Source: WASHINGTON STATE UNIVERSITY submitted to
PIGMENTED POTATO RESTORES GUT EPITHELIAL HEALTH IMPAIRED BY OBESITY
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
AFRI COMPETITIVE GRANT
Reporting Frequency
Annual
Accession No.
1014924
Grant No.
2018-67017-27517
Project No.
WNP03129
Proposal No.
2017-06996
Multistate No.
(N/A)
Program Code
A1341
Project Start Date
Mar 1, 2018
Project End Date
Feb 28, 2023
Grant Year
2018
Project Director
Zhu, M.
Recipient Organization
WASHINGTON STATE UNIVERSITY
240 FRENCH ADMINISTRATION BLDG
PULLMAN,WA 99164-0001
Performing Department
School of Food Science
Non Technical Summary
Obesity is a worldwide epidemic and is associated with serious health problems. The latter include impairment of gut barrier function, or "leaky gut", which is responsible for a number of diseases including gut inflammatory diseases and food allergies. Thus, there is an urgency to improve gut barrier function impaired due to obesity. Dietary polyphenols are known for their potent beneficial effects on health including gut epithelial health despite poorly defined mechanisms. As a staple food, potatoes can be an excellent source of dietary polyphenols. While white potatoes contain a modest amount of polyphenols, pigmented potatoes have high levels of chlorogenic acid and anthocyanins, both of which activate AMP-activated protein kinase (AMPK). We hypothesize that polyphenols of pigmented potato improve intestinal epithelial integrity and barrier function impaired by obesity via activating AMPK and associated signaling. We will use a whole food approach by feeding potatoes with different polyphenol contents to obese mice, in conjunction with genetically modified mouse and in vitro cell cultures for mechanistic exploration. The knowledge gained from these studies will promote the consumption of potato, benefiting a critical industry in Northwest. In addition, such knowledge can lead to novel dietary guidelines to prevent or mitigate gut health problems associated with obesity, thus generating large societal impacts.
Animal Health Component
100%
Research Effort Categories
Basic
70%
Applied
30%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
7021310101050%
7021310102030%
7021310103020%
Knowledge Area
702 - Requirements and Function of Nutrients and Other Food Components;

Subject Of Investigation
1310 - Potato;

