No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Dynamic gastric model (DGM): A novel in vitro apparatus to assess the impact of gastric digestion on the droplet size of self-emulsifying drug-delivery systems
... There is significant variation in what is considered to be the average biochemical composition of the adult digestive tract, although there are two notable efforts (INFOGEST and ORBIT consortia) to harmonize opinion on this [49,107] and a new consensus model has been proposed [49]. Several dynamic in vitro models of gastric digestion (e.g., "TIM 1" and "DGM") have been created to simulate the constant change in gastric pH upon meal consumption [108][109][110][111][112][113][114]. The TIM series of models (TIM 1 and recent tiny TIM) was created by Minekus et al. at TNO (Nederlandse Organisatie voor Toegepast Natuurwetenschappelijk Onderzoek) and are a highly relevant mimic of the dynamics of gastric secretions and peristalsis in a series of interconnected compartments [108][109][110]. ...
... The TIM series of models (TIM 1 and recent tiny TIM) was created by Minekus et al. at TNO (Nederlandse Organisatie voor Toegepast Natuurwetenschappelijk Onderzoek) and are a highly relevant mimic of the dynamics of gastric secretions and peristalsis in a series of interconnected compartments [108][109][110]. The DGM of the team at IFR and Nottingham uses knowledge from magnetic resonance imaging (MRI) studies to simulate antral grinding and gastric emptying in addition to dynamically mimicking gastric secretions (i.e., pH) [113,114]. ...
Lipids play an important role in the diet of preterm and term infants providing a key energy source and essential lipid components for development. Whilst a lot is known about adult lipid digestion, our understanding of infant digestion physiology is still incomplete, the greatest gap being on the biochemistry of the small intestine, particularly the activity and relative importance of the various lipases active in the intestine. Literature has been reviewed to identify the characteristics of lipid digestion of preterm and term infants, but also to better understand the physiology of the infant gastrointestinal tract compared to adults which impacts the absorption of lipids. The main differences are a higher gastric pH, sub micellar bile salt concentration, a far more important role of gastric lipases as well as differences at the level of the intestinal barrier. Importantly, the consequences of improper in vitro replication of gastric digestions conditions (pH and lipase specificity) are demonstrated using example from the most recent of studies. It is true that some animal models could be adapted to study infant lipid digestion physiology, however the ethical relevance of such models is questionable, hence the development of accurate in vitro models is a must. In vitro models that combine up to date knowledge of digestion biochemistry with intestinal cells in culture are the best choice to replicate digestion and absorption in infant population, this would allow the adaptation of infant formula for a better digestion and absorption of dietary lipids by preterm and term infants. This article is protected by copyright. All rights reserved.
... Therefore, to solve this problem, gastric digestion simulators (GDSs) that mimic peristalsis have been developed and used in digestion experiments using various food models. 11,12 Kozu et al. 13 developed a human GDS that enables real-time observation of physical digestion driven by peristalsis. ...
BACKGROUND
There is limited knowledge regarding digestion and absorption of nutrients after cooked marinated meat is ingested. Most of the previous studies on food gastric digestion have focused on chemical digestion and did not reflect upon physical digestion driven by peristalsis. In the present study, we examined the effects of marinating beef in lemon juice on gastric digestibility using a human gastric digestion simulator (GDS) that mimics peristaltic motion called antral contraction waves.
RESULTS
Beef thigh slices were marinated in 100% lemon juice for 1 h and then grilled; an image of a stained tissue sample revealed that muscle tissue contraction (i.e. that usually occurs upon cooking) was suppressed. The measurement of physical properties using a rheometer and texture analyzer showed that the meat marinated in lemon juice had a soft texture. In vitro digestion experiments using the GDS revealed that the extent of both physical digestion driven by peristalsis and chemical digestion catalyzed by digestive enzymes was enhanced by the lemon juice marinade.
CONCLUSION
The results of the present study suggest that marinating beef in lemon juice affects nutrient digestibility. An integrated evaluation of tissue structure, physical properties and GDS digestion to analyze meat digestion would enhance our understanding of the effects of seasoning and cooking methods on meat. © 2023 Society of Chemical Industry.
... To achieve this case-by-case simulation, numerous dynamic human digestion models have been created. Some of them concentrate on mimicking the chemical environments and physical behaviours present in the gastrointestinal tract, including the TNO's gastrointestinal model (TIM-1) (Minekus et al., 1995), the dynamic gastric model (DGM) (Mercuri et al., 2008), the human gastric simulator (HGS) (Kong & Singh, 2010), and the human gastric digestion simulator (GDS) (Kozu et al., 2014). Besides the simulation of these physicochemical conditions, several dynamic digestion models further imitate the anatomical and inner wrinkled structures of the human stomach, like the ropedriven in vitro human stomach (RD-IV-HSM) (Chen et al., 2016), and the near real dynamic in vitro human stomach (DIVHS) (Wang et al., 2019). ...
