Computer modeling of digestive processes in the alimentary tract and their physiological regulation mechanisms: closing the gap between digestion models and in vivo behavior.

Introduction: A model has been developed for in silico simulation of digestion and its physiological feedback mechanisms. Methods: The model is based on known physiology described in the literature and is able to describe the complexity of many simultaneous processes related to food digestion. Results: Despite the early stage of development of the model, it already encompasses a large number of processes that occur simultaneously, enabling the prediction of a large number of post-prandial physiological markers, which can be highly functional in combination with in vitro, organ-on-a-chip and digital twin models purposed to measure the physiological properties of organs and to predict the effect of adjusted food composition in normal and diseased states. Discussion: Input from and collaboration between science fileds is needed to further develop and refine the model and to connect with in vitro, in vivo, and ex vivo (organ-on-a-chip) models.

Physiologically Based Modeling of Food Digestion and Intestinal Microbiota: State of the Art and Future Challenges. An INFOGEST Review.

This review focuses on modeling methodologies of the gastrointestinal tract during digestion that have adopted a systems-view approach and, more particularly, on physiologically based compartmental models of food digestion and host-diet-microbiota interactions. This type of modeling appears very promising for integrating the complex stream of mechanisms that must be considered and retrieving a full picture of the digestion process from mouth to colon. We may expect these approaches to become more and more accurate in the future and to serve as a useful means of understanding the physicochemical processes occurring in the gastrointestinaltract, interpreting postprandial in vivo data, making relevant predictions, and designing healthier foods. This review intends to provide a scientific and historical background of this field of research, before discussing the future challenges and potential benefits of the establishment of such a model to study and predict food digestion and absorption in humans.

Effects of inhomogeneity on triglyceride digestion of emulsions using an in vitro digestion model (Tiny TIM).

The colloidal behaviour and extent of lipolysis of various emulsions stabilized by whey protein and Tween were studied using the TNO Intestinal Model (TIM) extended with a purposely designed gastric compartment. The in vitro results suggest that creaming of a fatty layer in the gastric region causes a delay in fat entering the small intestinal region, delays and reduces the free fatty acid content in the small intestinal lumen and delays fat absorption. It was shown that controlling the pH with pig gastric juice instead of simulated gastric juice delayed creaming of the emulsions significantly, which resulted in faster gastric lipolysis. However, because the digestive conditions are not adjusted by physiological regulation mechanisms such as the regulation of gastric emptying by the detection of nutrients in the small intestine, care must be taken to translate these results to the in vivo reality. It is expected that the differences between the systems will be tempered by the physiological feedback regulation mechanisms of digestion.

Formation of ß Polymorphs in Milk Fats with Large Differences in Triacylglycerol Profiles.

In this study, we characterized the polymorphism of milk fat (MF) with various TAG compositions during isothermal crystallization at 20 °C. TAG composition of MF from seven individual cows was determined using GC-FID and MALDI-TOF MS, and MF polymorphism was studied using X-ray diffraction. Results showed that TAG profile determines the polymorphic behavior of MF. Saturated TAG with carbon numbers 34-38 promoted the formation of α polymorphs, whereas unsaturated TAG with 52-54 promoted the formation of the ß polymorphs. Furthermore, MFs with unsaturated fatty acid profiles were increased in unsaturated TAG with 52-54 carbons. The presence of MF crystals in the ß polymorph has been controversial over the years as most authors mainly find MF crystals in the α and ß' form. In our work, we showed that the ß polymorph is formed in MF on the basis of its TAG composition.

Specific food structures supress appetite through reduced gastric emptying rate.

The aim of this study was to determine the extent to which gastric layering and retention of a meal could be used to reduce appetite using the same caloric load. Liquid (control) and semi-solid (active) meals were produced with the same protein, fat, carbohydrate, and mass. These were fed to 10 volunteers on separate days in a crossover study, and subjective appetite ratings, gastric contents, and plasma cholecystokinin (CCK) were assessed over a period of 3 h. The active meal showed food boluses in the stomach persisting for ~45 min, slower emptying rates, and lower plasma CCK levels over the first hour. After the first hour, both gastric emptying rates and plasma CCK levels were similar for both systems and slightly increased compared with the unfed situation. Despite the lower plasma CCK levels for the active meal over the first hour, this meal reduced appetite more than the control meal over the 3 h of the study. For a moderately increased plasma CCK level in the fed state, appetite was correlated with the volume of gastric contents rather than gastric emptying rates or plasma CCK. This suggests that enhanced gastric retention was the key factor in decreasing appetite and was probably mediated by a combination of intestinal nutrient sensing and increased viscosity in the stomach.

