The TIM technology is used to get consistent and reliable scientific data about the behavior of your oral products during transit through the stomach, the small intestine and large intestine. Twenty years of experience with dynamic gastrointestinal simulation and performance of evaluation studies in comparison with clinical studies guarantees the predictive quality of the results for a broad range of TIM research applications. The TIM-1 and tiny-TIM systems simulate the successive dynamic conditions in the stomach and small intestine, TIM-2 in the large intestine.
TIM studies quickly and cost-efficiently provide reliable information about the gastro-intestinal digestion of your products and subsequent release, stability, and bioaccessibility of the compounds of interest. Studies can be performed under simulated human and animal GI conditions related to different types of drinks and meals, age and health status. This information enables better informed decisions to be made, minimizing the number of subsequent animal experiments and clinical studies.
The multi-compartmental, computer-controlled TIM-1 system accurately simulates the successive dynamic human conditions or animal conditions in the stomach and the three parts of the small intestine: duodenum, jejunum, and ileum. These conditions are responsible for the digestion of food and the release and dissolution of nutrients, bioactive compounds, and pharmaceutical ingredients. Dissolved low molecular weight compounds are dialyzed or filtrated from the jejunum and ileum compartments. Samples collected during the experiments are analyzed for the respective compounds. These data give an accurate insight in the total and time-related availability for absorption of nutrients and drugs.
The tiny-TIM system simulates the successive dynamic human conditions (adults and children) or animal conditions in the stomach and small intestine. It has, however, one compartment for the small intestine in which the intestinal passage is mimicked (in contrast to TIM-1, which has separate compartments for the duodenum, jejunum and ileum).
Tiny-TIM has been successfully evaluated for research applications for food and nutrition, pet food , animal feed and pharmaceutics (including pediatrics). In line with TIM-1, tiny-TIM has a high predictive value for clinical data, but it should be noted that tiny-TIM gives less detailed information compared with TIM-1. An advantage of the tiny-TIM system is that two parallel experiments can be performed at the same time by one operator which saves time and costs.
The TIM-2 system simulates the large intestine (colon). This includes high-density, metabolic active microbiota of human (e.g. adult or children, healthy or diseased) or animal origin under strict anaerobic conditions. The composition of the microbiota in TIM-2 is stable over a long term, as measured with DNA technologies. This is realized by accurate simulation of the colon conditions, such as temperature, pH control, peristalsis, the supply of non-digested food compounds as substrates for the microbiota, and continuous filtration of the microbial metabolites and water that are produced. This enables the effect of a test product (e.g. prebiotics or a colon-targeted drug) on the microbiome and vice versa to be measured. Besides measurements of the microbiome using DNA technologies metabolites produced by the microbiome are also measured using Triskelion’s analytical platforms. At least three experiments (for example, a duplicate experiment with the test product and one blank experiment) are performed in parallel. This enables a direct and reliable analysis of the effect of the test product on the microbiome compared to the blank experiment with identical start compositions of the microbiome. The throughput performance is relatively high in contrast to other in vitro dynamic colon systems.
Application for human food and nutrition
The TIM systems have been evaluated and applied for a broad range of human nutrition studies, related to food quality, functional foods and food safety. Examples of the different applications in food and nutrition research are described in more than 150 publications.
The main applications of the TIM systems in food and nutrition research measure:
- digestion of (fortified) foods, food ingredients and supplements;
- availability for intestinal absorption (bioaccessibility) of nutrients.
The quality of protein is measured in TIM on the digestibility and bioaccessibility of (indispensable) amino acids, which can be expressed as PDCAAS and DIAAS.
The digestibility of carbohydrate, expressed as glycemic load and glycemic response, is measured in TIMcarbo. This is a combined technology of tiny-TIM, brush border enzymes and computer simulation for insulin response.
The digestibility of fat and the bioaccessibility of fatty acids, including EPA and DHA, are determined in TIM with a lipophylic membrane.
Besides the macro-nutrients, the bioaccessibility of micro-nutrients, such as minerals, and water- and fat-soluble vitamins can also be determined by TIM.
Besides food quality studies, TIM is also used to investigate:
- release and survival of probiotics and food-borne pathogens;
- (lack of) digestion and colon fermentation of dietary fibers and prebiotics
- bioaccessibility and colon metabolism of phytochemicals (botanicals);
- digestion increasing compounds, e.g. exo-lipase and exo-proteinase;
- digestion inhibiting compounds, e.g. enzyme inhibitors, fat/cholesterol binders.Food safety
Occasionally, TIM studies are performed to get insight into the:
- lack or rate of digestibility of (potential) food allergens for infants and adults;
- release, stability and bioaccessibility of (potential) toxic compounds, including
- unintended oral intake of compounds (e.g. cosmetics, soil);
- binding of (potential) toxic compounds, e.g. mycotoxins, phosphate in kidney disease patients.
Application for pet food and animal feed
The TIM systems have been evaluated and applied for various pet food and animal feed studies, simulating species specific animal GI conditions, related to food/feed quality, functional compounds and safety.
The main applications of TIM in pet food and animal feed research focus on the:
- digestion of pet food and animal feed and food/feed ingredients;
- availability for intestinal absorption (bioaccessibility) of nutrients;
- effect of food/feed processing on digestion.
The quality of protein is measured in TIM as true ileal digestibility and bioaccessibility of (indispensable) amino acids. These studies give more information on the limiting amino acids than in vivo growth studies, e.g. Protein Efficiency Ratio. The digestibility of fat and carbohydrate are investigated in TIM to determine the quality and available energy.
Examples of applications of TIM in functional animal food/feed research are the efficacy of:
- plant extracts on improvement of digestion;
- exo-enzymes on the bioaccessibility of nutrients, e.g. phytase added to feed for the bioaccessibility of phosphate from phytate.
TIM can also be used to investigate:
- binding of mycotoxins in contaminated feed compounds;
- anti-nutritional factors in raw materials and after processing.