A dynamic in vitro human stomach (DIVHS), simulating the anatomical structures, peristalsis, and biochemical environments of a real stomach as practically as possible, was applied to mimic the gastric pH and emptying during yogurt digestion in short/long gastric residence times. The influences of peristalsis, dilution, and proteolysis on digesta viscosity were quantified respectively, indicating the dominant role of proteolysis and dilution. After incorporating curcumin-whey protein microparticles with targeted-release formula in yogurt, the peak curcumin release during intestinal digestion reached 43% at 120 min in the short gastric residence time and 16% at 180 min in the long gastric residence time. The change in the maximum curcumin release depended on the gastric emptying kinetics in each residence time. This emptying-kinetics dependence was reflected by the slower microparticle disintegration and proteolysis in the long gastric residence time. The dynamic reproduction of realistic gastric conditions using DIVHS helps revealing controlled release from foods.
... Page 46 sur 246 Digesteur dynamique mono-compartimental « DGM » (Mercuri et al., 2008 ;Whickam et al. 2012) Digesteur dynamique mono-compartimental « Human Gastric Simulator» ou « HGS » (Kong et al., 2010) Digesteur dynamique multi-compartimental encemencé « Simulators of the Human Intestinal Microbial Ecosystem » ou « SHIME » (Molly et al., 1993 ;Van den Abbeele et al., 2010) Digesteur dynamique bi-compartimental (Mainville et al., 2005) Digesteur dynamique mono-compartimental « Human Gastric Simulator» ou « HGS » (Kong et al., 2010) Page 47 sur 246 ...
Worldwide, the Food Industry uses a broad range of
microorganisms while making fermented products, like cheese,
most of microorganisms being alive when the food is consumed.
Our work aimed at studying the digestive stress response of the
surface-ripened cheese microflora and at characterizing their
potential immunomodulative properties.
In the first part of this work, we investigated the resistance to
digestive stress of a selection of 35 microorganisms (bacteria,
yeasts and one fungus). We designed a three-step in vitro
digestive batch experiment mimicking stresses encountered in
(i) the stomach, (ii) the duodenum, (iii) the stomach followed by
the duodenum. Alongside, we determined in vitro the
microorganisms immunomodulating properties using PBMCs.
Batch stress experiments results showed a strong resistance of
yeasts to both gastric and duodenal stresses. Bacteria results
were more contrasted. PBMCs profiles showed an overall antiinflammatory
response for yeasts (with the exception of one
species) while bacteria profiles were fairly different, with both
pro- and anti-inflammatory profiles among the same species.
The second part of the work consisted in developing a Dynamic
Gastro-Intestinal Digestive system (DIDGI) and to experiment on
a reduced selection of microorganisms and to assess the
influence of the growth under real ripening conditions on the
ability of microorganisms to withstand digestive stress.
Alongside, we tracked the microorganisms’ ability to survive the
mouse digestive tract. Some microorganisms grown in cheeses
showed fairly different responses during DIDGI experiments
compared to lab-cultured microorganisms. A significant part of
microorganisms was able to survive the digestive tract of mice.
The third part of the work dealt with the microbial ecosystems'
influence on the host's immune responses by (i) designing
experimental smear-ripened cheeses with mix of
microorganisms that had rather pro- or rather antiinflammatory
immunomodulatory profils and (ii) fed the ripened
cheeses to mice with standardized microbiota. The effect of
cheeses consumption on two different models of acute colitis
was investigated. Results showed that both cheeses tend to
exacerbate the symptoms in one of the colitis model and that the
“pro-inflammatory” cheese significantly aggravated the
symptoms of the second model of colitis.
The fourth and last part of the work consisted in characterizing
the molecular response to a similar in vitro batch digestive stress
used in the first part of the work. Therefore, we selected a Grampositive
bacterium and a Gram-negative bacterium and used
RNAseq for transcriptome analysis. A preliminary analysis of the
results showed that both organisms were able to up- or downregulate
a major part of their metabolism, using both similar
mechanisms and specific response per bacterium.
... The muscle tissue of these digestive tract organs can be peristaltic and contracted, and there is no mixing device like a stirring paddle inside to promote mixing in the lumen. After that, the researchers performed a series of in vitro simulations of the human stomach, which reproduced the digestive process of the stomach to some extent Kong and Singh, 2010;Kozu et al., 2014;Mercuri et al., 2008). In vitro rat systems was also constructed to study the effects of wall motion on the digestive process (Chen et al., 2013a(Chen et al., , 2013b. ...
Inspired by the mixing process in the digestive tract of the organism, a soft-elastic reactor (SER) was designed. This type of reactor demonstrated advantages in mixing highly-viscous fluids. The mixing mechanisms, however, remain unclear and the mixing performance is yet to be improved. This paper established a numerical simulation model for the mixing process in this special type of reactor with bionic contractions. The effects of different wall motion types and reactor sizes on the mixing process were systematically investigated through in silico experiments. The results show that a reactor featuring both peristalsis and segmentation movements offers decent mixing efficiency. A rational design of the SER should promote convective movement of fluids in the complete SER, taking care of not only the fluid velocity magnitude but also the flow directions.