Field Of Science
1030 - Cellular biology; 1010 - Nutrition and metabolism; 1020 - Physiology;
Goals / Objectives
Obesity affects more than one-third of the US population and is known to induce inflammation and impair intestinal epithelial development. Gut epithelium forms the largest, most critical and highly selective barrier in our body. Disturbances of intestinal barrier function allow the transmission of macromolecules and bacteria across the epithelial barrier, inducing inflammation and abnormal immune responses, which in turn further disrupt gut epithelial integrity and barrier function, forming a vicious cycle. Thus, it is vital to develop strategies that can protect or re-establish gut barrier function; however, our understanding of molecular mechanisms linking diet to epithelial barrier function remains rudimentary. Polyphenols are a large heterogeneous group of compounds occurring in plant foods, known for their preventive or therapeutic effects on metabolic diseases including obesity. Potatoes are one of the most widely consumed staple foods in the U.S. Pigmented potato contains high levels of both chlorogenic acid (CGA) and anthocyanins; however their relative contribution to gut epithelial health is unclear. AMP-activated protein kinase (AMPK) is as a master regulator of energy metabolism. Our preliminary studies showed that AMPK regulates intestinal epithelial cell differentiation and barrier function. These studies imply that AMPK may be a key mediator for the beneficial effects of potato polyphenols on gut epithelium. Our central hypothesis is that polyphenols of pigmented potato improve intestinal epithelial integrity impaired by obesity via activating AMPK and associated signaling. To test our central hypothesis, we will pursue two interrelated aims:Aim 1. Determine the impact of potato polyphenols on AMPK activation and gut epithelial development impaired due to obesity.Aim 2. Evaluate the mediatory role of AMPK in linking potato polyphenols to gut epithelial development and integrity.
Project Methods
Aim 1. Determine the impact of potato polyphenols on AMPK activation and gut epithelial development impaired due to obesity. We will use our unique potato cultivars, a white potato with low polyphenols, a pigmented potato (Purple Pelisse) rich in CGA and anthocyanins, and its corresponding CGA deficient potato. The diet-induced obesity mice model will be used in this study. This model mimics the typical Western diet and is very relevant to obesity in humans. Male C57BL/6J mice will be randomized to receive control diet (D12450J, Research Diets) with 10% energy from fat (CON) or an obesogenic diet (D12492, Research Diets) with 60% energy (OBE) for two months to develop obesity. Then, mice in the obesogenic group will be further separated into four treatments. As a result, there are five treatments: 1) Con diet without potato; 2) OBE without potato; 3) OBE+10% white potato; 4) OBE+10% purple potato; and 5) OBE+10% CGA deficient purple potato. Ten mice per dietary group will be used. Dietary potato treatments will last for 10 weeks. To avoid the potentially confounding effects of sex, only male mice will be used in the study. Fecal samples will be collected for gut microbiota pyrosequencing to comprehensively examine overall changes of gut microbiota. The intestinal barrier function will be measured using fluorescein isothiocyanate (FITC)-labeled dextran. Gut structure will also be analyzed by histological and immunohitochemical analysis. The phosphorylation of AMPK and related signaling pathways associated with epithelial renewal and differentiation will be further assessed. We expect that obesity will result in impaired epithelial cell differentiation and migration, and defective gut barrier function, which will be mitigated by dietary pigmented potatoes supplementation. In addition, we expect that CGA and anthocyanins in pigmented potato act together to activate AMPK and exert beneficial effects on epithelial health.Aim 2. Examine the mediatory role of AMPK in linking potato polyphenols to gut epithelial development and integrity. We will use epithelial cell cultures and AMPK conditional knockout mice to test the regulatory role of AMPK in linking potato polyphenols and gut epithelial health. Human colonic epithelial Caco-2 cells transfected with EGFP (CON), AMPK constant active (AMPKα WT) or AMPKα dominant negative constructs (K45R) will be treated with different amounts of Purple Pelisse polyphenol extract. The protein and mRNA level of intestinal epithelial differentiation markers and transcription factors and barrier functions will be analyzed. We expect that the promoting effects of polyphenols on epithelial differentiation will be blunted in AMPK deficient cells, demonstrating a mediatory role of AMPK. In addition, we plan to knockout AMPK specifically in intestinal epithelial cells using a double transgenic mice obtained by crossing AMPK floxed mice with Lgr5-Cre mice. Lgr5 is an exclusive marker of the intestinal epithelial stem cells. We expect that purple potato is effective in improving gut health in AMPK normal mice, but not in AMPK KO mice, showing the necessity of AMPK in mediating the beneficial effects of potato.

