TIM

Our products pass through gastrointestinal tract, so digestion and gut microbiology are important areas for us to understand.

Did you know?

• Length of our GI tract growths from 1,5m as baby to more than 6 meter as an adult
• The small intestine begins at the duodenum, which receives food from the stomach. Length = usually between 3-5 m long
• The surface area of the human small intestinal mucosa, due to enlargement caused by folds, villi and microvilli, averages 30-40 square meters (m2).
• This is 20 times compared to skin surface area = 2 square meter
• It also contains 100 trillion bacteria;
• That is more than 10x the amount of human cells
• These bacteria weigh approx. 2 kg
• Actually, 70-80% of our immune cells are in our gut. So in other words: we are walking and talking ecosystems!

What is TIM

• TIM officially stands for TNO In vitro Model but is also called TNO Intestinal Model.
• Our products pass through the gastrointestinal tract, so digestion and gut microbiology are important areas for us to understand.
• TIM is a computer controlled dynamic gastrointestinal model. It simulates absorption and to a small degree also digestion processes.
• It is quite a unique model, which is only available at a few locations worldwide (approx. 20),.
• TIM was developed by Nutricia Research together with TNO in the early 1990’s. Over the years, this model has been updated and improved.

How TIM works

• TIM is computer controlled and we’re able to simulate digestion in infants, adults, patients and elderly. Digestion in babies is for instance different from digestion by elderly. Elderly, generally speaking, have a delayed gastric emptying and slower acidification of the stomach.
• We can change parameters as ph degree and enzymes which differs in infants and elderly.
• From clinical literature we read the conditions of a specific population. Normally babies and infants show a high ph degree and few enzymes. On different levels we can control the level of ph degree and enzymes for both the stomach and the smaller intestines.
• Temperature: normal body temperature
• The yellow clamps or scissors are places where we can take samples while it is running at various part of the GI tract to understand “what is going on” during the digestive process.
• TIM actually allows us to take samples in more places than possible in humans.
• Doesn’t allow studying gut microbiota (as only represents stomach and small intestine), other models for these studies. There is oxygen “in Tim”, so gut microbiota cannot be placed I there, it would overgrow the whole system.
• TIM can have a maximum of two runs per week. After a one run (approx. 6 hours) it has to be thoroughly cleaned, which takes 2 days
• Requires much expertise from the operator

What we study with TIM

• What we really want to know before we go into clinical trial is: how is a product behaving in the human. TIM is a model that comes close to in vivo. With TIM it is easy to see what happens – for example does medical nutrition clod? And timing: how long does it take for nutrition to leave the stomach?
• Different examples of research we do with TIM:

1. The medical division used the TIM to improve our tube feeds in critical care. Quick emptying the stomach is important for tube feeding to avoid retention. Delayed gastric emptying, which can be present in many patients, leads to increased stomach content, which can lead to reflux, vomiting and even worse aspiration (stomach content in the lungs).
   • Different proteins behave differently in speed and slower proteins like casein tend to cause cluttering.
   • Non-coagulation leads to faster gastric emptying times. It is known that casein (normally a dominant protein) based formulas coagulate in the stomach, which may impair gastric emptying. For that reason, we developed a new protein blend for our tube nutrition, based on less casein and adding soy and pea proteins.
   • With help of, amongst other, the TIM model, we found that this new protein blend did not coagulate, in contrast to more dominant casein based nutrition. Furthermore, we were able to show with the TIM model that this new protein blend yielded faster gastric emptying of protein. As such the new protein blend may help to reduce gastro intestinal complications.
2. Besides speed of protein we also study when proteins are broken down; is that in the stomach? Do we want the proteins to survive the stomach? If they die already in the stomach what do we need to do to keep them alive in the intestines?
3. To what respect and with what speed are macro nutrients like carbohydrates and fats digested and taken in by the body?
4. Or how do micronutrients like minerals and vitamins survive the gastrointestinal tract?
5. Or studies that involved tube feeding after the stomach (naso-duodenal feeding) for example after surgery.
6. Or which part of a meal is indigestible and will pass through to the colon. Over there it could influence the composition and function of the residing microbiota. Typically dietary fibres will be indigestible, but these are not the only nutrients that pass over.

Lab behind TIM

• Behind TIM there is the microbiology lab, including a culture collection of hundreds of different probiotics.
• We analyze the survival of probiotic bacteria in the upper GI, as it is commonly hypothesized that probiotic bacteria need to reach the colon alive in order to induce beneficial effects.
• You see more simplified models gastrointestinal models like the SIM, (Semi-dynamic In vitro Model of gastrointestinal tract), which includes 8 reactors in parallel, so the digestion of 8 foods can be studied in one experiment.