols, R G, J. Cai, A.D. Patterson and M.T. Cantorna. 2017 Vitamin A deficiency in mice alters host and gut microbial leading to altered energy homeostasis. In press: J. Nutr Biochem
  • Type: Theses/Dissertations Status: Published Year Published: 2017 Citation: Jamall James, 2016. The effects of vitamin D on B cells and IgE, The Pennsylvania State University


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

Outputs
Target Audience:The general population in Pennsylvania is the target audience and in particular individuals with immune-mediated disease and gastrointestinal infections. Served during this year were patients with food born infectious disease, inflammatory bowel disease, asthma, and multiple sclerosis. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?The work has supported training for 7 graduate students, 6 undergraduate students, 1 post-doctoral fellow, 1 technician and many collaborators. Those individuals are as follows, graduate students: Sarah Sumner, Jazmyn Nichele Stewart, Stephanie Bora, Lindsey Snyder, Yan-Ding Lin, Kaitlin McDaniel and Jamaal Jones, technician: Veronika Weaver, post-doctoral fellow: Yuan Tian, undergraduate students: Michael White, William Eckroft, Pratiti Roy, Kevin Diehl, Takara Richard and Elaine Santiago. Other collaborators on the work included Andrew Patterson, Sandeep Prabhu, Istvan Albert, Catharine Ross and Gary Perdew at the Pennsylvania State University. How have the results been disseminated to communities of interest?The information gained has been disseminated to the public through the scientific literature but also by speaking engagements to physicians and other health professionals at National and International conferences and more informally via e-mail or phone contact directly with the public. What do you plan to do during the next reporting period to accomplish the goals?We will continue to investigate the mechanisms by which vitamin D, vitamin A, edible mushrooms, selenium and diet control gastrointestinal health. We are submitting several grants for support from the National Institutes of Health and the Crohn's and Colitis Foundation of America. Dr. Cantorna will continue to deliver lectures on the work to various stakeholders that translate and emphasize the impact of the work.

Impacts
What was accomplished under these goals? We continue to make good progress identifying the mechanisms by which vitamin D, vitamin A and other nutrients regulate gastrointestinal immunity and homeostasis. Our work has expanded to determine the targets of nutrient on the microbiota. Recently we have determined that the microbiota regulate vitamin D status. We have recently renewed our vitamin D funding for an additional 5 years and continue to have funds for the study of vitamin A and edible mushrooms as regulators of gastrointestinal homeostasis.

Publications

  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Cantorna, M. T. IBD: Vitamin D and IBD: moving towards clinical trials. Nat Rev Gastroenterol Hepatol. doi: 10.1038/nrgastro.2016.72.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Cantorna, M.T. 2016. Commentary Vitamin D and Lung Infection. Infect Immun doi: 10.1128/IAI.00679-16.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Waddell A, Zhao J, Cantorna M.T. 2015. Natural killer T cells can help mediate the protective effects of 1,25-dihydroxyvitamin D3 in experimental autoimmune encephalomyelitis in mice. Int Immunol. 27:237-244.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Bora, S., and Cantorna, M.T. 2016 The role of UVR and vitamin D on T cells and inflammatory bowel disease. Photochem Photobiol Sci doi: 10.1039/C6PP00266H
  • Type: Theses/Dissertations Status: Published Year Published: 2016 Citation: Jamaal L. James, 2016. The regulation of immunoglobulin E responses requires the vitamin D receptor, The Pennsylvania State University.
  • Type: Theses/Dissertations Status: Published Year Published: 2015 Citation: Kaitlin McDaniel, 2015. The effects of vitamin A deficiency on host defense during Citrobacter rodentium infection, The Pennsylvania State University.