Progress 03/01/18 to 02/28/23

Outputs
Target Audience:The scientific community and commodity groups Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?This project has been providing training opportunities for three PhD students and one postdoc. Additionally, it offers training to one undergraduate student, allowing them to gain valuable on-hand experience. How have the results been disseminated to communities of interest?Peer-reviewed publications, meeting abstracts and presentations. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Maintaining a healthy intestinal barrier is crucial for overall health, relying on a delicate balance of epithelial proliferation and differentiation. Disruptions in gut epithelial barrier function can lead to inflammation and various health issues originating from the gut. Purple potatoes are rich in beneficial polyphenolic compounds, and the content and bioactivities of these extractable polyphenols are largely preserved during cooking processes. Our study demonstrated that purple potato extract (PPE) enhanced transepithelial electrical resistance and reduced paracellular FITC-dextran flux, and promoted intestinal epithelial differentiation in both cell cultures and ex vivo gut models. Moreover, PPE treatment activated AMP-activated Protein Kinase (AMPK) and upregulated the expression of CDX2, a key transcription factor regulating intestinal epithelial differentiation. Importantly, the positive effects of PPE on intestinal epithelial differentiation and barrier function were dependent on AMPK, as evidenced by their abolishment when AMPK was knocked out using the CRISPR/Cas9 system. These findings highlight the potential of PPE to improve gut epithelial differentiation and barrier function, with AMPK playing a crucial role in mediating these effects. The potential benefits of incorporating dietary purple potatoes for gut health were further investigated in vivo. Our studies revealed that including purple potatoes in the diet of interleukin-10-deficient mice improved gut structure, increased goblet cell abundance, and alleviated inflammation and colitis symptoms. Additionally, dietary supplementation with purple potatoes showed promising results in ameliorating the disease activity index in mice treated with dextran sulfate sodium (DSS). It reversed colonic structure loss, mucosal damage, and macrophage infiltration, while restoring the levels of tight junction proteins and CDX2 in DSS-treated mice. These positive effects were associated with the activation of AMPK and its downstream target, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) signaling pathways. PGC-1α is a core transcriptional coactivator involved in mitochondrial biogenesis. Consistently, purple potato supplementation enhanced mitochondrial oxidative phosphorylation, proteostasis, and protein-folding capacity. To further explore the potential mechanisms, the role of PGC-1α in purple potato polyphenol-induced intestinal differentiation was investigated using human colonic epithelial cells (Caco-2) in vitro. Consistent with findings from the mouse study, purple potato extract (PPE) upregulated the expression of PGC-1α, mitochondrial biogenesis-related enzymes, and the number of mitochondrial DNA copies. It also enhanced oxidative phosphorylation. Inhibition of PGC-1α using either the PGC-1α inhibitor or siRNA-mediated knockdown abolished the enhancing effects of PPE on the expression of differentiation markers and mitochondrial biogenesis. These results suggest that the AMPK/PGC-1α axis plays a critical role in mediating the beneficial effects of PPE on intestinal epithelial differentiation. Metabolic dysregulation has been increasingly recognized as a contributing factor in the development of intestinal inflammatory diseases and other metabolic disorders. Intestinal epithelial cells exhibit high metabolic activity and play a crucial role in maintaining the anaerobic environment of the gut lumen, which influences microbial homeostasis and dysbiosis. Hence, we investigated the potential benefits of alpha-ketoglutarate (aKG) supplementation on gut health. Alpha-ketoglutarate, an intermediate of the Krebs cycle, serves as a significant energy source for the epithelial cells lining the gastrointestinal tract. Our results revealed that aKG supplementation suppressed inflammation and the Wnt signaling pathway. It also improved epithelial structure and promoted the polarization of M1 to M2 macrophages. These effects were associated with strengthened intestinal barrier function and a transition from glycolytic to oxidative metabolism. To gain further insights into the underlying metabolic changes, we further conduct metabolomics analysis utilizing GC-MS. The results showed distinct separation between the control and aKG-supplemented groups in terms of gut metabolites. Pathway analysis revealed that the urea cycle was the most significantly affected pathway in response to aKG supplementation. Specifically, the aKG-supplemented group exhibited lower levels of urea, a known factor impairing intestinal barrier function, as well as reduced levels of ornithine, an intermediate of the urea cycle. These findings suggest that aKG supplementation could be a potential therapeutic approach for metabolic and inflammatory conditions affecting the gut. The gut microbiota plays a critical role in maintaining intestinal health and is increasingly recognized as a key factor contributing to the development of various gastrointestinal conditions. In this context, we sought to investigate the potential modulatory effects of dietary purple potato on the gut microbiota using an interleukin-10-deficient mouse model. Our study demonstrated that dietary supplementation with purple potato led to restoration of gut microbiota dysbiosis in interleukin-10-deficient mice in addition to the significant improvements in gut epithelial health. Specifically, purple potato intake resulted in a favorable shift in bacterial communities, characterized by a reduction in colitis-associated bacterial phyla such as Proteobacteria and Deferribacteres, and an increase in beneficial bacterial phyla including Firmicutes and Tenericutes. Furthermore, purple potato supplementation effectively reduced the abundance of bacterial families commonly elevated in colitis patients, such as Bacteroidaceae, Sutterellaceae, Coriobacteriaceae, Enterobacteriaceae, and Peptostreptococcaceae, while promoting the growth of beneficial bacterial families including Bifidobacteriaceae, Porphyromonadaceae, and Lachnospiraceae-Ruminococcaceae, which are known to produce the important microbial metabolite butyrate. Butyrate has been recognized for its beneficial effects on intestinal epithelial health. Consistently, our study revealed that butyrate treatment in Caco2 cells resulted in the suppression of proliferation, potentiation of differentiation, and induction of apoptosis. These effects were mediated through the enhancement of α-ketoglutarate-dependent DNA demethylation of mismatch repair genes. Overall, our findings highlight the close relationship between dietary polyphenols, the AMPK/PGC-1α axis, gut microbiota, microbial metabolites, and epigenetic modifications, all of which are intricately associated with intestinal health. This research sheds light on the potential of dietary interventions, such as purple potato supplementation, for modulating the gut microbiota and promoting intestinal epithelial health.

