Progress 10/01/07 to 09/30/12
Outputs
OUTPUTS: Phenolic phytochemicals are secondary metabolites with diverse functional roles, in particular for managing biotic and abiotic stress responses in plants. Stress associated bioactive phenolic compounds from food-grade dietary plants specifically can be harnessed for human health applications. Among diverse phenolic moieties monophenolics, biphenolics and their polymeric derivatives have potential as antimicrobials. The major goal of this project was to harness the phenolic bioactive potential of soy phenolics from the biochemically active sprouting stage and from various stages of bioprocessing using yeast and lactic acid bacteria to inhibit ulcer associated Helicobacter pylori. This specific human pathogen causes chronic cases of ulcer and long term gastric disease leading to stomach cancer and being a microaerobic bacteria difficult to control using traditional antibiotic therapy. Bioactive food phenolics have the potential to inhibit specific steps in the microaerobic metabolic stages of H. pylori such as proline oxidation linked respiration. In addition the polymeric phenolics can disrupt membrane related functions. During the course of this study we have achieved the goal of generating soy phenolis from bioprocessed and fermentation stages to specifically inhibit H. pylori. Extending from this study we have also screened other legumes for H. pylori inhibitory activity. Since our studies indicated two types of potential inhibitory mechanism; one related to monophenolics inhibiting the microaerobic pathway and another biphenolic and polymeric phenolics disrupting potentially membrane associated functions, we extended our screening to other fruits (cherry) and medicinal teas that can compliment Soy-based foods and beverages as source of bioactive phenolics. Additionally these phenolics potentially being inhibitors of extracellular enzymes we extended our studies to explore and confirm that similar phenolic profiles also have dual function in inhibiting carbohydrate digesting (alpha-amylase) and uptake (alpha-glucosidase) pathways with implications for managing early stages of hyperglycemia associated with type 2 diabetes. PARTICIPANTS: The project directly supported 5 graduate students with stipends over the 6 years and indirectly supported 2 additional graduate students. Through these efforts graduate student training was enhanced. The project also provided professional development opportunity for 2 post-doctoral associates to direct and have supervisory experience with graduate students and also to explore ideas beyond the specific outlined goals of the project but closely related. We also collaborated with several companies that provided us cultures to explore bioactive enrichment. We plan to continue developing these concepts further. TARGET AUDIENCES: This project has targeted 4 major groups as a integrated foundation for developing plant-based therapeutic foods for managing chronic diseases: 1) Plant breeders and Agronomists to incorporate new health related bioactive strategies to develop new crops and especially cereals, legumes and fruits. 2) Food processing and food ingredient companies to incorporate bioactive food phenolic profiles into their food designs or use foods enriched in bioactive phenolics to improve health and wellness. 3) Starter culture companies to explore new strategies to develop food grade microbes for bioprocessing of foods for health. 4) Health care sector to explore therapeutic and functional foods as a part of their health delivery model, especially for chronic care management where drug therapies alone are failing. PROJECT MODIFICATIONS: Our initial focus of the proposed study was screening bioactive phenolics for H.pylori control and primarliy focused on soy and its bioprocessed sprout and fermented stages. As we gained initial clues that there could be different mechanism of action for monophenolics vs biphenolics and polymeric phenolics we extended our study to explore other legumes, fruits and medicinal teas to improve the range of beneficial food or beverage design for H.pylori control. Further we rationalized that the same phenolics may have dual function inhibitory activity that could be targeted to other disease pathways such as type 2 diabetes. Therefore we extended our study beyond soybean and also using the dual function of food crop phenolics to explore another disease pathway. This extension from the original goals has paid off in terms of better defining a foundation for developing crops and food processing systems for health. This foundation allows a more rationalized approach to develop crops, their processing stages and final food product to be better formulated and designed to affect health and wellness outcomes.
Impacts
There several major impacts from this project. First major impact is that we determined that several legumes, including soy have antimicrobial potential against ulcer bacteria H. pylori. This provides a rationale and foundation to develop food-based hurdles against this pathogen in combination with traditional antibiotic therapies. Further we gained initial insights that there could be 2 major mechanisms to inhibit this pathogen, one to disrupt its microaerobic dependance and second to disrupt membrane functions. From these clues we have extended our screening to other fruits and medicinal teas that could be additional synergies or combinations with soy and legume systems as basis for H.pylori management. Third exciting extension of the study is that several of the food phenolic profiles investigated in this study could also inhibit extracelluar enzymes associated with soluble carbohydrate metabolism. This dual function bioactive potential helps to target soy, other legumes, fruits and teas as food-based therapeutic counters measures for managing early stages of type 2 diabetes. Finally this also provides us a foundation to screen common food systems and their processing stages for bioactive potential to manage a range of chronic disease at the same time. These systems will have to be understood in more biochemical detail in terms of the structure-function mode of action to precisely manage these chronic disease and the accomplishments of ths project provide the clear rationale and direction for the next stage of investigation. The most exciting accomplishment from this study is an innovative paradigm to add value to crop and food systems for management of chronic disease and provide a better foundation for health and wellness through improved food systems. This study has supported directly or indirectly 7 graduate students over 6 years and 11 peer reviewed manuscripts have resulted from these efforts. In this final report we have added the last 3 published manuscripts.
