Conferencia Inaugural

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1 Conferencia Inaugural UNDERSTANDING GASTRIC DIGESTION TO DEVELOP NEW FOODS FOR HEALTH R. Paul Singh Distinguished Professor of Food Engineering Department of Biological and Agricultural Engineering University of California, Davis, CA Dr. R. Paul Singh is a Distinguished Professor of Food Engineering, Department of Biological and Agricultural Engineering and Department of Food Science and Technology, University of California at Davis. He received his degrees in the area of agricultural engineering, with a Ph.D. from Michigan State University in His research involves transport phenomena in food processing and mathematical modeling to seek improvements in process efficiency. Dr. Singh is a Fellow of the Institute of Food Technologists. He is an author or co-author of 3 U.S. patents, 15 books, and over 260 refereed papers. He is currently serving as Editor-in-Chief of the Journal of Food Engineering. In 2008, Dr. Singh was elected to the U.S. National Academy of Engineering. In 2010, the Institute of Food Technologists awarded him the Nicolas Appert Award the highest award given in the field of food science in the United States. The focus of our current research is on understanding the breakdown of a food in the human stomach. From an engineering perspective, the human stomach is a receptacle, a grinder, a mixer and a pump that controls the digestion process. One of its major functions is to reduce the size of solid particulates and fat globules. The digestion process has been well studied in terms of secretion of gastric fluids, enzymatic breakdown of fats, proteins and carbohydrates, and molecular and ionic transport across the intestinal epithelium. However, there remains a notable lack of understanding about the food disintegration kinetics and the extraction of small molecules from complex food structures in the gastric environment. Furthermore, how the changes in food texture and microstructure (that define the material properties) resulting from various food processing affect gastric disintegration of foods is lacking. Our studies have involved in vitro, in vivo and in silico approaches. We have built a human gastric simulator to study food disintegration in a reactor that mimics human stomach. In vivo studies have been carried out using pigs that were fed selected diets of foods with different material properties. Computational models have been developed for a threedimensional domain representing a human stomach. These approaches are providing new insights about food digestion and release of nutrients. This information is useful in developing next generation of foods for health. VII Congreso Español de Ingeniería de Alimentos (CESIA 2012), Ciudad Real. [51]

2 Understanding Gastric Digestion to develop new Foods for Health R. Paul Singh Distinguished Professor of Food Engineering Department of Biological and Agricultural Engineering University of California, Davis, CA USA Nature creates foods with a diverse range of structures. Nutrients with potential health benefits are often embedded in the structural constructs of a food. While many foods are consumed in their raw form, others are processed to improve their shelf life or create new products. Modern food processing has evolved to carry out steps for the controlled destruction of natural food structures. These steps facilitate separation of valuable ingredients from the original matrix. The separated ingredients are then converted into recognizable processed foods with desirable textural and sensorial properties by application of one or more processing steps (Aguilera and Stanley, 1999). Until recently, the focus of research by most food scientists has remained on the farm-to-fork segment of the food chain. Published literature is replete with examples of scientific advances that have helped the food processing industry to develop novel products and processes to provide consumers with foods for improved health benefits. Recent evidence indicates that the way the food structure breaks down during gastric digestion will significantly affect the rate of nutrient uptake in the gastrointestinal (GI) tract. Therefore the knowledge and any capability to predict how a food may disintegrate in the stomach are important for developing future food products with novel health benefits. The understanding of the post-ingestion food behavior, specifically its quantitative aspects, can guide food processors to select appropriate ingredients and processing conditions at the time of manufacture. The focus of our current research is on understanding this admittedly complex subject, namely, the breakdown of a food in the human stomach. Looking through an engineer s lens, the human stomach may be considered as a small reservoir that functions as a grinder, a mixer and a pump that controls the digestion process. One of its major functions is to reduce the size of the solid particulates and fat globules. The stomach walls themselves do not absorb any nutrients except alcohol. The digestion process has been well studied in terms of secretion of gastric fluids, enzymatic breakdown of fats, proteins and carbohydrates, and molecular and ionic transport across the intestinal epithelium. However, there remains a notable lack of understanding about the food disintegration kinetics and the extraction of small molecules from complex food structures in the gastric environment. Furthermore, quantitative description of changes in the food texture and microstructure (that define the material properties) during gastric disintegration of foods is lacking.