Publications

  • Type: Journal Articles Status: Published Year Published: 2022 Citation: Bravo-Iniguez, A. Q. Tian, M. Du and M. J. Zhu. 2022. Alpha-ketoglutarate promotes goblet cell differentiation and alters urea cycle metabolites in DSS-induced colitis mice. Nutrients, Nutrients, 14: 1148.
  • Type: Journal Articles Status: Published Year Published: 2022 Citation: Sun, Q., A. Bravo-Iniguez, Q. Tian, M. Du, and M. J. Zhu. 2022. PGC-1? is indispensable in purple potato extract-promoted intestinal epithelial differentiation and mitochondrial biogenesis. Journal of Functional Food, 98: 109291.
  • Type: Journal Articles Status: Published Year Published: 2022 Citation: Tian, Q., Z. Xu, Q. Sun, A. Bravo Iniguez, M. Du, and M. J. Zhu. 2022. Broccoli-derived glucoraphanin activates AMPK/PGC1?/NRF2 pathway and ameliorates dextran-sulphate-sodium-induced colitis in mice. Antioxidants, 11: 2404.
  • Type: Journal Articles Status: Published Year Published: 2022 Citation: Wang, H., Q. Tian, M. Du, and M. J. Zhu. 2023. Metabolomic profiling for the preventive effects of dietary grape pomace against colorectal cancer. Journal of Nutritional Biochemistry, 116: 109308.
  • Type: Journal Articles Status: Submitted Year Published: 2023 Citation: Zhu, M. J., Q. Sun, S. Bibi, Y. He, Y. Xue, D. A. Navarre, and M. Du. 2023. Dietary purple potato modulates gut microbiota and alleviates colitis in IL-10-deficient mice. Submitted.
  • Type: Journal Articles Status: Submitted Year Published: 2023 Citation: Sun, Q., B. Shima, Y. Xue, M. Du, B. Chew, and M. J. Zhu. 2023. Dietary purple potato facilitates intestinal oxidative phosphorylation and suppresses mitochondrial unfolded protein response in DSS-induced colitis mice. Submitted.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2022 Citation: Sun, Q., A. Bravo-Iniguez, Q. Tian, M. Du, and M. J. Zhu. 2022. PGC-1? is indispensable in purple potato promoted intestinal epithelial differentiation and mitochondrial biogenesis. Current Developments in Nutrition, 6 (Suppl 1): 537
  • Type: Conference Papers and Presentations Status: Published Year Published: 2022 Citation: Bravo-Iniguez, A., Q. Tian, M. Du, and M. J. Zhu. 2022. Alpha-ketoglutarate promotes goblet cell differentiation and alters metabolome in a mouse model of colitis. FASEB J, 36 (Suppl 1): https://faseb.onlinelibrary.wiley.com/doi/10.1096/fasebj.2022.36.S1.R5000
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2023 Citation: Zhu, M. J., S. Bibi, Y. He, D. A. Navarre, and M. Du. Dietary purple potato intake restores gut microbiota in interleukin 10-deficient mice. American Society for Nutrition Annual Meeting, Boston, MA, July 22-25, 2023.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2023 Citation: Sun, Q., S. Bibi, Y. Xue, M. Du, and M. J. Zhu. Dietary purple potato mediates intestinal oxidative phosphorylation and mitochondrial unfolded protein response in DSS-induced colitis mice. American Physiology Summit, Long Beach, CA. April 20-23, 2023.


Progress 03/01/21 to 02/28/22

Outputs
Target Audience:The scientific community and commodity groups Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Three Ph.D. students had been receiving training through this project. This project also provides training opportunities for one undergraduate student. How have the results been disseminated to communities of interest?Peer-reviewed publications, meeting abstracts and presentations. What do you plan to do during the next reporting period to accomplish the goals?We will be continuing our research efforts on studying the beneficial effects of purple potatoes on gut health and exploring underlying mechanisms.