Publications
- 1) Ankolekar, C., Johnson, D. R., Pinto, M.D.R., Johnson, K.C., Labbe, R.G. and Shetty, K. (2011) Inhibitory Potential of Tea Polyphenolics and Influence of Extraction Time Against Helicobacter pylori and Lack of Inhibition of Beneficial Lactic Acid Bacteria. Journal of Medicinal Food, 14:1321-1329.
- 2) Ankolekar, C., Pinto, M.D.S., Greene, D. & Shetty, K. (2011) Phenolic Bioactive Modulation by Lactobacillus acidophilus Mediated Fermentation of Cherry Extracts for Anti-Diabetic Functionality, Helicobacter pylori inhibition and Probiotic Bifidobacterium longum Stimulation. Food Biotechnology, 25: 305-335.
- 3) Ranilla, L.G., Apostolidis, E. and Shetty. K. (2012). Antimicrobial Activity of an Amazon Medicinal Plant (Chancapiedra) (Phyllanthus niruri L.) against Helicobacter pylori and Lactic Acid Bacteria. Phytotherapy Research, 26: 791-799.
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Progress 10/01/10 to 09/30/11
Outputs
OUTPUTS: Bioactive phenolic compounds with antioxidant potential from soybean and other legumes have potential to manage infections of ulcer bacteria, Helicobacter pylori. Further these bioactive phenolics have potential for combating oxidation-linked chronic diseases such as type 2 diabetes and associated complications by managing the gut uptake of soluble carbohydrates. Our research has used beneficial lactic acid bacteria to mobilize phenolic bioactives from soymilk during the processed stages. All the lactic acid bacteria fermented product extracts had inhibitory potential, except for Lactobacillus bulgaricus fermented soymilk. Further, the addition of cranberry - chitosan oligosaccharide mixture to the fermented substrates did not inhibit the growth of certain beneficial lactic acid bacteria such as Lactobacillus plantarum, but further enhanced H. pylori inhibition. The observed H. pylori inhibition was correlated to the increased total phenolic content in the fermented extracts due to cranberry phenolics. These results confirm the potential of lactic acid bacterial fermented soymilk products to inhibit H. pylori. When combined with cranberry phenolics and prebiotic chitosan oligosaccharide, the same lactic acid bacterial fermented extracts can be used as a natural constituent of multiple-barrier system to inhibit ulcer - linked H. pylori. PARTICIPANTS: Graduate student Chandrakant Ankolekhar worked on this project. This project helped train one graduate student and this graduate student supported research of several undergraduates. TARGET AUDIENCES: The knowledge from this research is useful to food processing industries working on food beverages for health and food industry focusing on development of functional foods. This knowledge is very useful to nutrition specialists and consumers who are looking at choice of better bioactive enriched food beverages for health and wellness. PROJECT MODIFICATIONS: We have some project modification since the mechanism of screening phenolics bioactives for health can be extended by combining with other food bioactives from cranberry, tea and marine sources to develop multifunctional and multi-ingredient designs where bacterial resistance can potentially be overcome.
Impacts
The targeting of beneficial lactic acid bacteria based fermentation strategies to enhance phenolic bioactives for managing bacterial infections is innovative. Fermentation bioprocessing of soy-milk combined with other botanical and natural bioactive substrates can extend the range of phenolic bioactives for ulcer bacteria inhibition. In this strategy as phenolic bioactives are enhanced during the processing stages it does not inhibit the beneficial lactic acid bacteria. This approach can also be used to enrich other lactic acid bacteria with prohibit potential and extend the natural designs for controlling Helicobacter pylori. The combinations of phenolic bioactives and probiotics can extend the range of bacterial pathogen inhibitory potential and exploits the differences in energy generation mechanisms. In many lactic acid bacteria the lack of oxygen dependency for energy generation via substrate level phosphorylation makes them less susceptible to the phenolic bioactives. Such innovative approaches can be the foundation of new antimicrobial designs for bacterial pathogens that depend on oxygen for energy generation.