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

Outputs
Target Audience:The general population in Pennsylvania is the target audience and, in particular, individuals with immune-mediated diseases. Served during this year were pregnant women, patients with inflammatory bowel disease, asthma, chronic obstructive pulmonary disease, and multiple sclerosis. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?The work has supported training for eight graduate students, six undergraduate students, one post-doctoral fellow, one technician and many collaborators. Those individuals are as follows, graduate students: James Fraser, Stephanie Bora, Kaitlen McDaniel, Lindsey Snyder, Yang-Ding Lin, Brenita Jenkins, Jamaal Jones, and Jing Chen; technician: Veronika Weaver; postdoctoral fellow: Amanda Waddell; undergraduate students: Michael White, Prattit Roy, Kelly Smith, William Eckroth, and Elaine Santiago. Other collaborators at Penn State on included: Allison Gernand, Troy Ott, Francisco Diaz, Andrew Patterson, Sandeep Prabhu, Istvan Albert, Catharine Ross and Gary Perdew. How have the results been disseminated to communities of interest?The information gained has been disseminated to the public through the scientific literature, and by speaking engagements to physicians and other health professionals at national and international conferences, and more informally via e-mail or phone contact directly with the public. What do you plan to do during the next reporting period to accomplish the goals?We will continue to investigate the mechanisms by which vitamin D, vitamin A, edible mushrooms, selenium and diet control gastrointestinal health. We are submitting several grants for support from the National Institutes of Health (NIH). Dr. Cantorna will continue to deliver lectures on this work to various stakeholders whotranslate and emphasize the impact of the work.

Impacts
What was accomplished under these goals? We continue to make good progress identifying the mechanisms by which vitamin D and other nutrients regulate gastrointestinal homeostasis. Vitamin D regulates homeostasis in the gut by regulating host immune function and the microbiota. Recently, we have determined that the microbiota regulate vitamin D status. We have two new funded projects that look at the mechanisms of how other nutrients (vitamin A and edible mushrooms) regulate gastrointestinal homeostasis.

Publications

  • Type: Journal Articles Status: Published Year Published: 2015 Citation: McDaniel, K. L., Restori, K. H., Dodds, J. W., Kennett, M. J., and Cantorna, M. T. Vitamin A deficient hosts become nonsymptomatic reservoirs of Escherichia coli-like infections. Inf. Immun. 2015 Jul;83(7):2984-2991.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Cantorna, M. T., Snyder, L., Lin, Y.D., and Yang, L. Vitamin D and 1,25(OH)2D regulation of T cells. Nutrients. 2015 Apr 22;7(4):3011-30121.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Cantorna, M. T., McDaniel, K., Bora, S., Chen, J., and James, J. Vitamin D, immune regulation, the microbiota and inflammatory bowel disease. Exp. Biol. Med. 2014 Nov;239(11):1524-1530.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Chen, J., Waddell, A., Lin, Y. D., and Cantorna, M. T. Dysbiosis caused by vitamin D receptor deficiency confers colonization resistance to Citrobacter rodentium through modulation of innate lymphoid cells. Mucosal Immunol. 2015 May; 8(3):618-626.
  • Type: Theses/Dissertations Status: Published Year Published: 2014 Citation: Chen J. 2014. The role of vitamin D in maintaining gastrointestinal homeostasis. The Pennsylvania State University.


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

Outputs
Target Audience: The general population in Pennsylvania is the target audience and in particular individuals with immune-mediated disease. Served during this year were pregnant women, patients with inflammatory bowel disease, asthma, chronic obstructive pulmonary disease and multiple sclerosis. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? The work has supported training for nine graduate students, five undergraduate students, two post-doctoral fellows, 1 technician and many collaborators. Those individuals are as follows: graduate students James Fraser, Stephanie Bora, Kaitlen McDaniel, Lindsey Snyder, Yan-Ding Lin, Brenita Jenkins, Jamaal Jones, Jing Chen, and Jot Hui Ooi; technician: Veronika Weaver; post-doctoral fellows Linlin Yang and Amanda Waddell; and undergraduate students Michael White, Nathan Vasquez, Kelly Smith, Kristen Leader, Kara Scherer. Other collaborators on this work included: Avery August, Terryl Hartman, and Jill Smith, previously at the Pennsylvania State University; and Allison Gernand, Troy Ott, Francisco Diaz, Andrew Patterson, Sandeep Prabhu, Istvan Albert, Catherine Ross and Gary Perdew, currently at the Pennsylvania State University. How have the results been disseminated to communities of interest? The information gained has been disseminated to the public not only through the scientific literature, but also via speaking engagements to physicians and other health professionals at National and International conferences, and more informally via e-mail or phone contact directly with the public. What do you plan to do during the next reporting period to accomplish the goals? We will continue to investigate the mechanisms by which vitamin D, vitamin A, edible mushrooms, selenium and diet control gastrointestinal health. We are submitting several grants for support from the National Institutes of Health. Dr. Cantorna will continue to deliver lectures on the work to various stakeholders that translate and emphasize the impact of the work.