Impacts
What was accomplished under these goals? Perturbation of gut epithelial barrier function is a central pathogenic factor for gut inflammation and associated disorders, which are becoming common due to intake of western high fat diet and the prevalence of obesity. We previously reported that polyphenol-rich purple potato extract enhances intestinal epithelial differentiation and improves gut barrier function, which reduces gut inflammation associated with a high-fat diet. Furthermore, the content, anti-inflammatory activity, and other bioactivities of extractable polyphenols from purple potatoes subjected to different cooking processes were largely retained. Intestinal epithelial cells are continuously renewed, which depends on a delicate balance between proliferation and differentiation of intestinal stem cells. The differentiation of gut epithelial cells requires extensive mitochondrial biogenesis to meet the energy demands needed for nutrient absorption and endocrine functions. Mitochondrial biogenesis is tightly regulated by a core transcriptional coactivator, peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α, which is known to be impaired by high-fat diet intake or obesity. We found that purple potato polyphenols enhancing intestinal differentiation is mediated by AMP-activated protein kinase (AMPK). AMPK activated PGC-1a and stimulated mitochondrial biogenesis. Thus, we further evaluated the effects of purple potato polyphenol supplementation on mitochondrial biogenesis as well as the potential role of PGC-1α in purple potato polyphenol-induced intestinal differentiation. Correlated with enhanced differentiation and AMPK activation, purple potato polyphenols up-regulated the level of PGC-1α, the expression of mitochondrial biogenesis-related enzymes, and the number of mitochondrial DNA copies. Consistently, purple potato polyphenols enhanced the intracellular contents of citrate and malate, which are the key intermediates in the tricarboxylic acid cycle and are representatives of metabolic flux and oxidative phosphorylation in mitochondria. However, inhibition of PGC-1α by either PGC-1α inhibitor SR-18292 or siRNA-mediated knockdown eliminated the enhancing effects of PP extract on the expression of differentiation markers and mitochondrial biogenesis. Data showed that the AMPK/PGC-1α axis plays a critical role in purple potato polyphenol-enhanced intestinal epithelial differentiation.

Publications

  • Type: Journal Articles Status: Under Review Year Published: 2022 Citation: Sun, Q., A. Bravo-Iniguez, Q. Tian, M. Du, and M. J. Zhu. 2022. PGC-1? is indispensable in purple potato extract-promoted intestinal epithelial differentiation and mitochondrial biogenesis.
  • Type: Journal Articles Status: Accepted Year Published: 2022 Citation: Bravo-Iniguez, A. Q. Tian, M. Du and M. J. Zhu. 2022. Alpha-ketoglutarate promotes goblet cell differentiation and alters urea cycle metabolites in DSS-induced colitis mice. Nutrients, accepted.
  • Type: Journal Articles Status: Published Year Published: 2021 Citation: Sun, Q., M. Du, D. A. Navarre, and M. J. Zhu. 2021. Cooking methods on the bioactivity of polyphenols in purple potatoes. Antioxidants, 10: 1176
  • Type: Journal Articles Status: Published Year Published: 2021 Citation: Tian, Q., A. Bravo-Iniguez, Q. Sun, H. Wang, M. Du and M. J. Zhu. 2021. Dietary alpha-ketoglutarate suppressed dextran sulfate sodium induced colitis associated glycolytic metabolism. Molecular Nutrition and Food Research. 65: 2000936
  • Type: Journal Articles Status: Published Year Published: 2021 Citation: Bravo Iniguez, A., and M. J. Zhu. 2021. Hop bioactive compounds in prevention of nutrition-related noncommunicable diseases. Critical Reviews in Food Science and Nutrition, 61: 1900-1913
  • Type: Conference Papers and Presentations Status: Published Year Published: 2021 Citation: Bibi, S., Y. Xue, Y. He, M. Du, B. Chew, D. A. Navarre, and M. J. Zhu. 2021. Dietary purple potato supplementation ameliorates gut inflammation and associated colitis. American Nutrition Society Annual Meeting, Virtual, June 7-10, 2021.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2021 Citation: Sun, Q., D. A. Navarre, M. Du, and M. J. Zhu. 2021. Cooking methods on extractability and bioactivity of polyphenolic compounds in purple potatoes. American Nutrition Society Annual Meeting, Virtual, June 7-10, 2021.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2021 Citation: Wang, H., Q. Tian, Z. Xu, A. B. Iniguez, M. Du, and M. J. Zhu. 2021. Metabolomic profiling for the preventive effects of dietary grape pomace against colorectal cancer. American Nutrition Society Annual Meeting, Virtual, June 7-10, 2021.