Development of the Digestive System-Experimental Challenges and Approaches of Infant Lipid Digestion.

At least during the first 6 months after birth, the nutrition of infants should ideally consist of human milk which provides 40-60 % of energy from lipids. Beyond energy, human milk also delivers lipids with a specific functionality, such as essential fatty acids (FA), phospholipids, and cholesterol. Healthy development, especially of the nervous and digestive systems, depends fundamentally on these. Epidemiological data suggest that human milk provides unique health benefits during early infancy that extend to long-lasting benefits. Preclinical findings show that qualitative changes in dietary lipids, i.e., lipid structure and FA composition, during early life may contribute to the reported long-term effects. Little is known in this respect about the development of digestive function and the digestion and absorption of lipids by the newborn. This review gives a detailed overview of the distinct functionalities that dietary lipids from human milk and infant formula provide and the profound differences in the physiology and biochemistry of lipid digestion between infants and adults. Fundamental mechanisms of infant lipid digestion can, however, almost exclusively be elucidated in vitro. Experimental approaches and their challenges are reviewed in depth.

Colloidal aspects of texture perception.

Recently, considerable attention has been given to the understanding of texture attributes that cannot directly be related to physical properties of food, such as creamy, crumbly and watery. The perception of these attributes is strongly related to the way the food is processed during food intake, mastication, swallowing of it and during the cleaning of the mouth after swallowing. Moreover, their perception is modulated by the interaction with other basic attributes, such as taste and aroma attributes (e.g. sourness and vanilla). To be able to link the composition and structure of food products to more complicated texture attributes, their initial physical/colloid chemical properties and the oral processing of these products must be well understood. Understanding of the processes in the mouth at colloidal length scales turned out to be essential to grasp the interplay between perception, oral physiology and food properties. In view of the huge differences in physical chemical properties between food products, it is practical to make a distinction between solid, semi-solid, and liquid food products. The latter ones are often liquid dispersions of emulsion droplets or particles in general. For liquid food products for instance flow behaviour and colloidal stability of dispersed particles play a main role in determining their textural properties. For most solid products stiffness and fracture behaviour in relation to water content are essential while for semi-solids a much larger range of mechanical properties will play a role. Examples of colloidal aspects of texture perception will be discussed for these three categories of products based on selected sensory attributes and/or relevant colloidal processes. For solid products some main factors determining crispness will be discussed. For crispiness of dry cellular solid products these are water content and the architecture of the product at mesoscopic length scales (20-1000 microm). In addition the distribution of water at mesoscopic length scales was found to be important. For semi-solid foods, sensory characteristics as spreadability, watery and crumbliness are primarily determined by food properties at mesoscopic length scales. Crumbliness is directly related to the formation of free running cracks that occur during eating of the product. Exudation of the continuous liquid phase of gels during compression gives rise to watery/juicy sensory attributes. For liquid food products, colloidal interactions of emulsion droplets, particles, proteins, and polysaccharides with saliva and oral surfaces were found to affect texture characteristics as creaminess, fattiness, roughness and astringency.

Fat retention at the tongue and the role of saliva: adhesion and spreading of 'protein-poor' versus 'protein-rich' emulsions.

Fat perception of food emulsions has been found to relate to in-mouth friction. Previously, we have shown that friction under mouth-like conditions strongly depends on the sensitivity of protein-stabilized emulsion droplets to coalescence. Here, we investigated whether this also implies that oral fat retention depends in a similar manner on the stability of the emulsion droplets against coalescence. We investigate the separate contributions of droplet adhesion and droplet spreading to fat retention at the tongue, as well as the role of saliva. We perform ex vivo (Confocal Raman Spectroscopy; Confocal Scanning Laser Microscopy) experiments using pig's tongue surfaces in combination with human in vivo experiments. These reveal that protein-poor (unstable) emulsions are retained more at the tongue than protein-rich (stable) emulsions. Furthermore, the layer formed by adhering protein-poor droplets is more stable against rinsing. Saliva is found to be very efficient in removing fat and emulsion droplets from the oral surface but its role in fat retention needs further research. We relate our results to the colloidal forces governing droplet adhesion and spreading.

