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TIM gastro-intestinal model refined further

Published: 12-11-2015, | Member: Triskelion

Triskelion’s latest equipment makes it possible to determine the digestibility and availability for absorption of nutrients and food products. Micro TIM and TIM-AGC, the latest additions to TNO’s gastro-intestinal model (TIM), have further refined this dynamic human digestion model and for example allow studies on gastric viscosity.

The food industry’s demands keep changing, as Triskelion knows from experience. The company responds to these market developments by developing new technologies. “Products made with nano particles as ingredients are one of these developments. Food manufacturers want to know how such products behave in the gastro-intestinal tract,” says Susann Bellmann, Project Manager for in vitro Gastro-Intestinal Research at Triskelion. “Our existing TIM systems were not able to answer these questions, so we developed a new version called Micro TIM which is suitable to study compounds that exist is very small quantities. These can be nano particles, but also allergens or new pharmaceutical chemical entities.”

Since the 1990s the gastro-intestinal model (TIM) has been able to provide insight into the fate of food and pharmaceutical products whilst travelling through the gastro-intestinal tract. TIM makes it possible to study the digestibility of food and food components, and to determine the availability for absorption of e.g. proteins, fats, minerals or vitamins. The model can also compare the release of an active pharmaceutical ingredient in medical formulations. The computer controlled models use dynamically regulated parameters as occurring in the human gastro-intestinal tract. This includes for example the body temperature, peristalsis, variable changing pH values, realistic secretion of bile and digestive enzymes as occurring in the stomach and small intestine.

TIM is a collective term that covers various systems. TIM-1, TIM-2 and tiny-TIM have been around for several years. The latest addition to the TIM family is a down-sized TIM system, nick named Micro-TIM. Also the TIM-1 and tiny-TIM can now be equipped with the advanced gastric compartment (TIMagc) in the place of the current gastric compartment. Among others, it allows to measure gastric viscosity online.

Dynamic models
There is meanwhile over 20 years of experience testing food products and pharmaceuticals using the TIM gastro-intestinal models. Bellmann explains: “This computer-controlled system is very sophisticated, because it mimics the dynamically changing conditions as they occur in e.g. healthy adults. But it can also be set to mimic deviating conditions of for example diseased individuals, such as of patients with cystic fibrosis. In contrast, static in vitro digestion methods are not able to mimic these dynamically changing conditions and for that reason are less predictive for the in vivo situation. The results obtained from the TIM-system are highly reproducible, which is difficult to achieve in vivo because of the natural biological inter-individual variability. This variability makes it sometimes difficult to identify effects of the products under investigation and thus TIM can be a useful tool to elucidate these effects. For many studies, TIM is also an alternative to animal testing.”

TIM-1 was the first system developed to simulate the gastro-intestinal tract. The system consists of one compartment that mimics the stomach and three compartments that mimic the small intestine: the duodenum, jejunum and ileum. This enables TIM-1 to accurately study the digestibility and availability for absorption (bio accessibility) of nutrients of complex meal matrices or single ingredients. However, “In practice, it wasn’t always necessary to use such an elaborated system with three small intestinal compartments,” Bellmann explains. “So a more simplified model was developed, the tiny-TIM system. This system has one small intestinal compartment, which mimics average small intestinal conditions. As a result it has less sampling points and several experiments can be performed simultaneously. As special application, this system was validated to simulate infant conditions and is frequently used to test newly developed infant formulas.”

To investigate what happens to products in the large intestine (colon), the TIM-2 system can be used. In this system colon fermentation, of non-digested products are studied. These can be dietary fibers (prebiotics) or effects of probiotics that survived the passage through the upper gastro-intestinal tract on the microbiota composition. An active and viable microbiota (bacteria) is present, this can be of human origin or e.g. from animals such as dogs or pigs for animal fermentation studies.

New questions
Most of the time TIM is used for contract research for the food and pharmaceutical industries, according to Martin Ham, Business Development Manager at Triskelion. But the feed industry is a regular customer, too. “Lately, we’re getting more requests concerning substances that can be extracted from waste streams, like protein,” says Ham. “One example is residues from the wine industry. It’s possible to extract very promising components (e.g. phytochemicals) from grape skins, but that prompts the question: are these available for absorption for the human body?”

Another new question is that food manufacturers looking to test products on their allergenic potency. This made it necessary to further refine the TIM system. Bellmann explains: “Food allergens exist in miniscule amounts, which are not traceable in our existing systems. That’s why down-sized version was developed. This version is 90 times smaller than TIM-1, so we nick-named it micro-TIM.” Ham adds: “Micro-TIM offers extra possibilities, namely it can also be used to test the behavior of nano particles contained in food products.”

Improved stomach
About a dozen of TIM systems are installed at companies, universities and research institutions worldwide and the resulting community of TIM Users, the TIM User Group, meets every two years. As Martin Ham says: “Those meetings are useful so much for feedback and exchanging experiences One of the things users found was that the TIM stomach compartment sometimes does not answer all research questions and based on information exchange of user ‘s requirements the agc was developed. We’re currently at the validation stage, so we’re almost there.”