Progress 03/01/20 to 02/28/21

Outputs
Target Audience:Scientific community and commodity groups Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Three PhD students had been receiving training through this project. This project also provides training opportunities for a visiting professor and one undergraduate student. How have the results been disseminated to communities of interest?Peer-reviewed publications, meeting abstracts and presentations. What do you plan to do during the next reporting period to accomplish the goals?We will be continuing our research efforts on studying the beneficial effects of purple potatoes on gut health and exploring underlying mechanisms.

Impacts
What was accomplished under these goals? Perturbation of gut epithelial barrier function is a central pathogenic factor for gut inflammation and associated disorders, which are becoming common due to intake of western high fat diet and the prevalence of obesity. Purple potatoes contain a high level of beneficial polyphenolic compounds, which are hypothesized to have anti-obesity effects through improving gut barrier function, suppressing inflammation, and preventing dysbiosis. We previously reported that polyphenol-rich purple potato extract enhances intestinal epithelial differentiation and improves gut barrier function, which reduces gut inflammation associated with a high-fat diet. We further found that AMP-activated protein kinase has a mediatory role. In mice, dietary purple potatoes ameliorated inflammation and symptoms of colitis in interleukin-10-deficient mice associated with the improved gut structure and goblet cell abundance. Gut microbiota is recognized as a crucial factor contributing to inflammatory intestinal disease. Associated with improved gut epithelial health, dietary purple potato supplementation restored gut microbiota dysbiosis in interleukin-10-deficient mice. Specifically, purple potato supplementation increased Firmicutes, a predominant phylum in gut microbiota, and bloomed Bifidobacteriaceae, Porphyromonadaceae, and Lachnospiraceae-Ruminococcaceae family, both of which are decreased in individuals with intestinal inflammatory disease and colitis. Metabolic dysregulation has been increasingly implicated in the incidence of intestinal inflammatory disease. Intestinal epithelial cells have a very high metabolic rate and control the anaerobic state of the intestinal lumen, which in turn contributes to microbial homeostasis and dysbiosis. Alpha-ketoglutarate, as an intermediate of the Krebs cycle, is a significant source of energy for epithelial cells of the gastrointestinal tract. We found that alpha-KG supplementation suppressed inflammation and the Wnt signaling pathway, improved epithelial structure, and enhanced M1 to M2 macrophage polarization, which was associated with strengthened intestinal barrier function and enhanced glycolytic to oxidative metabolic transition.

Publications

  • Type: Journal Articles Status: Published Year Published: 2021 Citation: Tian, Q., A. Bravo-Iniguez, Q. Sun, H. Wang, M. Du and M. J. Zhu. 2021. Dietary alpha-ketoglutarate suppressed dextran sulfate sodium induced colitis associated glycolytic metabolism. Molecular Nutrition and Food Research. https://doi.org/10.1002/mnfr.202000936
  • Type: Journal Articles Status: Published Year Published: 2021 Citation: Bravo Iniguez, A., and M. J. Zhu. 2020. Hop bioactive compounds in prevention of nutrition-related noncommunicable diseases. Critical Reviews in Food Science and Nutrition, https://doi.org/10.1080/10408398.2020.1767537
  • Type: Journal Articles Status: Published Year Published: 2020 Citation: Tian, Q., Z. Xu, X. Sun, J. Deavila, M. Du, and M. J. Zhu. 2020. Grape pomace inhibits colon carcinogenesis by suppressing cell proliferation and inducing epigenetic modifications. Journal of Nutritional Biochemistry, 84:108443.
  • Type: Conference Papers and Presentations Status: Submitted Year Published: 2021 Citation: Bibi, S., Y. Xue, Y. He, M. Du, B. Chew, D. A. Navarre, and M. J. Zhu. 2021. Dietary purple potato supplementation ameliorates gut inflammation and associated colitis. American Nutrition Society Annual Meeting, Virtual, June 7-10, 2021.
  • Type: Conference Papers and Presentations Status: Submitted Year Published: 2021 Citation: Sun, Q., D. A. Navarre, M. Du, and M. J. Zhu. 2021. Cooking methods on extractability and bioactivity of polyphenolic compounds in purple potatoes. American Nutrition Society Annual Meeting, Virtual, June 7-10, 2021.
  • Type: Conference Papers and Presentations Status: Submitted Year Published: 2021 Citation: Wang, H., Q. Tian, Z. Xu, A. B. Iniguez, M. Du, and M. J. Zhu. 2021. Metabolomic profiling for the preventive effects of dietary grape pomace against colorectal cancer. American Nutrition Society Annual Meeting, Virtual, June 7-10, 2021.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2020 Citation: Tian, Q., Z. Xu, X. Sun, J. Deavila, M. Du, and M. J. Zhu. 2020. Grape pomace inhibits colon carcinogenesis by suppressing cell proliferation and inducing epigenetic modifications in an AOM/DSS mouse model. American Nutrition Society Annual Meeting, Seattle, Washington, June 1-4, 2020.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2020 Citation: Tian, Q., M. Du, Z. Xu, and M. J. Zhu. 2020. Sulforaphane protects against DSS-induced acute colitis. American Nutrition Society Annual Meeting, Seattle, Washington, June 1-4, 2020.