Publications
- Apostolidis, E., Kwon. Y-I., Shinde. R., Ghaedian. G. and Shetty, K. (2011). Inhibition of Helicobacter pylori by fermented milk and soymilk using select lactic acid bacteria and possible link to enrichment of lactic acid and phenolic content. Food Biotechnology, 25: 58 - 76.
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Progress 10/01/09 to 09/30/10
Outputs
OUTPUTS: Phenolic bioactive compounds from soybean and other legumes have health benefits by managing potential infections such as ulcer bacteria (Helicobacter pylori) and also countering oxidation-linked chronic diseases such as type 2 diabetes and associated complications. We have extended our study to not only screen phenolic bioactives from a range of legumes and their processed stages but also are investigating the precise mode of action to control bacterial pathogens by breakdown of oxidative phosphorylation steps. In case of chronic diseases these legume bioactives can counter oxidation-linked disease pathways and in particular glucose uptake. We have developed new soymilk-based fruit fermentations to extend the range of beneficial bioactives with health benefits with above ulcer bacterial and glucose uptake inhibition targets. This increases the phenolic aglycones and organic acid profiles that inhibit ulcer bacteria. Initial results indicate the inhibition is linked to urease and oxidative phosphorylation inhibition. This mode of action of modulating nutrient utilization by soy and legume phenolics also has provided the rationale for anti-diabetes phenolic profiles from the same legume profiles. This offers a new innovative strategy that can be used to screen phenolic bioactives for other major chronic and infectious diseases. We have also leveraged and extended our studies to integrating fruit bioactives and range of the legume phenolic bioactives to improve the range of bioactive profiles that can be helpful to combating oxidation-linked chronic infections and disease conditions. PARTICIPANTS: Graduate student Chandrakanth Ankolekhar worked on this project. This project helped train one graduate student and this graduate student supported research of several undergraduates. Using the concepts of this research we also worked closely with collaborators in Brazil and Chile. TARGET AUDIENCES: The knowledge is useful for farmers, agricultural scientists working foods for health and food industry focusing on development of functional foods. The knowledge is very useful to consumers who are looking at choice of better plant foods to manage their health and wellness. PROJECT MODIFICATIONS: We have some project modification since the mechanism of screening phenolics bioactives for health related to ulcer bacteria have multi-purpose applications for health benefits for other chronic disease conditions such as type 2 diabetes management.
Impacts
The innovative functional food and ingredient design strategies from this research not only help to generate a range of phenolic bioactives for managing bacterial infections through nutrient uptake inhibition but the same rationale can be extended to other chronic diseases. At one level we are using fermentation bioprocessing of soy-milk and mixed legume substrates that can be combined with fruit phenolics to extend the range of phenolic bioactives for health benefits. At another level we are recruiting these phenolic profiles from range of plant foods in designing functional ingredients for combating chronic diseases such as type 2 diabetes and hypertension by inhibiting specific enzyme steps. Therefore, both design mechanisms using bioprocessing and better strategies for mode of action in specific disease states helps to develop the structure-function rationale for design of whole food functional bioactives. This offers a rationale approach for consistency of design based on health targets and mode of action. Such integration of approaches is required to extend the functional benefits of food ingredients and whole food systems for advancing foods for better health. The integration of profiles of legumes and fruits offers new innovative strategies to bring together range of phenolic profiles in a single whole food form using post-harvest stages and microbial bioprocessing.
Publications
- Ranilla, L.G., Apostolidis, E., Genovese, M.I., Lajolo, F.M. and Shetty. K. (2009) Evaluation of indigenous grains from the Peruvian Andean region for anti-diabetes and anti-hypertension potential using in vitro methods. J. Medicinal Food, 12: 704-713.
- Adyanthaya, I., Kwon, Y-I., Apostolidis, E. and Shetty, K. (2010) Health benefits of apple phenolics from post-harvest stages for potential Type 2 diabetes management using in vitro models. J. Food Biochemistry, 34: 31-49.
- Ranilla, L.G., Kwon, Y-I., Genovese, M.I., Lajolo, F.M. and Shetty. K. (2010) Effect of thermal treatment on phenolic compounds and functionality linked to type 2 diabetes and hypertension management of Peruvian and Brazilian bean cultivars (Phaseolus vulgaris L.) using in vitro methods. J. Food Biochemistry, 34: 329-355.