... 8 However, they oversimplify the digestive physiology resulting in the failure to mimic the complex dynamic digestion process occurring in vivo in which digestive secretion, gastric digestion and emptying occur simultaneously. 1,4 Some more sophisticated and representative dynamic human digestion systems include the TNO's gastrointestinal model (TIM), 9 the human gastric simulator (HGS), 10 the dynamic gastric model (DGM) 11 and the human gastric digestion simulator (GDS). 12 Their structural features, advantages, limitations and main applications have been reviewed elsewhere. ...
A near real dynamic in vitro human stomach (new DIVHS) system has recently been advanced in this study, based on the previous rope-driven in vitro human stomach model (RD-IV-HSM). The new DIVHS mainly consists of the J-shaped silicone human stomach model fabricated with 3D-printing technology which has similar stomach morphology, dimension and wrinkled inner structure to that present in vivo, and the electromechanical instrument composed of a series of motors, rollers and eccentric wheels to produce peristaltic contractions. The simulated stomach system was able to generate consistent gastric emptying ratios of both the solid and liquid fractions in the beef stew mixed with orange juice with that reported in vivo (p>0.05). By fitting the gastric retention data with a modified power-exponential model, the solid fractions showed average emptying half-time (t1/2) of 74.1 min and lag phase (tlag) of 36.3 min in the new DIVHS, similar to that obtained in vivo where the average values of t1/2 and tlag were 75.8 min and 40.2 min, respectively. The performance of the new DIVHS was further validated by showing good qualitative matches of the gastric pH, particle size distribution and emptying profiles of cooked rice with the literature in vivo data. These results indicate that it is a reasonable approach to perform in vitro gastric digestion experiments using the new DIVHS, which is practically meaningful.
... However, these methods cannot reasonably consider the physical forces caused by human gastric peristalsis. Complex in vitro gastric (and gastrointestinal) digestion devices equipped with segmentation or peristalsis have been developed by research groups in Europe (Minekus et al. 1995, Mercuri et al. 2008. These devices realize the automated operation of in vitro gastric digestion experiments. ...
Gastric digestion is the major digestion process in humans and is strongly affected by both physical and chemical digestion. In vitro approaches using different gastric digestion models have received a great deal of attention in several scientific and industrial fields, including food science and technology, due to experiments being conducted under various conditions and with better reproducibility of the experiment data. The development of simple in vitro gastric digestion devices that enable quantitative consideration of the influence of gastric peristalsis has been necessary for simulating and analyzing the disintegration of solid foods in the stomach. The authors and co-workers recently developed a human gastric digestion simulator (GDS) that simplifies the antrum geometry, is capable of simulated gastric peristalsis, and which enables direct observation of the disintegration of food particles in the gastric contents. This article provides a brief overview of our findings regarding the GDS. First, the concept and development of the GDS is introduced. The disintegration characteristics of representative (model) foods using the GDS are described next, providing insights into the digestion processes influenced by gastric peristalsis. After further improvement, the GDS is expected to offer potential as a tool for designing novel nutraceutical and functional foods for which digestibility is well controlled.
... absorption and diffusion) and rheological aspects (i.e. mixing) (Blanquet et al., 2004;Dekkers, Kolodziejczyk, Acquistapace, Engmann, & Wooster, 2016;Kong & Singh, 2010a;Levi & Lesmes, 2014;Mercuri, Lo Curto, Wickham, Craig, & Barker, 2008;Shani-Levi, Levi-Tal, & Lesmes, 2013;Tharakan, Norton, Fryer, & Bakalis, 2010;Yoo & Chen, 2006). To date, both advanced and simple IVD models have be used to investigate a variety of systems. ...
Background. In vitro digestion models show great promise in facilitating the rationale design of foods. This paper provides a look into the current state of the art and outlines possible future paths for developments of digestion models recreating the diverse physiological conditions of specific groups of the human population.
Scope and Approach. Based on a collective effort of experts, this paper outlines considerations and parameters needed for development of new in vitro digestion models, e.g. gastric pH, enzymatic activities, gastric emptying rate and more. These and other parameters are detrimental to the adequate development of in vitro models that enable deeper insight into matters of food luminal breakdown as well as nutrient and nutraceutical bioaccessibility. Subsequently, we present an overview of some new and emerging in vitro digestion models mirroring the gastro-intestinal conditions of infants, the elderly and patients of cystic fibrosis or gastric bypass surgery.
Key Findings and Conclusions. This paper calls for synchronization, harmonization and validation of potential developments in in vitro digestion models that would greatly facilitate manufacturing of foods tailored or even personalized, to a certain extent, to various strata of the human population.
... On the other hand, dynamic models take into account temporal features of digestion, such as gut motility and fluid motion [46,47]. The importance of dynamic models has long been acknowledged [48], and a number of models have since been developed to mimic oral [49][50][51][52][53], gastric [54][55][56][57][58][59] or intestinal [46,60] digestion, or a combination of those [45,[61][62][63][64][65][66]. Such models have been used to evaluate the bioavailability of active components [67,68], stability of antioxidants such as xanthophylls [69] and micronutrients such as iron, folic acid and ferulic acid [70], the effect of allergens in foods [71], release of nutrients or bioactive components [58], performance of functional foods and survival of probiotics [56,72,73]. ...