Progress 03/01/19 to 02/29/20

Outputs
Target Audience:Scientific community and commodity groups Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Two PhD students had been receiving training through this project. This project also provides training opportunities for a postdoc research associate and one undergraduate student. How have the results been disseminated to communities of interest?Peer-reviewed publications, meeting abstracts and presentations. What do you plan to do during the next reporting period to accomplish the goals?We will be continuing our research efforts on studying the beneficial effects of purple potatoes on gut health and exploring underlying mechanisms.

Impacts
What was accomplished under these goals? Perturbation of gut epithelial barrier function is a central pathogenic factor for gut inflammation and associated disorders, which are becoming common due to intake of western high fat diet and the prevalence of obesity. Purple potatoes contain a high level of beneficial polyphenolic compounds, which are hypothesized to have anti-obesity effects through improving gut barrier function, suppressing inflammation and preventing dysbiosis. We previously reported that polyphenol-rich purple potato extract enhances intestinal epithelial differentiation and improves gut barrier function, which reduces gut inflammation associated with high fat diet and further explored the regulatory roles of AMP-activated protein kinase. During the last period, we further studied the beneficial effects of dietary purple potatoes on gut health in vivo. Our studies showed that dietary purple potatoes ameliorated the inflammation and symptom of colitis in interleukin-10-deficient mice associated with improved gut structure and goblet cells. The analyses of gut samples and gut microbiota are ongoing. Additionally, we studied the protective effects of quercetin, a closely related polyphenol widely found in vegetables and fruits, against colonization of pathogenic bacteria in gut epithelium, a major cause of gut inflammation and associated diseases, which showed that polyphenol is beneficial against pathogenic bacteria in the gut inhabitation via interfering integrin β1 and focal adhesion kinase association.

Publications

  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Bibi, S., D. A. Navarre, X. Sun, M. Du, D. B. Rasco, and M. J. Zhu. 2019. Effect of potato consumption on gut microbiome and intestinal epithelial health. American Journal of Potato Research, 2019: 1-7.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: L.F. de Sousa Moraes, X. Sun, M. C. G. Peluzio, and M. J. Zhu. 2019. Anthocyanins /anthocyanidins and colorectal cancer: what is behind the scenes? Critical Reviews in Food Science and Nutrition, 59: 59-71
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Wang, H., S. Zhang, Q. Shen, and M. J. Zhu. 2019. A metabolome explanation on beneficial effects of dietary Goji on intestine inflammation. Journal of Functional Food, 53: 109-114.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Zhu, M. J., X. Sun, and M. Du. 2019. AMPK ablation aggravates colorectal tumorigenesis via epigenetic suppression of antioncogenes. Experimental Biology Meeting, Orlando, Florida, April 6-9, 2019.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Wang, H., S. Zhang, and M. J. Zhu. 2019. Fecal metabolomic response of IL-10-deficient mice supplemented with Goji. Experimental Biology Meeting, Orlando, Florida, April 6-9, 2019.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Xue, Y., M. Du, and M. J. Zhu*. 2019. Raspberry extract prevents Escherichia coli O157:H7-induced NLRP3 inflammasome activation. Journal of Functional Food, 56: 224-231.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Xue, Y., M. Du, and M. J. Zhu. 2019. Escherichia coli O157:H7 attaches to epithelial cells by stabilizing focal adhesions, a process suppressed by quercetin. Frontier Microbiology, 9: 3278.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Zhang, S, Wang, H., and M. J. Zhu. 2019. A sensitive GC/MS detection method for analyzing microbial metabolites short chain fatty acids in fecal and serum samples. Talanta,196: 249-254.


