Source: PURDUE UNIVERSITY submitted to NRP
ANTI-INFLAMMATORY AND ANTI-OXIDANT EFFECTS OF POTATO ANTHOCYANINS -- ROLE OF GUT BACTERIA
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
AFRI COMPETITIVE GRANT
Reporting Frequency
Annual
Accession No.
1018496
Grant No.
2016-67017-29285
Cumulative Award Amt.
$307,108.00
Proposal No.
2018-09143
Multistate No.
(N/A)
Project Start Date
Nov 1, 2018
Project End Date
Oct 31, 2021
Grant Year
2019
Program Code
[A1341]- Food Safety, Nutrition, and Health: Function and Efficacy of Nutrients
Recipient Organization
PURDUE UNIVERSITY
(N/A)
WEST LAFAYETTE,IN 47907
Performing Department
Food Science
Non Technical Summary
The prevalence of Inflammatory Bowel Disease (IBD) in the US is on the rise with 1.5 million IBD patients. Experimental evidence suggests that dietary anthocyanins can reduce inflammation and oxidative stress, two critical factors in the pathogenesis of IBD. In the US, there is a growing interest for color-fleshed potatoes that can serve as an important delivery vehicle for dietary anthocyanins. Although dietary anthocyanins have a poor bioavailability, they may still affect gut inflammation due to direct contact and metabolism in the gut. However, the interaction between anthocyanins and gut microbiota in exerting anti-inflammatory properties in the gut remains somewhat elusive. In this proposal we propose to determine (1) the extent to which white-, purple- and red-fleshed potatoes suppress gut inflammation and oxidative stress in acute and chronic models of murine colitis, (2) the ability of gut bacterial metabolites formed from color-fleshed potatoes to suppress inflammation using conventional and germ-free mice, and (3) the extent to which color-fleshed potato diets alter inflammatory potential of the gut microbiota. This project, if successful, will delineate the interaction between gut bacteria and anthocyanin and provide mechanistic data to support the anti- inflammatory role of color-fleshed potato anthocyanins in reducing colitis. It might also improve the economic value of the crop because of the health functionality.
Animal Health Component
50%
Research Effort Categories
Basic
50%
Applied
50%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
7011310101020%
7011310200020%
7013840116040%
7013840115020%
Knowledge Area
701 - Nutrient Composition of Food;

Subject Of Investigation
1310 - Potato; 3840 - Laboratory animals;

Field Of Science
1160 - Pathology; 1010 - Nutrition and metabolism; 2000 - Chemistry; 1150 - Toxicology;
Goals / Objectives
The overall goal of this proposal is to determine the extent to which bioactive gut bacterial metabolites of white-, and colorfleshed potatoes, alter the inflammatory potential of gut bacteria and suppress colonic inflammation in acute and chronic models of murine colitis.Objectives:1. Determine the role of gut bacterial metabolism in anti-inflammatory potential of color-fleshed potatoes using conventional and germ-free mice2. Define the extent to which color-fleshed potato diets alter inflammatory potential of the gut microbiota.
Project Methods
We will be using acute dextran sodium sulfate (DSS) colitis (C57BL/6 mice) and chronic colitis mice models. We will also be using germ free mice to determine the role of gut microbiota on the anti-inflammatory properties of potato supplementation. Histopathology, Enzyme linked Immunosorbent Assay, q-PCR and HPLC methods will be employed to assess the gut pathology and inflammation and oxidative stress. Metabolite profiling will be done using MS QTof. Abundance of microbiota will be assessed using 16S rRNA sequencing analysis. Inflammatory potential of the gut bacteria will be assessed by in vitro culture assays.