Impacts
What was accomplished under these goals? We have continued to identify new mechanisms by which nutrients regulate the microbiota in the gut, immune cells and how these changes affect health and susceptibility to diseases primarily of the gastrointestinal tract. We have extended our work to look at specific mechanisms by which nutrients, especially vitamin D, control of infections in the gastrointestinal tract. We have started a new collaborative effort that aims to understand how vitamin D control of the microbiota and immunity impacts pregnancy outcomes. We have published 10 manuscripts: six on vitamin D, one on vitamin A, one on mushrooms, one on diet, and one on selenium. Most of the work continues to give new insight into the use of nutrients, especially vitamin D, to maintain gastrointestinal homeostasis.

Publications

  • Type: Journal Articles Status: Awaiting Publication Year Published: 2014 Citation: Chen J., A. Waddell, Y. Lin, and M.T. Cantorna 2014 Innate lymphoid cell driven dysbiosis and colonization resistance to Citrobacter rodentium in vitamin D receptor knockout mice. Mucosal Immunol. (In Press).
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Kaushal, N., A.K. Kudva, A.D. Patterson, C. Chiaro, M.J. Kennett, D. Desai, S. Amin, B.A. Carlson, M.T. Cantorna and K.S. Prabhu. 2014. Crucial role of macrophage selenoproteins in experimental colitis. J. Immunol. 193:3683-3692.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: He X., J. Yan, X. Zhu, Q. Wang, W. Pang, Z. Qi , M. Wang, E. Luo , D. M. Parker, M.T. Cantorna, L. Cui, Y. Cao. 2014. Vitamin D inhibits the occurrence of experimental cerebral malaria in mice by suppressing the host inflammatory response. J Immunol. 193:1314-1323.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Feeney M.J., J. Dwyer , C. M. Hasler-Lewis, J. A. Milner, M. Noakes , S. Rowe , M. Wach, R.B. Beelman, J. Caldwell , M.T. Cantorna, L.A. Castlebury, S.T. Chang, L.J. Cheskin, R. Clemens, G. Drescher, V.L. Fulgoni 3rd, D.B. Haytowitz, V.S. Hubbard, D. Law , A. Myrdal Miller, B. Minor, S.S. Percival, G. Riscuta, B. Schneeman, S. Thornsbury, C.D. Toner, C.E. Woteki, D. Wu. 2014. Mushrooms and health summit proceedings. J. Nutr. 144:1128S-1136S.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Cantorna M.T., A.Waddell. 2014. The vitamin D receptor turns off chronically activated T cells. Ann. N. Y. Acad. Sci. 1317:70-75.
  • Type: Journal Articles Status: Awaiting Publication Year Published: 2014 Citation: Cantorna M.T., K. McDaniel, S. Bora, J. Chen, J. James. 2014. Vitamin D, immune regulation, the microbiota and inflammatory bowel disease. Exp. Biol. Med. (In Press).
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Chen J., D. Bruce D, M.T. Cantorna. 2014. Vitamin D receptor expression controls proliferation of na�ve CD8+ T cells and development of CD8 mediated gastrointestinal inflammation. BMC Immunol. 15:6.
  • Type: Websites Status: Published Year Published: 2014 Citation: Ooi, J.H., A. Waddell, Y. Lin, I. Albert, L.T. Rust, V. Holden, and M.T. Cantorna. 2014. Dominant effects of the diet on the microbiome and the local and systemic immunse response in mice. Plos One 9:e86366.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Restori, K.H., K.L. McDaniel, A.E. Wray, M.T. Cantorna, and A.C. Ross. 2014. Streptococcus pneumoniae-Induced Pneumonia and Citrobacter rodentium-Induced Gut Infection Differentially Alter Vitamin A Concentrations in the Lung and Liver of Mice. J Nutr. 144:392-398.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Ooi, J.H., K.L. McDaniel, V. Weaver and M.T. Cantorna. 2014. Murine CD8+ T cells but not macrophages express the vitamin D 1?-hydroxylase. J. Nutr. Biochem. 25:58-65.


