Dietary titanium dioxide (E171) increases systemic ROS levels and alters the colon transcriptome – Evidence from a human dietary intervention study

This study provides critical insights into the adverse effects of titanium dioxide (E171) on human gastrointestinal health and its potential molecular mechanisms of action, marking a significant advancement in food toxicology. Through a human dietary intervention study involving 31 participants consuming 2 mg/kg body weight/day of E171 in yogurt, the research confirmed compliance by detecting significantly elevated titanium levels in feces during the intervention. Importantly, the study identified a statistically significant increase in superoxide radicals in whole blood, indicating that E171 induces oxidative stress. While systemic inflammation markers, including cytokine levels and hs-CRP, showed no relevant changes, gene expression analysis of colon biopsies revealed substantial transcriptomic alterations. Specifically, 73 enriched pathways were identified, including those related to metabolic reprogramming (consistent with the Warburg effect), colorectal cancer development, ribosome biogenesis, PPAR signaling, and chemical carcinogenesis involving reactive oxygen species. Additionally, the characterization of E171's physicochemical properties post-gastrointestinal digestion provided a clearer understanding of nanoparticle exposure in the human gut. This study is novel as it delivers human-specific data, bridging a critical gap in the knowledge of E171's health risks. It also provides molecular evidence linking its consumption to hallmarks of colorectal cancer. These findings support the European Union's decision to ban E171 as a food additive and highlight its potential risks, contributing significantly to food toxicology.