What is the TIM-2 system? An in-vitro model of the colon

April 8th, 2022

The TIM-2 model is a dynamic gastrointestinal model, which is used for in-vitro research. The TIM-2 model can be used to study changes in the microbiota composition and the production of beneficial molecules in the gut. It resembles the human large intestine, including peristalsis, dialysis, and microorganisms. It is a good model that provides short experiment durations and the studies done with it are highly reproducible.

TIM-2 in-vitro-gastrointestinal-model

What is the TIM-2 model?

The TIM-2 (TNO in-vitro) model is a computer-controlled dynamic in-vitro gastrointestinal model of the colon used in research to study changes in the microbiota composition.

This model closely mimics part of the human large intestine, including its microorganisms, peristaltic movements, temperature (37ºC) and acidic pH (5.8).

What is the TIM-2 model used for in research?

The TIM-2 model has a wide range of applications in research. It can be used to study changes in the microbiota composition and production of beneficial molecules such as short-chain fatty acids associated with specific dietary patterns or ingredients and, consequently, to increase human health through the understanding of microbiota.

Due to the health benefits of short-chain fatty acids (SCFA), many studies have focused on carbohydrate fermentation and the subsequent production of SCFA.

However, it has also been used to study the effects of probiotics after antibiotic treatment, fermentation of prebiotic fibres, metabolization of molecules such as flavonoids and even to investigate the differences in microbiota from lean and obese individuals.

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Difference between TIM-2 model and other in-vitro models

Compared to other in-vitro models, TIM-2 holds some unique features, which allow predicting what would happen in an actual clinical trial.

The way the peristaltic movements are produced in the TIM-2 model gives a better mixing of the components than what would be accomplished by stirring or shaking. Thanks to this, in TIM-2 there is no phase-separation of solids and liquids, which is what occurs in other models.

On the other hand, in vivo microbial metabolites are normally taken up by the gut epithelium. This is, of course, not possible in an in-vitro model, but the TIM-2 model features a unique dialysis system that removes these metabolites produced by microorganisms.

The accumulation of these microbial metabolites would otherwise result in the inhibition or death of the microorganisms present in the model. Therefore, the dialysis system allows maintaining a highly active microbiota, with a similar density to that found in the human intestine.

In other systems, metabolites tend to accumulate. In fact, with the TIM-2 model, since all the microbial metabolites are collected, they can be measured, which is something not possible in a real-life setting.

What are the advantages and limitations of the TIM-2 model?

Advantages of the TIM-2 model include:

Short experiment duration. Compared to other models, experiments are quick, usually taking three test days or even less.

Presence of peristaltic movements and dialysis system. These two unique features allow predicting what would happen in an actual clinical trial.

Single parameter study. If a single parameter in the system is changed, the effect of that parameter on the microbiota can be studied.

Highly reproducible. Since the model is computer-controlled, it is highly reproducible.

Like other in-vitro models, the TIM-2 model has some limitations, which include:

Absence of gut epithelial cells, immune cells and neurons. However, samples can be taken and incubated with these kinds of cells to investigate interactions.

Based mostly on healthy individuals. The model has been developed based on data coming from mostly healthy individuals. For this reason, it is unclear exactly which parameters to adjust when simulating patient populations.

Absence of feedback mechanisms. Due to this, as with similar in-vitro models, the results will always be an indication of what may occur in real life and, therefore, they should be interpreted carefully.