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Progress 10/01/08 to 09/30/09
Outputs
OUTPUTS: Food-based phenolic phytochemicals from legumes such as soybean and a range of other legumes in the sprouted and fermented stage can inhibit ulcer causing bacteria Helicobacter pylori. These phenolics can also control the carbohydrate nutrients that may be available for this bacteria and the antioxidant function that can stimulate the host cellular response to better combat the bacteria. In order to extend the range of food-grade phenolic phytochemicals available to combat this bacteria through the diet we have evaluated many legume sprouts and found many have the potential to inhibit the bacteria. Further we have extended the range of phenolic phytochemicals by combining soymilk and apple fermentation to enhance the antimicrobial phenolics combined with organic acids. This extension of substrates for lactic acid and mixed acid fermentations provides potent anti-ulcer phenolic aglycones combinations with organic acids. These combination profiles of phenolics and organic acid combine to inhibit H.pylori at energetic level by inhibiting micro aerobic function and also ability to combat high oxygen and free radical derivatives by inhibiting catalase. This means while bacterial catalase can be inhibited host catalase may not be affected due to its eukaryotic nature and compartmentalization. This rationale and mode of action of soy-mixed fermentation profiles is being pursued further. PARTICIPANTS: This project supported a graduate student and an undergraduate student in the summer to explore various soymilk and mixed fermentations to release functional phenolic phytochemicals and organic acids. TARGET AUDIENCES: The target audience for this research are food companies exploring new approaches and ingredients for designing foods to combat diet-linked chronic diseases. A second audience is the general consumer who as this research develops can see the health benefits of natural phenolic phytochemicals from regular lactic acid and acetic acid fermentation. As the science and clinical evidence develops such foods and ingredients can be incorporated into the diet based on the right design. PROJECT MODIFICATIONS: The basic approach to soy bioprocessing to enhance phenolics has not changed. However we have extended the range of phenolics by combining additional food substrates.
Impacts
The exciting impact of our research is that we can combine through soymilk fermentation a range of common food substrates such as apple and pear to enhance the range of phenolic phytochemicals and organic acids that can inhibit ulcer bacteria. Further some of the phenolics and organic acids in the same profiles can slow down carbohydrate metabolism that will likely reduce the energy needs of the bacterial pathogen. Additionally, some of the phenolics are antioxidant in nature and therefore have the potential to stimulate the host cells to combat the pathogenic better due to its micro aerobic-based energy needs, while good lactic acid bacteria are not affected. These soymilk and combined substrate fermentation has potential to impact strategies for designing food-based approaches to inhibit Helicobacter pylori that affects 50% of the world population. A second exciting potential of this research is that some of phenolic phytochemicals and organic acids in the sprouted and fermented profiles can inhibit enzymes associated with hyperglycemia and hypertension linked to type 2 diabetes. Overall this paves way for food bioprocessed strategies to design functional food ingredient profiles in whole food form to combat specific stages of chronic diseases, be it ulcer or stages of type 2 diabetes and its complications.
Publications
- Randhir, R., Kwon, Y-I., Lin, Y-T. and Shetty, K. 2009. Effect of thermal processing on phenolic associated health-relevant functionality of selected legume sprouts and seedlings. J. Food Biochemistry, 33: 89-112
- Randhir, R., Kwon, Y-I. and Shetty, K. 2009. Improved health-relevant functionality in dark germinated Mucuna pruriens sprouts by elicitation with peptide and phytochemical elicitors. Bioresource Technology, 100: 4507-4514.
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Progress 10/01/07 to 09/30/08
Outputs
OUTPUTS: Dietary phenolics from legumes and cereals in combinations with fermented organic acids have potential for chemoprevention of ulcer causing bacteria, Helicobacter pylori. To enhance chemprevention we have developed combinations of phenolics and organic acids by natural fermentation and bioprocessing by enhancement of sprouting-linked protective phenolics from legumes such as soybean. Many of these phenolics and organic acid have been targeted for disruption of energy pathways of Helicobacter pylori, specifically targeting proline oxidation. During past year we have continued to develop natural soy fermented systems using novel lactic acid bacteria and developed combinations of phenolics and lactic acid to inhibit Helicobacter pylori by inhibition of proline dehydrogenase to reduce energy generation of this microaerophillic bacteria and also targeted the inhibition of catalase that this critical to combat toxicity from higher oxygen. Specifically we have found a natural strain of Lactobacillus bulgaricus found in commercial yogurt and a strain of probiotic lactic acid bacteria, Lactobacillus acidophilus that can enhance phenolic and lactic acid profiles in fermented soymilk for the above critical inhibitory targets of Helicobacter pylori. Additionally we have now initiated studies to explore how other legumes and cereal phenolics also have potential for inhibition of Helicobacter pylori and whether such phenolic profiles can also inhibit glucose absorption in the gut that could have relevance for management of other chronic disease such as hyperglycemia linked to type 2 diabetes. Such a strategy can be have double benefits of controlling Helicobacter pylori and also combating specific pathways associated with better management of soluble carbohydrates linked to obesity and type 2 diabetes. PARTICIPANTS: During this period a part-time Post-doc and graduate student helped with the research reported. TARGET AUDIENCES: The targeted audience are food companies and nutritional support systems of hospital and medical establishments, including retired homes that are looking for practical ways to improve food quality for better health. PROJECT MODIFICATIONS: The major directions of using fermented and bioprocessed soybean have not changed. In addition, using the rationale of benefits of soybean we are exploring similar functionality in other legumes and cereals.