Purpose:
The rate and extent of starch digestion have been linked with important health aspects, such as control of obesity and type-2 diabetes. In vitro techniques are often used to study digestion and simulated nutrient absorption; however, the effect of gut motility is often disregarded. The present work aims at studying fundamentals of starch digestion, e.g. the effect of viscosity on digestibility, taking into account both biochemical and engineering (gut motility) parameters.
Methods:
New small intestinal model (SIM) that realistically mimics gut motility (segmentation) was used to study digestibility and simulated oligosaccharide bio accessibility of (a) model starch solutions; (b) bread formulations. First, the model was compared with the rigorously mixed stirred tank reactor (STR). Then the effects of enzyme concentration/flow rate, starch concentration, and digesta viscosity (addition of guar gum) were evaluated.
Results:
Compared to the STR, the SIM showed presence of lag phase when no digestive processes could be detected. The effects of enzyme concentration and flow rate appeared to be marginal in the region of mass transfer limited reactions. Addition of guar gum reduced simulated glucose absorption by up to 45 % in model starch solutions and by 35 % in bread formulations, indicating the importance of chyme rheology on nutrient bioaccessibility.
Conclusions:
Overall, the work highlights the significance of gut motility in digestive processes and offers a powerful tool in nutritional studies that, additionally to biochemical, considers engineering aspects of digestion. The potential to modulate food digestibility and nutrient bioaccessibility by altering food formulation is indicated.
... Chemical environments including pH, salt, and digestive enzymes have been simulated using artificial digestive juices inside test vessels [3][4][5][6]. A more complex digestion system has also been proposed [7][8]. Physical digestion is especially important in the case of solid food, since the size reduction of solid food by breaking down must promote enzyme reactions. ...
This study investigates the ef fect of the texture of agar gel as a model solid food on gastric digestion using a human Gastric Digestion Simulator (GDS). The GDS, which simulates gastric peristalsis, can investigate physical digestion phenomena such as disintegration of solid foods. Agar gels with different fracture stresses (56 to 219 kPa) and constant fracture stain (29%) were prepared by var ying the agar concentration (1.5 to 4.5 wt%). Direct obser vation demonstrated that agar gel particles initially cut to a 5.0 mm cube gradually reduced in size and broke down into random shapes during simulated gastric peristalsis. The size distribution of the agar gel particles after the digestion experiment was analyzed using the sieving method. The fraction larger than 2.36 mm, which corresponds to the pylorus size, decreased with time: the wet weight ratio of that fraction to the total amount of agar gel particles was 18.0% at 180 min in the case of 1.5 wt% agar gel. The agar gel concentration did not affect the size distribution after 180 min, which shows that fracture strain plays a more important role in agar gel digestion. Our results provide useful information about the relationship between solid food texture and gastric digestion. © 2015, Japan Society for Food Engineering. All rights reserved.
... Compared to static models, dynamic ones present the advantage of simulating the complex evolution over time of the main physico-chemical and mechanical phenomena occurring during digestion, such as pH changes, realistic gastrointestinal transit time and variable mechanical forces (Guerra et al., 2012). As an example, the Dynamic Gastric Model -DGM- (Mercuri et al., 2008) and the Human Gastric Simulator -HGS- (Kong and Singh, 2010) are dynamic stomach models closely mimicking gastric anatomy and peristaltic movements. Multi-compartmental systems offer a simple access to the different parts of the digestive tract, giving instant information about the fate of compounds in the gastrointestinal environment. ...
For ethical, regulatory, and economic reasons, in vitro human digestion models are increasingly used as an alternative to in vivo assays. This study aims to present the new Engineered Stomach and small INtestine (ESIN) model and its validation for pharmaceutical applications. This dynamic computer‐controlled system reproduces, according to in vivo data, the complex physiology of the human stomach and small intestine, including pH, transit times, chyme mixing, digestive secretions, and passive absorption of digestion products. Its innovative design allows a progressive meal intake and the differential gastric emptying of solids and liquids. The pharmaceutical behavior of two model drugs (paracetamol immediate release form and theophylline sustained release tablet) was studied in ESIN during liquid digestion. The results were compared to those found with a classical compendial method (paddle apparatus) and in human volunteers. Paracetamol and theophylline tablets showed similar absorption profiles in ESIN and in healthy subjects. For theophylline, a level A in vitro–in vivo correlation could be established between the results obtained in ESIN and in humans. Interestingly, using a pharmaceutical basket, the swelling and erosion of the theophylline sustained release form was followed during transit throughout ESIN. ESIN emerges as a relevant tool for pharmaceutical studies but once further validated may find many other applications in nutritional, toxicological, and microbiological fields. Biotechnol. Bioeng. 2016;113: 1325–1335. © 2015 Wiley Periodicals, Inc.
... Examples of these systems are the TNO TIM-1 system (17) and the dynamic gastric model (DGM). The DGM, developed by the Institute of Food Research in Norwich, UK, is designed to simulate the human gastric compartment of the fundus and antrum (18,19). It is the first "dynamic" in vitro model that replicates both the complex biochemical conditions and the array of gastric hydrodynamics, critical for the prediction of digestive processes and the bioperformance of pharmaceutical agents and dosage forms. ...