Progress 03/01/18 to 02/28/19

Outputs
Target Audience:Scientific community and commodity groups Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Two PhD students had been receiving training through this project. This project also provides training opportunities for a postdoc research associate and one undergraduate student. How have the results been disseminated to communities of interest?Peer-reviewed publications, meeting abstracts and presentations. What do you plan to do during the next reporting period to accomplish the goals?We will be continuing our research efforts on studying the beneficial effects of purple potato on gut health and exploring underlying mechanisms.

Impacts
What was accomplished under these goals? Proper intestinal barrier is essential for health, which is maintained by a delicate balance of epithelial proliferation and differentiation. Perturbation of gut epithelial barrier function induces inflammation and other health problems that originated from the gut. Purple potato contains a high level of beneficial polyphenolic compounds. During the past year, we have been conducting studies on the beneficial effects of polyphenol extracted from purple potato on intestinal barrier function and explore its underlying mechanism. We found that purple potato extract (PPE) increased transepithelial electrical resistance and decreased FITC-dextran paracellular flux in epithelial cells, which were associated with strengthened intestinal epithelial differentiation in intestinal epithelial cells and ex vivo cultured gut. Furthermore, PPE treatment enhanced AMP-activated protein kinase (AMPK) activity, concomitant with the increased expression of CDX2, a key transcriptional factor regulating intestinal epithelial differentiation. Knocking out AMPK using CRISPR/Cas9 system abolished the positive effects of PPE on intestinal epithelial differentiation and barrier function, in junction with the reduced expression of CDX2. Data collectively indicated that PPE improved gut epithelial differentiation and barrier function via activating AMPK. Butyrate, a gut microbial metabolite, is known for its beneficial effects for intestinal epithelial health. We found that butyrate suppresses proliferation, potentiates differentiation and induces apoptosis in human colonic epithelial cells via enhancing α-ketoglutarate-dependent DNA demethylation of mismatch repair genes. Data points to a close link among dietary polyphenols, gut microbial metabolites, and epigenetic modifications associated with intestinal health.

Publications

  • Type: Conference Papers and Presentations Status: Published Year Published: 2018 Citation: Zhu, M. J., and M. Du. 2018. Purple potato polyphenols target AMPK to improve gut epithelial health. 2018 Innovations in Food Science and Human Nutrition. Rome, Italy, September 13-15th, 2018.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2018 Citation: Zhu, M. J. 2018. Polyphenols and associated AMPK activation in management of inflammatory bowel disease. 2018 World Gastroenterology & Hepatology Conference, Rome, Italy, September 10-12th, 2018.
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Sun, X., M. Du, D. A. Navarre and M. J. Zhu. 2018. Purple potato extract promotes intestinal epithelial differentiation and barrier function by activating AMP-activated protein kinase. Molecular Nutrition and Food Research, 62:1700536.
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Sun, X., X. Fu, M. Du, and M. J. Zhu. 2018. Ex vivo gut culture for tracing gut epithelial development. Open Biology, 8: 170256.
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Sun, X., and M. J. Zhu. 2018. Butyrate inhibits indices of colorectal carcinogenesis via enhancing ?-ketoglutarate-dependent DNA demethylation of mismatch repair genes. Molecular Nutrition Food Research, 62: 1700932.
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Kang, Y., Y. Guan, S. Zhang, C. Ross, M. J. Zhu. 2018. Goji berry modulates gut microbiota and alleviates colitis in IL-10-deficient mice. Molecular Nutrition Food Research, 62: 1800535
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Zhu, M. J., X. Sun, X. Fu, and M. Du. 2018. AMPK in regulation of apical junctions and barrier function of intestinal epithelium. Tissue Barriers, 6: 1-13.
  • Type: Book Chapters Status: Published Year Published: 2018 Citation: Zhu, M. J. 2018. Dietary polyphenols, gut microbiota and intestinal epithelial health. In Nutritional and Therapeutic Interventions for Diabetes and Metabolic Syndromes. Page 295-314. Edited by Debasis Bagchi and Sreejayan Nair. 2nd eds. CRC press, Talyor & Francis.