Progress 10/01/12 to 09/30/13

Outputs
Target Audience: The general population in Pennsylvania is the target audience and, in particular, individuals with immune-mediated disease. Served during this year were patients with inflammatory bowel disease, asthma, chronic obstructive pulmonary disease and multiple sclerosis. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? The work has supported training for nine graduate students, five undergraduate students, two post-doctoral fellows, two technicians and many collaborators. Graduate students include Stephanie Bora, Kaitlen McDaniel, Lindsey Snyder, YanDing Lin, Brenita Jenkins, Jamaal Jones, Jyotika Varshney, Jing Chen, and Jot Hui Ooi. Technicians include Veronika Weaver and Rhonda Smith. Post-doctoral fellows include Linlin Yang and Amanda Waddell. Undergraduates include Amanda Gregor, Lauren Applegate, Kelly Smith, Kristen Leader, and Kara Scherer. Other collaborators on the work included Avery August, Terryl Hartman, and Jill Smith, previously at the Pennsylvania State University; and Eric Harvill, Andrew Patterson, Sandeep Prabhu, Istvan Albert, Catherine Ross, Gary Perdew and Bhushan Jayarao, who are from Pennsylvania State University. How have the results been disseminated to communities of interest? The information gained has been disseminated to the public through scientific literature, by speaking engagements to physicians and other health professionals at National and International conferences, and more informally, via e-mail or phone contact directly with the public. What do you plan to do during the next reporting period to accomplish the goals? We will continue to investigate the mechanisms by which vitamin D, vitamin A, edible mushrooms and diet control gastrointestinal health. We are submitting several grants for support from the National Institutes of Health (NIH). Dr. Cantorna will continue to deliver lectures on the work to various stakeholders that translate and emphasize the impact of the work.

Impacts
What was accomplished under these goals? We have shown that vitamin D, mushrooms and other nutrients are critical for the maintenance of a healthy gastrointestinal tract. The immune system is effected by these nutrients, which shape the way it responds to danger signals. We have also shown that some of the diet works, in part, by changing the gastrointestinal microbiome. Our data further suggest that other changes in vitamin D, edible mushrooms and vitamin A result in changes in the bacterial microflora. Changes in the microbiome affect the health of the gut, therefore the changes in diet impact the health of the mice. Changes as a result of vitamin D can be seen in the gut, but also at distant sites like the central nervous system or lung. This group has focused on understanding how these nutrients help control a gastrointestinal infection. We have published two papers based on our investigation into effects of nutrients in humans. We have also published a manuscript on vitamin D and another one on edible mushroom as controllers of the microbiome and gastrointestinal health.

Publications

  • Type: Journal Articles Status: Awaiting Publication Year Published: 2013 Citation: J. H. Ooi, J. Li, C.J. Rogers, and M.T. Cantorna. 2013. Vitamin D regulates the gut microbiome and protects mice from dextran sodium sulfate-induced colitis. J. Nutr. In press.
  • Type: Journal Articles Status: Awaiting Publication Year Published: 2013 Citation: M. Pinkerton, V.Chinchilli, E. Banta, T. Craig, A. August, R. Bascom, M.T. Cantorna, E. Harvill, and F.T. Ishmael. 2013. Differential expression of microRNAs in exhaled breath condensates of patients with asthma, patients with chronic obstructive pulmonary disease, and healthy adults. J. Allergy Clin. Immunol. In press.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: L. Yang, V. Weaver, J.P.Smith, S. Bingaman, T. J. Hartman, and M.T. Cantorna. 2013. Therapeutic effect of vitamin D supplementation in a pilot study of Crohns patients. Clin Transl Gastroenterol. 4:e33.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: J. Varshney, J.H. Ooi, B.M. Jayarao, I. Albert, J. Fisher, R.L. Smith, A.D. Patterson and M.T. Cantorna. 2013. White button mushrooms increase microbial diversity and accelerate the resolution of Citrobacter rodentium infection in mice. J. Nutr 143:526-532.