Even in the 21st century, conventional compendial dissolution testing remains a key cornerstone of the drug development process and quality control testing. However, opportunities exist with respect to in vitro technology developments that provide the potential for formulation and analytical scientists to exceed the capabilities of the conventional dissolution test toward a more biorelevant testing regime. This work presents a product development case study in which bioequivalence was observed between an immediate-release (IR) innovator product and a comparative singlelayer reference product. Despite this, when the constituent granule of the comparative single-layer reference product was formulated in a bilayer formulation with a nondisintegrating second layer, bioequivalence versus the innovator was not achieved. The use of USP Apparatus 2 dissolution testing failed to predict the bioequivalence failure, and hence an investigation was undertaken to develop a mechanistic understanding of in vivo behavior. Using both USP Apparatus 4 dissolution in the open-loop configuration and the dynamic gastric model (a novel in vitro model designed to mimic the human stomach), an understanding of the dissolution and disintegration properties of the reference product was established. The insights gained using novel technology facilitated the redesign and subsequent improvement in pharmacokinetic parameters of a complex pharmaceutical dosage form.
... This device can be used to control the pH, temperature, and secretion of gastrointestinal fluids (Blanquet-Diot, Soufi, Rambeau, Rock, & Alric, 2009). Mercuri, Lo Curto, Wickham, Craig, and Barker (2008) designed a fully automated human gastric system that can simulate gastric secretion and emptying using a fixed outer cylinder with a movable inner cylinder to crush foods, eventually breaking them down by mechanical effect. These dynamic devices are very useful for analyzing chemical digestion but have difficulty detecting bulk solid foods due to the lack of the antral contraction wave that plays a major role in physical digestion. ...
This study evaluates physical digestion for cooked white rice and cooked brown rice using a novel in vitro gastric digestion simulator (GDS). The GDS enabled direct observation of the disintegration of cooked rice in the presence of simulated human gastric peristalsis. The experiments confirmed a steep increase in the disintegration of cooked white rice during the initial 30 min, after which disintegrated contents slowly increased. However, the appearance of liquid phase had little effect on cooked brown rice up to 180 min digestion, likely due to the protective action of the bran layer. Our results indicated that cooked rice particles gradually disintegrated into smaller fractions, depending on the type of cooked rice. The present research uses GDS to provide a better understanding of solid food digestion.
... pH electrodes directly immersed within the DGM content monitor the pH changes within the "meal" over time and control the rate and amount of acid addition through a controlled feedback mechanism. All the DGM processes are controlled by a specialised software that permits monitoring of all parts in real time (Mercuri et al., 2008;Wickham et al., 2009;Mercuri et al., 2011;Vardakou et al., 2011;Wickham et al., 2012). Material emptied from the DGM can be then processed within a simulation of the small intestine. ...
... To date, a limited number of pharmaceutical applications of the DGM have been reported in the literature. One study which explored the ability of the DGM to replicate the dynamic digestion of a self-emulsifying drug delivery system [SEDDS] suggested that the DGM provides a more accurate simulation of SEDDS digestion (at least in terms of droplet size) than conventional USP 2 apparatus (Mercuri et al., 2008). A second study assessed the relative performance of gelatin and HPMC capsules in the fed and fasted states. ...
Accurate prediction of the in vivo biopharmaceutical performance of oral drug formulations is critical to efficient drug development. Traditionally, in vitro evaluation of oral drug formulations has focused on disintegration and dissolution testing for quality control (QC) purposes. The connection with in vivo biopharmaceutical performance has often been ignored. More recently, the switch to assessing drug products in a more biorelevant and mechanistic manner has advanced the understanding of drug formulation behavior. Notwithstanding this evolution, predicting the in vivo biopharmaceutical performance of formulations that rely on complex intraluminal processes (e.g. solubilization, supersaturation, precipitation…) remains extremely challenging. Concomitantly, the increasing demand for complex formulations to overcome low drug solubility or to control drug release rates urges the development of new in vitro tools. Development and optimizing innovative, predictive Oral Biopharmaceutical Tools is the main target of the OrBiTo project within the Innovative Medicines Initiative (IMI) framework. A combination of physico-chemical measurements, in vitro tests, in vivo methods, and physiology-based pharmacokinetic modeling is expected to create a unique knowledge platform, enabling the bottlenecks in drug development to be removed and the whole process of drug development to become more efficient.
... 2,108,113 A mechanical gut model has been developed to simulate the complex flow profiles, dynamic secretions, and mechanical forces that occur in the human stomach by researchers at the Institute of Food Research (Norwich, UK). 114 Most researchers ignore droplet interactions with the surfaces of the stomach in their in vitro digestion models due to the inherent complexity of simulating the stomach's surface in the laboratory. Nevertheless, these interactions may be important in applications where the lipid droplets are designed to adhere to the stomach wall lining. ...