Direct observation of adhesion and spreading of emulsion droplets at solid surfaces.

Sensory perception of fat is related to orally perceived in-mouth friction. From this perspective, we investigate adhesion and spreading of emulsion droplets on solid surfaces and connect it to the ability of food emulsions to lower friction. Furthermore, we study what the contribution is of the separate colloidal forces on droplet adhesion. The effect of saliva on adhesion and spreading is also briefly investigated. Using a flow cell in combination with light microscopy and video imaging allowed us to clearly distinguish between adhered and spread emulsion droplets. The capability to make this distinction between adhesion and spreading experimentally is new and provided us with the insight that the occurrence of spreading is essential for lowering friction. Mainly electrostatic, steric and hydrophobic interactions of the droplets with solid surfaces are found to determine adhesion and subsequent spreading of emulsion droplets. This was investigated by varying the adsorbed amount of protein, the ionic strength of the emulsion as well as the hydrophobicity of the solid surface. Especially the hydrophobic interaction between droplet and surface is shown to be crucial for droplet adhesion and spreading. Saliva is of minor importance for adhesion and spreading. This work gives insight in the way emulsion droplets interact with solid surfaces and the type of colloidal interactions that play a role. The information it provides can be used to develop emulsions that are reasonably stable during the shelf life of the product, but do spread on oral surfaces, thus lowering friction and enhancing fat perception.

Complex formation in mixtures of lysozyme-stabilized emulsions and human saliva.

In this paper, we studied the interaction between human unstimulated saliva and lysozyme-stabilized oil-in-water emulsions (10 wt/wt% oil phase, 10 mM NaCl, pH 6.7), to reveal the driving force for flocculation of these emulsions. Confocal scanning laser microscopy (CSLM) showed formation of complexes between salivary proteins and lysozyme adsorbed at the oil-water interface and lysozyme in solution as well. To assess the electrostatic nature of the interaction in emulsion/saliva mixtures, laser-diffraction and rheological measurements were conducted in function of the ionic strength by adding NaCl to the mixture in the range between 0 and 168 mM. Increasing the ionic strength reduced the ability of saliva to induce emulsion flocculation as shown by the decreased floc size and the effect on the viscosity. Turbidity experiments with varying pH (3-7) and ionic strength also showed decreased complex formation in mixtures between saliva and lysozyme in solution upon NaCl addition up to 200 mM. Decreasing the pH increased the turbidity, in line with the increase of the positive net charge on the lysozyme molecule. We conclude that electrostatic attraction is the main driving force for complex formation between saliva components and lysozyme adsorbed at the oil droplets and in solution.

Scaling behavior of delayed demixing, rheology, and microstructure of emulsions flocculated by depletion and bridging.

This paper describes an experimental comparison of microstructure, rheology, and demixing of bridging- and depletion-flocculated oil-in-water emulsions. Confocal scanning laser microscopy imaging showed that bridging-flocculated emulsions were heterogeneous over larger length scales than depletion-flocculated emulsions. As a consequence, G' as determined from diffusing wave spectroscopy (DWS) corresponded well with G' as measured macroscopically for the depletion-flocculated emulsions, but this correspondence was not found for the bridging-flocculated emulsions. The heterogeneity of bridging-flocculated emulsions was confirmed by DWS-echo measurements, indicating that their structure breaks up into large fragments upon oscillatory shear deformation larger than 1%. Depletion- and bridging-flocculated emulsions showed a different scaling of the storage modulus with the volume fraction of oil and a difference in percolation threshold volume fraction. These differences will be discussed on the basis of the two types of droplet-droplet interactions studied. Gravity-induced demixing occurred in both emulsions, but the demixing processes differed. After preparation of bridging-flocculated emulsions, serum immediately starts to separate, whereas depletion-flocculated systems at polysaccharide concentrations in the overlap regime usually showed a delay time before demixing. The delay time was found to scale with the network permeability, B; the viscosity, eta, of the aqueous phase; and the density difference between oil and water, Deltarho, as tdelay approximately B(-1)etaDeltarho(-1). The results are in line with the mechanism proposed by Starrs et al. (J. Phys.: Condens. Matter 2002, 14, 2485-2505), where erosion of the droplet network leads to widening of the channels within the droplet networks, facilitating drainage of liquid.