3 Our key research objectives in pursuing gastric digestion of food are as follows. 1) Investigate the kinetics of food disintegration in human stomach as related to the raw and processed food material properties 2) Develop a computational model to predict the flow field and disintegration kinetic of foods with known physical properties during gastric digestion. 3) Conduct in vitro and in vivo trials with animal models to develop realistic understanding of gastric digestion of selected foods of known material properties. Approach: Our experimental approach to study gastric digestion of foods has involved the following steps: An in vitro stomach system was developed to mimic food disintegration process as observed from advanced imaging of human stomach. The disintegration rates of selected foods at different hydrodynamic and mechanical forces were determined. Mechanisms of the disintegration kinetic of foods were explored as related to the food structural/material properties. Texture of foods was assessed using a texture analyzer. Changes in the microstructure of foods during digestion were evaluated using imaging approaches such as scanning electron microscopy and magnetic resonance imaging. Statistical analysis was conducted to explore correlations between food texture, microstructure and disintegration kinetic. Empirical equations were developed to describe the disintegration kinetics with different influencing factors, such as the physico-chemical forces acting on the foods, exposure time, and food texture. The influence of food digestion on the rheological properties of gastric contents (chyme) was evaluated using a rheometer. Changes in the rheological properties of the digesta were determined. A 3-dimensional computational model of human stomach was developed using CFD solver (ANSYS_Fluent), quantifying the flow field within stomach and characterizing the changes of velocity and shear stress due to the peristaltic wall motion in a human stomach. The information on disintegration kinetics of foods and rheological properties of chyme from the experimental studies were combined to develop a model to predict the rate of food disintegration within the changing flow field in the stomach. In vivo trials using pig as an animal model were conducted to develop an understanding of gastric digestion. Specific trials included feeding pigs with foods of different material properties to determine the role of a stomach as a mixer and a grinder. Development of in vitro stomach models for food digestion research To study gastric digestion of foods, we developed two stomach models, a model stomach system (MSS) and a Human Gastric Simulator (HGS). These two models have different functions in food digestion studies. MSS is capable of providing stable mechanical force and flow condition for studying the dissolution and disintegration of individual food particulates,

4 providing information on the kinetics of disintegration as well as the effect of physiological conditions such as ph, enzymes, temperature, and mechanical forces (Fig. 1) (Kong and Singh 2008). This model was used to study the disintegration rate of different food matrices, as related to their structural and textural properties. HGS, containing a flexible-wall reactor, mimics the peristaltic movements of stomach walls (Fig. 2), and combines gastric secretion system for acids and enzymes, and a stomach emptying system (Kong and Singh 2010). Experiments show that the conditions such as mechanical forces and ph profiles simulated in the HGS are reliably reproduced and they are consistent with published data from in vivo trials (Kong and Singh 2010). HGS was used to simulate the disintengration of a food bolus in the stomach lumen, investigating the change in the ph, rheological properties of digesta, and the change in the microstructure of the food matrix. Figure 1. Model stomach system (MSS) Figure 2. Human gastric simulator (HGS) Digestion and disintegration kinetics of a food matrix in an in vitro stomach system Breakdown of solid foods during digestion is an important function of the stomach. We have studied how foods breakdown in a simulated human stomach under different conditions as related to the structure and textural properties of the food (Kong and Singh 2009a; 2009b; 2010; 2011). We have found two main disintegration modes of solid foods during gastric digestion: fragmentation and erosion. The disintegration rate is a combined effect of the stomach force, food texture and the changes in the texture during digestion. Different disintegration profiles were observed as a result of competition among surface erosion, water absorption and texture softening (Fig. 3). Foods with different initial structure upon disintegration may significantly affect the properties of the digesta. We have used particle size analyzer and rheometer to study how food

5 digestion may change the size distribution of food particles, and how this will affect rheological properties of the digesta. Food particulate during digestion c a b Tenderization front Soft layer Erosion front Tenderization front Soft layer Absorbed water W Wt/W0 t/w0 Wt/W a Disintegration time (min) b Disintegration time (min) c Disintegration time (min) Figure 3. A diagram showing that food gastric disintegration kinetics are affected by the competition among surface erosion, water absorption and texture softening, which cause three different disintegration profiles (weight retention ratio W t /W 0 ~ disintegration time), a: exponential, b: sigmoidal and C: delayed sigmoidal Diffusion of gastric and intestinal juice into food matrix plays a critical role in food digestion and disintegration. We have used magnetic resonance imaging (MRI) to investigate the diffusion of gastric juice into cooked rice, almond, and peanut kernels during gastric digestion. The data show that MRI is a promising tool for studying the diffusion of gastric and intestinal fluids into food matrix. MRI imaging showed a faster diffusion in cooked white rice than cooked brown rice, causing a faster degradation of texture and a faster disintegration and subsequently a faster stomach emptying time, validating our results obtained from the HGS. In vivo trials to study food digestion We have conducted in vivo trials using pigs to study the digestion of cooked white and brown rice to validate the in vitro data obtained in HGS. This study was conducted in collaboration with Massey University, New Zealand. The results validate in vitro results that cooked white rice has a faster stomach emptying than cooked brown rice. A more gel-like digesta was produced in stomach, and the change in ph of gastric content is slower than white rice (Fig. 4). These results show that food structure influences ph and viscosity of the digesta