There is increasing interest in understanding and controlling the digestion of emulsified lipids within the food and pharmaceutical industries. Emulsion-based delivery systems are being developed to encapsulate, protect, and release non-polar lipids, vitamins, nutraceuticals, and drugs. These delivery systems are also being used to control the stability and digestion of lipids within the human gastrointestinal tract so as to create foods that enhance satiety and reduce hunger. In vitro digestion models are therefore needed to test the efficacy of different approaches of controlling lipid digestion under conditions that simulate the human gastrointestinal tract. This article reviews the current status of in vitro digestion models for simulating lipid digestion, with special emphasis on the pH stat method. The pH stat method is particularly useful for the rapid screening of food emulsions and emulsion-based delivery systems with different compositions and structures. Successful candidates can then be tested with more rigorous in vitro digestion models, or using animal or human feeding studies.
Responsible development of future foods requires in depth understanding of food digestion in the human body based on robust research models, ranging from in vitro models to randomized controlled human trials. This chapter overviews fundamental aspects of food digestion, namely bioaccessibility and bioavailability, and models mirroring gastric, intestinal, and colonic conditions. Second, the chapter demonstrates the potential of in vitro digestion models to help screen adverse effects of food additives, such as Titanium dioxide or carrageenan, or underpin the determinants of macro- and micronutrient digestion in different strata of the population, for example digestion of emulsions. Such efforts support rationalized design of functional foods, such as infant formulae, cheese, cereals and biscuits which are validated in vivo or in randomized controlled trials.
The human gut microbiota is widely considered to be a metabolic organ hidden within our bodies, playing a crucial role in the host’s physiology. Several factors affect its composition, so a wide variety of microbes residing in the gut are present in the world population. Individual excessive imbalances in microbial composition are often associated with human disorders and pathologies, and new investigative strategies to gain insight into these pathologies and define pharmaceutical therapies for their treatment are needed. In vitro models of the human gut microbiota are commonly used to study microbial fermentation patterns, community composition, and host-microbe interactions. Bioreactors and microfluidic devices have been designed to culture microorganisms from the human gut microbiota in a dynamic environment in the presence or absence of eukaryotic cells to interact with. In this review, we will describe the overall elements required to create a functioning, reproducible, and accurate in vitro culture of the human gut microbiota. In addition, we will analyze some of the devices currently used to study fermentation processes and relationships between the human gut microbiota and host eukaryotic cells.
Graphic abstract
Understanding the gastric digestion process is essential for evaluating the bioaccessibility of nutrients from food matrices. The objective of this study was to investigate the kinetics of disintegration and gastric emptying patterns in a 3D printed stomach (ARK ® ) with white rice as the study sample. Modified power exponential model was used to fit the gastric retention data and the average t 1/2 and t lag values of the solid fractions were found to be 109.22 ± 4.20 and 84.16 ± 5.72 min, respectively. During the disintegration process, the weight percentage of medium size particles (∼0.35 mm) was found to be higher at 30 and 60 min. Moreover, there was a sharp decrease in the percentage of fine particles (<0.125 mm) at 90 and 120 min. The ARK ® could effectively mimic the physiochemical process of the human stomach, providing promising insights for future studies on the development of novel and functional food products.
In recent years, there has been an increasing interest in the development of advanced in vitro digestion systems to study the fate of foods during digestion in the gastrointestinal (GI) tract. This is particularly important to understand the physiological effect of foods on human health and to develop healthy foods with desired functions. Here, the representative in vitro systems (testing devices) already reported in literature are summarized and critically reviewed. The gross GI morphology and anatomical structures in humans and rats those are likely to have considerable effect on food digestion are described. The motivations, ideas and mechanisms of the biomimic dynamic in vitro rat and human stomach-intestine devices are presented in particular to show where we are at in this field. Despite that the valuable scientific insights have been gained through the current in vitro GI models, none of them seen to have effectively mimicked the aspects of GI morphology and anatomy. These should be taken into account along with the related biochemical environments and peristaltic movements occurring in vivo, in order to show the way forward for the development of more realistic in vitro models.
Background: Food digestion rate and location within the gastrointestinal (GI) tract are important for human health. Ideally, food digestion studies should be performed in vivo but this is not always technically, ethically and financially possible. Thus, various in vitro digestion systems have been developed, from static mono-compart- mental to dynamic multi-compartmental models, to simulate food digestive behaviors within the GI tract. Scope and approach: In this review, food digestion process along the GI tract is briefly described. The current in vitro digestion systems with regards to the human GI physiology, and their advantages versus limitations in the understanding of various food digestion processes in the upper GI tract are critically discussed. There is an emphasis on the “near real” dynamic rat (DRSD) and human (DHSI) gastric-intestinal systems, which not only mimic the peristaltic movements and biochemical conditions found in vivo, but also incorporate the gastric morphology and anatomical structures.
Key findings and conclusions: Although some in vitro digestion systems reported in literature can be statistically correlated with certain perspectives of food digestion processes in vivo, many physiological, anatomical and geometrical factors that play important roles in determining the digestion rate and extent have been overlooked. The DRSD and DHSI are advantageous in terms of being able to resemble the gastric morphology and anatomy in the rats and humans, respectively. It is of importance that the upper GI anatomy and morphology along with the related biochemical environments and peristaltic movements occurring in vivo should be considered in the de- velopment of more advanced and biologically relevant in vitro digestion systems.