Progress 11/01/18 to 10/31/21

Outputs
Target Audience:Stakeholders, scientists, graduate and undergraduate students, extension educators, farmers, consumers, industry personnel Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Allowed to train and mentor Postdoc, graduate and undergraduate students in the area of plant foods, bioactive compounds, inflammation, gut bacteria and gut health. Students and the mentor could participate in the American Society of Nutrition conference. The PI could give an invited talk in the ACS symposium and develop collaborations with other researchers. The preliminary data from this grant helped to secure another USDA foundation grant and also other internal grants. The grant also played a critical role in fostering international collaborations and training visiting scientists. How have the results been disseminated to communities of interest?The results were presented in seminars, symposiums, USDA W4002 annual meeting, and the Gordon research conference. The attendees represent scientists, graduate and undergraduate students in nutrition, food science, chemistry and plant science. We published two review articles and several research articles on anti-inflammatory properties of color-fleshed potatoes What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? The overall goal of this proposal is to determine the extent to which bioactive gut bacterial metabolites of white-, and color-fleshed potatoes suppress colonic inflammation in acute and chronic models of murine colitis. We have shown that color-fleshed potatoes suppress colonic inflammation in mice and ameliorate DSS-induced colitis. The anti-colitic effects differ based on the type of predominant anthocyanin and are dependent on the gut bacteria. Objective 1: Determine the role of gut bacterial metabolism in the anti-inflammatory potential of color-fleshed potatoes using conventional and germ-free mice. To determine the role of gut bacteria in the anti-colitic effects of color-fleshed potatoes we conducted animal experiments using both conventional and microbiota-ablated mice. Our results suggest that the anti-colitic effects of potatoes are partly dependent on gut bacteria. We completed all analyses and the manuscript has been published in a reputed international journal. We also completed the experiment with germ-free mice to further verify the role of bacteria in the anti-colitic effects of color-fleshed potatoes because antibiotics used in microbiota ablated mice might interfere with the inflammation induced by DSS. Our findings indicated that except for the gut permeability, other parameters were not improved by the consumption of potatoes, which is consistent with the results observed in microbiota-ablated mice. Objective 2: Define the extent to which color-fleshed potato diets alter the inflammatory potential of the gut microbiota. Anthocyanin-containing purple potatoes have the potential to suppress the bacterial dysbiosis induced by DSS treatment, reduce colonic inflammation and maintain gut health by decreasing the relative abundance of specific pathogenic bacteria such as Enterobacteriaceae, Escherichia coli and pks+ E. coli, reducing the increased flagellin levels induced by DSS treatment, and increasing the abundance of beneficial bacteria Akkermansia muciniphila. These results indicate that the purple-fleshed potatoes can suppress the DSS-induced increase in the inflammatory potential of gut bacteria.

Publications

  • Type: Journal Articles Status: Published Year Published: 2021 Citation: Mummidi S, Farook VS, Reddivari L, Hernandez-Ruiz J, Diaz-Badillo A, Fowler SP, Resendez, RG, Akhtar F, Lehman DM, Jenkinson CP, Arya R, Lynch JL, Canas J, DeFronzo RA, Hale DE, Blangero J, Lopez-Alvarenga JC, Duggirala R, Vanamala J. 2021. Serum carotenoids and pediatric metabolic index predict insulin sensitivity in Mexican American children. Sci. Rep 11(1), 1-11
  • Type: Conference Papers and Presentations Status: Published Year Published: 2021 Citation: Li S*, Reddivari L. 2021. Improvement of Gut Barrier Function by Potato Anthocyanins Is Dependent on Gut Microbiota. Curr Develop Nutr 5 (Suppl_2): 344
  • Type: Conference Papers and Presentations Status: Published Year Published: 2021 Citation: Fu W*, Reddivari L. 2021. Complexation With Polysaccharides Enhanced Polyphenol Gastrointestinal Stability and Activity. Curr Develop Nutr 5 (Suppl_2): 314
  • Type: Journal Articles Status: Published Year Published: 2021 Citation: Li S, Wang T, Fu W, Kennett M, Cox AD, Lee D, Vanamala JKP, Reddivari L*. 2021. Role of gut microbiota in the anti-colitic effects of anthocyanin-containing potatoes. Mol Nutr Food Res 2100152 (selected for cover page)
  • Type: Journal Articles Status: Published Year Published: 2021 Citation: Wu B, Chang H, Chopra S, Reddivari L*. 2021. Characterization of maize near-isogenic lines with enhanced flavonoid expression to be used as tools in diet-health complexity. Front Plant Sci 11, 2249
  • Type: Journal Articles Status: Published Year Published: 2021 Citation: Li S, Wang T, Fu W, Wu B, Xu B, Pamuru, R, Kennett M, Vanamala JKP, Reddivari L*. 2021. Anthocyanin-containing purple potatoes ameliorate DSS-induced colitis in mice. J Nutr Biochem 93:108616


