The food colorant E171 (TiO2) containing nano fractions can cause potential health problems. In the presented work, we used a “gastrointestinal tract” model (oral→large intestine) to “digest” a fruit smoothie in the presence of TiO2 nanoparticles and the Lactiplantibacillus plantarum B strain. The TiO2 migration was measured using the microfiltration membrane (0.2 μm; model of “TiO2 bioacessability”). We observed that the addition of the smoothie reduced the Ti content in the microfiltrate (reduced “bioacessability”) at the “mouth”, “stomach” and “large intestine” stages, probably due to the entrapment of Ti by the smoothie components. A significant decrease in Ti “bioaccessibility” at the “gastric” stage may have resulted from the agglomeration of nanoparticles at a low pH. Additionally, the presence of bacterial cells reduced the “bioaccessibility” at the “large intestine” stage. Microscopic imaging (SEM) revealed clear morphological changes to the bacterial cells in the presence of TiO2 (altered topography, shrunk-deformed cells with collapsed walls due to leakage of the content, indentations). Additionally, TiO2 significantly reduced the growth of the tested bacteria. It can be stated that the interactions (most probably entrapment) of TiO2 in the food matrix can occur during the digestion. This can influence the physicochemical properties, bioavailability and in vivo effect of TiO2. Research aimed at understanding the interactions between TiO2 and food components is in progress.