The aim of this study was to monitor the release of glucose and structural changes in Brazilian indica and Thai japonica rice during digestion in a human digestion simulator capable of simulating both mechanical and chemical food digestion. Chemical composition, cooking time, hardness, thermal properties and morphology of the grains were also investigated. The oral and gastro-small intestinal digestion led to the creation of open structures in the cooked rice endosperm due to hydrolysis by digestive enzymes and subsequent leaching of digested components. Indica cooked rice maintained its compact microstructure until the mid-small intestinal digestion phase, which agrees well with its slower starch hydrolysis. However, both types of rice had similar starch hydrolysis (%) at the end of the digestion period. Higher levels of amylose-lipid complexation and protein content in indica rice may have played a role in slowing down the release of glucose during digestion. The slower release of glucose during digestion of indica rice may reflect prolongation of satiety or the feeling of fullness after its consumption.
This chapter is divided into three sections, each presenting a different type of methodologies that are commonly used to study the link between food digestion and health. The first section focuses on in vivo methods, which are those that involve a living organism. The main types of epidemiological study design are presented, including observational and intervention studies. The relatively new field of nutritional epidemiology is further introduced, while animal studies are also briefly considered. The second section concerns in vitro experiments, which simulate digestive processes outside the body. The principles and practicalities of different static and dynamic in vitro models encountered in the literature are presented. Further, in silico approaches to digestion studies are discussed in the third section, with emphasis on developing understanding of digestive processes using numerical and computer techniques, with the aim to produce predictive models.
There has been a great deal of interest in adequately controlling digestibility of the ingested foods in the human digestive tract. Gastric digestion plays an important role in the process of food digestion, being strongly affected by both physical and chemical digestion processes. Over the last decade, the importance of in vitro gastric digestion models has been increasing, which is mainly attributed to superior applicability to various conditions as well as better reproducibility of experimental data. The authors developed a human gastric digestion simulator (GDS) that simplifies the antrum geometry and function. The major advantages of the GDS include quantitatively simulated gastric peristalsis and direct observation of the digestion behaviors of food particles in the gastric contents. In this review, we provide a brief overview of the findings obtained through a series of studies using the GDS. First, the current progress of in vitro gastric digestion studies is described. We next introduce the history and development of the GDS and findings on the digestion characteristics of representative foods and food models using the GDS. Further improvement of the GDS could potentially make it a useful tool for designing novel functional foods for which digestibility and release of nutrients and bioactives are well controlled.
A dissolution test is a comparative tool for measuring the in vitro performance of solid oral dosage forms, either as a surrogate for evaluating the in vivo drug absorption or in quality control of products. The use as a surrogate for in vivo evaluation is possible only when valid in vitro–in vivo correlation has been established for a product, and the use for quality control is based on the fact that dissolution can be affected by product compositions, crystal forms, and particle sizes of ingredients, manufacturing process, and scales. Dissolution results of the same product can be affected by many parameters for dissolution testing, including test apparatus, medium (compositions, pH, ionic strength, and aeration), volume, stirring speed, and vibration of test environment. Thorough studies must be conducted to develop and optimize a dissolution method during the product development cycle to ensure that data are reliable and meaningful. A properly developed dissolution method should have sufficient discriminating power to detect any significant changes in product or process, and it should be robust enough to allow normal variability in routine manufacturing and testing to avoid unnecessary rejection of products. Dissolution specifications should be set based on the data about all the batches that have provided acceptable pharmacokinetic or clinical results. Statistical analysis, including graphing and simulation analysis, is useful to examine if the proposed dissolution specifications are set properly.
In order to assess drug release from a digestible drug delivery system (DDS), it is important to simulate the relevant digestion processes as well as the dissolution process. Compared to commonly used dissolution models, digestion models are typically more complex, as they incorporate the digestive enzymes. This also renders these models suitable for the evaluation of food effects on drugs and dosage forms.
In this chapter, the human digestion processes are briefly described, followed by a description of the most commonly used digestion models including the pH-stat controlled lipolysis models, the Dynamic Gastric Model (DGM) and TNO gastrointestinal model (TIM-1). The pH-stat controlled models are examples of relatively simple digestion models commonly used to evaluate the amount of drug solubilised in the aqueous phase during digestion of lipid based DDS (LbDDS), whereas the DGM and the TIM-1 represent two of the more complex dissolution and digestion models available. Emphasis will be on the models suitability to assess LbDDS and will therefore primarily involve lipid digestion.
A novel in vitro gastric device, the Gastric Digestion Simulator (GDS), was developed for the direct observation and quantitative analysis of the food digestion process in the human stomach. In addition to simulating the chemical digestion environment, this device provides a physical digestion environment comparable to that found in the stomach by simulating peristalsis, which is assumed to contribute to solid food disintegration. The GDS was successfully used to directly observe the disintegration process of Tofu (bean curd) as a typical solid food containing protein. The size distribution and protein content of Tofu particles during the digestion experiments were investigated. The results demonstrated the difference in particle disintegration between GDS and flask shaking experiments, which may be due to the lack of peristalsis in the latter case. Moreover, the size distribution of Tofu particles after the GDS experiments was affected by the physical properties of Tofu, thus revealing the usefulness of GDS for food digestion analysis.