Progress 11/01/19 to 10/31/20

Outputs
Target Audience:Scientists, graduate and undergraduate studnets and consumers Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Participation in American Society for Nutrition conference and Whistler center seminar series How have the results been disseminated to communities of interest?The results were presented in seminars, webinars and conferences. The attendees represent scientists, graduate and undergraduate students in nutrition, food science, chemistry and plant science. What do you plan to do during the next reporting period to accomplish the goals?We will analyze the importance of gut bacterial metabolism in the anti-inflammatory properties of potato anthocyanins using germ-free mice and the extent to which color-fleshed potatoes can reduce the inflammatory potential of gut bacteria.

Impacts
What was accomplished under these goals? Objective 1: Determine the role of gut bacterial metabolism in the anti-inflammatory potential of color-fleshed potatoes using conventional and germ-free mice. We completed animal experiments using both conventional and microbiota ablated mice to understand the role of bacteria in the anti-colitic effects of color-fleshed potatoes. Our results suggests that the anti-colitic effects of potatoes are in partly dependent on the gut bacteria. We completed all analyses and the manuscript is in preparation. We were not able to start the final experiment using germ-free mice because of the closure of the university during the pandemic. We started the experiments late and are almost at completion. Objective 2: Define the extent to which color-fleshed potato diets alter the inflammatory potential of the gut microbiota. Again due to pandemic we were not able to complete the experimenton time - but we are currently working on the analyses

Publications

  • Type: Journal Articles Status: Published Year Published: 2020 Citation: Wu B, Bhatnagar RS, Indukuri V, Chopra S3, March K3, Cordero N, Chopra S, Reddivari L. 2020. Intestinal mucosal barrier function restoration in mice by maize diet containing enriched flavan-4-ols. Nutrients. 12(4):896
  • Type: Journal Articles Status: Published Year Published: 2020 Citation: Cladis DP, Li S, Reddivari L, Cox A, Ferruzzi MG, Weaver CM. 2020. A 90-day oral toxicity study of blueberry polyphenols in ovariectomized Sprague-Dawley rats. Food Chem Toxicol. 139:111254
  • Type: Journal Articles Status: Published Year Published: 2020 Citation: Bao Y, Reddivari L, Huang JY. 2020. Novel cold plasma-assisted extraction for phenolic compounds from tomato pomace. Innov Food Sci Emerg Technol 65, 102445
  • Type: Journal Articles Status: Published Year Published: 2020 Citation: Bao Y, Reddivari L, Huang JY. 2020. Enhancement of phenolic compounds extraction from grape pomace by high voltage atmospheric cold plasma. LWT 133, 109970
  • Type: Conference Papers and Presentations Status: Published Year Published: 2020 Citation: Reddivari L, Li S, Wang T, Kennett M, Vanamala JKP. 2020. Role of Gut Microbiota in Anti-Colitic Effects of Color-Fleshed Potatoes. ASN annual meeting, Curr Develop Nutr 4 (Suppl_2): 460
  • Type: Conference Papers and Presentations Status: Published Year Published: 2020 Citation: Li S, Wang T, Xu B, Indukuri V, Vanamala JKP, Reddivari L. 2020. Anthocyanin-Containing Purple Potatoes Ameliorate DSS-Induced Colitis in Mice. ASN annual meeting, Curr Develop Nutr 4 (Suppl_2): 426
  • Type: Conference Papers and Presentations Status: Published Year Published: 2020 Citation: Wu B, Li S, Chang H, Anderson R, Chopra S, Reddivari L. 2020. Maize flavan-4-ols and anthocyanins alleviated dextran sulfate sodium-induced colitis in mice via intestinal barrier function restoration. ASN annual meeting, Curr Develop Nutr 4 (Suppl_2): 488
  • Type: Conference Papers and Presentations Status: Published Year Published: 2020 Citation: Wu B, Chang H, Chopra S, Reddivari L. 2020. Enhanced flavan-4-ols corn diet protects intestinal barrier function in mice. 62nd Annual Maize Genetics Meeting, March 12-15, Kailua-Kona, Hawaii.


