Effects of Food-Grade Titanium Dioxide (E171) on Physicochemical Properties, ROS production, and Microbiome in the TIM-2 Model
Food-grade titanium dioxide (E171) has been a common food additive used for its whitening and opacifying properties. However, recent studies have raised concerns about its potential adverse effects on gut health, potentially mediated by its interactions with the human microbiome. In this study, we employed the TIM-2 in vitro model, which simulates the human colon, to investigate the physicochemical properties of E171 in the large intestine and its impact on microbiome composition and metabolic activity, in both fasted (E171-aq) and fed (E171-yog) states. We focused on particle size distribution of E171, reactive oxygen species (ROS) formation, microbiome abundance, and production of short-chain fatty acids (SCFAs). Particle size analysis revealed that E171 formed larger aggregates in the fasted state with 210 nm in size but decreased in size when digested in the fed state in yogurt, resulting in aggregates of 167 nm, with an increasing fraction of nanoparticles over time of up to 20%. Notably, E171 did not produce ROS following fermentation in the TIM-2 model. SCFAs analysis demonstrated a marked increase in butyrate levels following E171 exposure, raising concerns about a potential metabolic shift within the commensal gut microbiome. Microbiome analysis through 16S rRNA amplicon sequencing showed alterations in bacterial composition, including a decrease in Blautia and an increase in Lachnospiraceae for both E171-aq and E171-yog exposed groups, which can be a potential indicator of increased inflammation. In conclusion, this study highlights physicochemical changes of E171 when it is digested in the TIM-2 model. E171-yog showed decreased aggregation size and an increased fraction of nanoparticles, compared to E171-aq. E171 showed the potential to alter human gut microbial composition and function, mainly through elevated butyrate production, which may have implications for gut health. These findings underscore the need for further investigation into the long-term effects of E171 consumption, especially in the context of different dietary states.