Quality in Relation to Other Models with the Same Applicability

Compared to other in vitro models mimicking the colon, TIM-2 has a number of features that are unique (see Sect. 26.1.2) and that allow to predict what would happen in a clinical trial. In the previous section the example of lactulose was given. To validate these results one would need to sample the proximal colon, which is only possible when using a long catheter that is inserted through the nose or throat and reaches the proximal colon (Venema 2011), or a tube that is stuck up the rectum to reach the proximal part of the large intestine. Although this has been done, it is very invasive and it is difficult to get ethical approval for testing functionality of numerous food components. Nevertheless, it is our belief that the results that were found in TIM-2 predict what happens in vivo, even though this could not be confirmed because the analytes in fecal matter in this case were not representative for those produced in the proximal colon, as they had all been absorbed by the colonic tissue during transit from proximal to distal colon, which may take anything from 24 to 72 h.

One of the reasons the system can predict what happens in real life so well is the presence of the dialysis system. As discussed above, this system prevents the accumulation of microbial metabolites, which normally are also taken up by the gut epithelium. In other systems metabolites tend to accumulate. Apart from slowing down or stopping further microbial breakdown of the substrates under study (Ramasamy et al. 2014), both the kinetics and true production of e.g., SCFA are inaccurate in these incubations. Since the metabolites are not removed, this allows for them to be converted into one another. For example, two molecules of acetate can be coupled to form butyrate, while lactate can be converted to propionate or butyrate. While this normally occurs to a certain extent in the gut microbiota, and is called cross-feeding (Kovatcheva-Datchary et al. 2009), in batch incubations this happens to a degree that is no longer physiological.

Also, the accumulation of the SCFA (in particular) leads to the inhibition of certain members of the microbiota, certainly if this is accompanied by a drop in pH. Because of this, the composition of the microbiota may change and no longer reflect that of the normal gut. It should be said that even in TIM-2 the microbiota will change after introduction of the inocula (Rajilic-Stojanovic et al. 2010).

Due to the fact that the system closely mimics physiological parameters, the experiments in TIM-2 usually take 1 week (see Sect. 26.2). In contrast, other models that mimic the large intestine usually take several weeks due to the need to reach steady state. Since multiple units of TIM-2 can be run at the same time (maximally 10), comparisons with a control can be made and steady state in TIM-2 is not strictly required. For a more extensive review of TIM-2 in comparison to other in vitro models mimicking the colon, please refer to Venema and van den Abbeele (2013).

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