This study quantitatively analyzed the flow phenomena in model gastric contents induced by peristalsis using a human gastric flow simulator (GFS). Major functions of the GFS include gastric peristalsis simulation by controlled deformation of rubber walls and direct observation of inner flow through parallel transparent windows. For liquid gastric contents (water and starch syrup solutions), retropulsive flow against the direction of peristalsis was observed using both particle image velocimetry (PIV) and computational fluid dynamics (CFD). The maximum flow velocity was obtained in the region occluded by peristalsis. The maximum value was 9 mm s(-1) when the standard value of peristalsis speed in healthy adults (UACW = 2.5 mm s(-1)) was applied. The intragastric flow-field was laminar with the maximum Reynolds number (Re = 125). The viscosity of liquid gastric contents hardly affected the maximum flow velocity in the applied range of this study (1 to 100 mPa s). These PIV results agreed well with the CFD results. The maximum shear rate in the liquid gastric contents was below 20 s(-1) at UACW = 2.5 mm s(-1). We also measured the flow-field in solid-liquid gastric contents containing model solid food particles (plastic beads). The direction of velocity vectors was influenced by the presence of the model solid food particle surface. The maximum flow velocity near the model solid food particles ranged from 8 to 10 mm s(-1) at UACW = 2.5 mm s(-1). The maximum shear rate around the model solid food particles was low, with a value of up to 20 s(-1).
The complex process of oral drug absorption is influenced by a host of drug and formulation properties as well as their interaction with the gastrointestinal environment in terms of drug solubility, dissolution, permeability and pre-systemic metabolism. For adult dosage forms the use of biopharmaceutical tools to aid in the design and development of medicinal products is well documented. This review considers current literature evidence to guide development of bespoke paediatric biopharmaceutics tools and reviews current understanding surrounding extrapolation of adult methodology into a paediatric population. Clinical testing and the use of in silico models were also reviewed. The results demonstrate that further work is required to adequately characterise the paediatric gastrointestinal tract to ensure that biopharmaceutics tools are appropriate to predict performance within this population. The most vulnerable group was found to be neonates and infants up to 6months where differences from adults were greatest.
The digestion and metabolism of lipids continues to generate considerable scientific interest, with food emulsions increasingly being seen as a mechanism by which lipid uptake may be controlled. Scientific advancement in this field is partly being driven by the ongoing need to address the obesity crisis, for which the enhancement of satiety and/or reduction of energy intake is seen as a positive solution in achieving more effective weight management. Yet the ability to regulate lipid uptake is also seen as beneficial in other areas, such as improved nutrition for the young and/or elderly and in cardiovascular protection.
This chapter provides the reader with some basic considerations relating to the purpose, aims, goals, development and validation
of an in vitro drug release test for a modified release oral product in order to maximize its successful research, optimization
and development.
This paper uses computational fluid dynamics to simulate and analyze intragastric fluid motions induced by human peristalsis.
We created a two-dimensional computational domain of the distal stomach where peristalsis occurs. The motion of the gastric
walls induced by an antral contraction wave (ACW) on the wall of the computational domain was well simulated using a function
defined in this study. Retropulsive flow caused by ACW was observed near the occluded region, reaching its highest velocity
of approximately 12mm/s in the narrowest region. The viscosity of the model gastric contents applied in this study hardly
affected the highest velocity, but greatly affected the velocity profile in the computational domain. The shear rate due to
gastric fluid motion was calculated using the numerical output data. The shear rate reached relatively high values of approximately
20s−1 in the most occluded region. The shear rate profile was almost independent of the fluid viscosity. We also simulated mass
transfer of a gastric digestive enzyme (pepsin) in model gastric content when peristalsis occurs on the gastric walls. The
visualized simulation results suggest that gastric peristalsis is capable of efficiently mixing pepsin secreted from the gastric
walls with an intragastric fluid.
KeywordsPeristalsis-Flow-field-Shear force-Mass transfer-CFD
In recent years there has been an increasing interest in the development of new and efficient oral food delivery systems as tools to prevent disease and promote human health and well-being. Such vehicles are sought to protect bioactive ingredients added to food while controlling and targeting their release as they pass through the human gastrointestinal tract (GIT). This review aims to summarize the key concepts of food delivery systems, their characterization and evaluation. Particularly, evaluation of their performance within the human GIT is discussed. To this end an overview of several in vivo and in vitro methods currently applied for the study of such systems is given. Although considered to be still in its infancy, this promising field of research is likely to infiltrate into real products through rational design. In order for such efforts to materialize into real products some challenges still need to be met and are discussed herein. Overall, it seems that adopting a comprehensive pharmacological approach and relevant cutting edge tools are likely to facilitate innovations and help elucidate and perhaps tailor delivery systems' behavior in the human GIT.
ResearchGate has not been able to resolve any references for this publication.