Progress 11/01/18 to 10/31/19

Outputs
Target Audience:Scientists, graduate and undergraduate students and consumers Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Participation in Gordon research conference, Whistler Center seminar series and gut microbiome symposium How have the results been disseminated to communities of interest?The results were presented in seminars, symposiums, USDA W4002 annual meeting, and the Gordon research conference. The attendees represent scientists, graduate and undergraduate students in nutrition, food science, chemistry and plant science. We published two review articles and submitted two research articles on anti-inflammatory properties of color-fleshed potatoes What do you plan to do during the next reporting period to accomplish the goals?We will analyze the extent to which color-fleshed potatoes can reduce the inflammatory potential of gut bacteria using the fecal samples collected from both conventional and microbiota ablated mice

Impacts
What was accomplished under these goals? Objective 1: Determine the role of gut bacterial metabolism in the anti-inflammatory potential of color-fleshed potatoes using conventional and germ-free mice. We completed animal experiments using both conventional and microbiota ablated mice to understand the role of microbiota in the anti-inflammatory potential of color-fleshed potatoes. Administration of antibiotics resulted in a 95% reduction in gut bacterial load after eight weeks as measured by relative amplification of 16S using qPCR. Antibiotic-treated mice had five times greater cecum weight, a hallmark of germ-free mice, compared to no antibiotic mice irrespective of the treatment. Purple-fleshed potato supplementation suppressed (p ≤ 0.05) DSS-induced reduction in colon length and gut barrier function and the increase in IL-6 and IL-1β (p ≤ 0.05) compared to control diet in mice with intact microbiota. Potato diets did not suppress DSS-induced colitic like symptoms in antibiotic mice indicating the critical role of gut bacteria in the anti-inflammatory potential of anthocyanin-containing potatoes. Objective 2: Define the extent to which color-fleshed potato diets alter the inflammatory potential of the gut microbiota. Fecal samples from both conventional and microbiota-ablated mice were collected, and the extracts were prepared and archived at -80oC. Cell culture protocols are optimized to measure the anti-inflammatory potential.

Publications

  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Li S, Wang T, Reddivari L. Purple-fleshed potato anthocyanins attenuate DSS-induced colitis in an intestinal microbiota dependent manner. Natural Products and Bioactive Compounds, Gordon Research Conference, July 28  August 2, 2019, Andover, NH
  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Reddivari L*. Anthocyanin anti-inflammatory properties  Role of gut bacteria. The multistate research project Nutrient Bioavailability  Phytonutrients and Beyond W4002 Meeting annual meeting. February 7-8, 2019, Davis, CA
  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Bowen KJ*, Kris-Etherton PM, Reddivari L. Effects of diets that vary in fatty acid composition on fecal short-chain fatty acid levels and their relationship with circulating lipids and lipoproteins, American Heart Association Epi/Lifestyle 2019 meeting
  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Indukuri V*, Mason M, Reddivari L, lambert J, Vanamala J. Anti-inflammatory Effect of Table Grapes in Apc(Min/+) Mouse Model of Intestinal Tumorigenesis. Experimental Biology, April 6-9, 2019, Orlando, FL
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Radcliffe JS, Brito LF, Reddivari L, Schmidt M, Herman EM, and Schinckel AP. 2019. A swine model of soy protein-induced food allergy: implications in human and swine nutrition. Animal Frontiers. 9:52-59
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Li S, Wu B, Fu W, and Reddivari L. 2019. The anti-inflammatory effects of dietary anthocyanins against ulcerative colitis. Int J Mol Sci. 20:2588.
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Reddivari L, Wang T, Wu B, and Li S. 2018. Potato: An anti-inflammatory food?. Am J Potato Res: 96(2):164-169.