6 and stomach emptying rate, which could significantly affect the efficacy of delivery systems contained in the food matrix. Figure 4. Comparison between white and brown rice after digestion in a pig stomach for 2 hours. Note the liquid-like semisolid digesta for white rice (left) and more solid-like digesta for brown rice (right). The rheological properties difference caused a much faster emptying in white rice and brown rice. (Note: blue dye was added to rice during cooking to observe the separation of bran layer during digestion) Computational flow modeling of the flow field in the human GI tract We have developed a 3-D computational model of human stomach to simulate the unsteady flow field generated inside human stomach due to the movement of contraction waves (Ferrua and Singh, 2010). The model used the Navier-stokes equations for fluid flow with deforming boundary walls. ANSYS(Fluent), a CFD solver, was used to solve the flow equations. The model demonstrated that as the antral contraction wave (ACW) moves towards the pyloric valve, a retrograde jet flow and eddy structures are created (Figure 5). Maximum fluid velocity was observed near the occlusion area of the ACW, closest to pylorus, and the strain rate was higher at those locations We also used a Particle Image Velocimetry (PIV) system to measure the flow behavior of fluid in a custom-built apparatus simulating peristaltic movement of the GI tract. The experimental results validate the computational predictions (Figure 6). This approach was used for numerical simulation of the flow and shearing force in both stomach and intestines.

7 Figure 5. Streamlines of the fluid flow within the stomach mid-plane at t + 10 s (maximum occlusion of gastric lumen 70%), colored by velocity (cm/s). a) Newtonian 1x10-3 Pa.s. Figure 6. Streamlines of Newtonian gastric flow (1 cp) at t+10 s, colored by velocity (cm/s). a) Within a 2-D representation of the stomach (non-slip condition). b) Within the middle plane of a 3-D model (free slip condition). Significance: Our ongoing research is aimed at enhancing our fundamental understanding of the disintegration of foods with different structural and material properties (i.e. microstructure and texture) during human gastrointestinal digestion. This knowledge is essential to assess the bioavailability of nutrients in the gastro-intestinal tract, and to develop innovative processing

8 conditions at the food manufacturing stage to develop structured foods for optimum and/or controlled release of nutrients in targeted regions of the gastro-intestinal tract. This knowledge, currently unknown, will be most helpful to food processors in developing next generation of foods for health. The study is also focused on developing new information for medical and nutritional researchers, particularly with regard to the role of food microstructures for control of stomach emptying to improve different clinical conditions such as obesity and diabetes. In addition, the kinetic information of food disintegration in stomach could contribute to the understanding of drug dissolution mechanisms in stomach and the interactions between food and drug during digestion thus benefit the pharmaceutical industry in optimizing drug dissolution behavior in the gastro-intestinal tract. References: Aguilera J M, Stanley D W Microstructural principles of food processing and engineering. Aspen Publishers Inc., Maryland, USA. Ferrua M and Singh R Modeling the Fluid Dynamics in a Human Stomach to Gain Insight of Food Digestion. Journal of Food Science. 75(7): R151 R162. Kong F and Singh R Solid loss of carrots during simulated gastric digestion. Food Biophysics. 6(1): Kong F and Singh R A human gastric simulator (HGS) to study food digestion in human stomach. Journal of Food Science 75(9): E Kong F and Singh R. 2009a. Modes of disintegration of solid foods in simulated gastric environment. Food Biophysics 4(3): Kong F and Singh R. 2009b. Digestion of raw and roasted almonds in simulated gastric environment. Food Biophysics 4(4): Kong F and Singh R A model stomach system to investigate disintegration kinetics of solid foods during gastric digestion. Journal of Food Science 73(5): E202 E210.

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