Impacts
The impact of our research is that by natural fermentation of soybean products such as soymilk and stress elicitation linked sprouting of commonly consumed legumes and cereals we can enhance bioactive phenolics and organic acids in a food background to inhibit ulcer-linked Helicobacter pylori. This provides an exciting food-based strategy to safely compliment other pharmaceutical-based strategies to combat ulcer-linked Helicobacter pylori that affects 50% of the global population. A second exciting offshoot of this research is that same phenolic and organic acid profiles have relevance for inhibiting pathways linked to hyperglycemia that is linked to management of type 2 diabetes. Therefore naturally enriching soybean and legumes as well as cereal food systems with these critical natural bioactives using biological and biochemical approaches many disease pathways have the potential to be continuously managed from moving towards deleterious cellular breakdowns causing eventual disease states, whether ulcers linked to Helicobacter pylori or hyperglycemia linked to type diabetes.
Publications
- 1) Burguieres, E., McCue, P., Kwon, Y-I. and Shetty, K. 2008. Health-related functionality of phenolic enriched pea sprouts in relation to diabetes and hypertension management. J. Food Biochemistry, 32:3-14.
- 2) Randhir, R., Kwon, Y-I. and Shetty, K. 2008. Effect of thermal processing on phenolics, antioxidant activity and health-relevant functionality of select grain sprouts and seedlings. Innovative Food Science and Emerging Technologies, 9:355-364.
- 3) Apostolidis, E., Kwon, Y-I., Labbe, R.G. and Shetty, K. 2008. Microbiology Division Poster at the Institute of Food Technology Conference, New Orleans, LA . Antimicrobial potential of milk and soymilk enriched with cranberry phenolics and fermented by lactic acid bacteria.
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Progress 10/01/06 to 09/30/07
Outputs
Several plant-derived compounds such as cinnamic acid, coumarins, and capsaicin in combination with fermented organic acids have been targeted for chemoprevention of ulcer causing Helicobacter pylori. To improve chemoprevention, effective control H. pylori through inhibition of critical control points that breakdown cellular energy and antioxidant pathways are essential. Results indicate that L-lactic acid promotes cell death by inhibition of proline dehydrogenase (PDH) which affects critical energy generation. This further enhances reactive oxygen species (ROS) with inability of catalase to counter ROS and therefore becomes lethal. Based on this knowledge lactic acid enriched soy-based fermented product extracts were evaluated and had inhibitory potential. Further, the addition of cranberry - chitosan oligosaccharide mixture to the fermented substrates further enhanced H. pylori inhibition. The observed H. pylori inhibition was correlated to the increased total phenolic
content in the fermented extracts due to cranberry phenolics. These results confirm the potential of lactic acid bacterial fermented soymilk products to inhibit H. pylori.
Impacts
The findings showed that lactic acid and phenolic phytochemical enriched fermented soymilk products can lead to new hurdle technology for controlling H.pylori. This can lead to new functional food designs using natural acid fermentation concepts for infection management linked to ulcer-causing H.pylori. This can help shape directions for value-added fermented foods for soybean industry and small processing companies. The rationale can also be extended to fermented dairy foods for value addition. From a health point of view fermented soy and milk-based products with phytochemical enrichment can be more cost-effective and simpler way for complimenting other pharmacological strategies for H.pylori ulcer management. The resources provided by this project helped support graduate student stipends to conduct this exciting research.
Publications
- Kwon,Y-I.,Apostolidis,E.,and Shetty,K. 2007. L-Lactic acid-induced cell death in Helicobacter pylori involves inhibition of proline oxidation and catalase-linked antioxidant response. Institute of Food Technology (IFT):Biotechnology Divsion Poster , Chicago, IL.
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