Progress 10/01/11 to 09/30/12

Outputs
OUTPUTS: Nutrients regulate immune function and gastrointestinal homeostasis. In particular, vitamin D deficiency is more common in people who have inflammatory bowel disease (IBD). Mice genetically engineered to spontaneously develop the symptoms of IBD were also made vitamin D deficient at birth. Diet affects the development of immune mediated diseases including IBD. We have made progress on all of our primary objectives. We have determined that vitamin D controls T cell proliferation, and by regulating the bacterial microflora. In addition, we have determined that other nutrients (mushrooms, vitamin A, and lactose) affect the development of IBD. Regulation of these mechanisms accounts for the difference between health and diseases of the gastrointestinal tract. The information gained has been disseminated to the public through the scientific literature but also by speaking engagements to physicians and other health professionals at National and International conferences and more informally via e-mail or phone contact directly with the public. PARTICIPANTS: Dr. Cantorna was the principal investigator on the project and supervised 7 graduate students, 5 undergraduate students, 2 post-doctoral fellow, 2 technicians and many collaborators. Those individuals are as follows, graduate students: Stephanie Bora, Kaitlen McDaniel, Jun Zhao, Jamaal Jones, Jyotika Varshney, Jing Chen, and Jot Hui Ooi, technicians: Veronika Weaver and Rhonda Smith, post-doctoral fellow Linlin Yang and Amanda Waddell, undergraduates: Amanda Gregor, Lauren Applegate, Gabriele Innes, Michelle Wilke, and Abby Urraro. Other collaborators on the work included Avery August previously at the Pennsylvania State University (now at Cornell), Eric Harvill, Andrew Patterson, Terryl Hartman, Jill Smith, Sandeep Prabhu, Istvan Albert, Catherine Ross, Timothy Craig and Bhushan Jayarao at the Pennsylvania State University and Hector DeLuca from the University of Wisconsin, Madison. TARGET AUDIENCES: The general population in Pennsylvania is the target audience and in particular individuals with immune-mediated disease. Served during this year were patients with inflammatory bowel disease, asthma, chronic obstructive pulmonary disease and multiple sclerosis. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
The dietary information available to the general public especially on vitamin D is not based in science. It is important to determine the mechanisms by which nutrients and vitamin D function so that accurate messages can be made to the public. The present dietary recommendations for patients with bowel disease are largely based on avoidance of large food groups and the slow re-introduction of some foods when disease symptoms subside. A better understanding of the mechanisms underlying the relationship between nutrition and disease may lead to improved therapies and interventions for patients with immune-mediated diseases including multiple sclerosis, asthma, chronic obstructive pulmonary disease and inflammatory bowel disease. The information learned is also relevant to animal species that often suffer from idiopathic colitis that might be resolved by a change in diet.

Publications

  • Zhao, J. 2012. Regulatory Role of NKT Cells on Effects of 1,25(OH)2D3 in Mice with Experimental Autoimmune Encephalomyelitis. M.S. Thesis. The Pennsylvania State University, University Park, PA. 28 pp.
  • Varshney, J. 2012 The Beneficial Effects of White Button Mushrooms on the Gut Health. M.S. Thesis. The Pennsylvania State University, University Park, PA. 52 pp.
  • Ooi, J. H. and M. T. Cantorna. 2012. Vitamin D Mediated Inhibition of Helicobacter Species Protects Mice from Colitis. The Journal of Immunology 188:51.7.