Dietary Titanium Dioxide (E171) Alters the Colon Transcriptome-Evidence From a Human Dietary Intervention Study

Food-grade titanium dioxide (E171) has been removed from the European food market due to concerns about its potential genotoxicity, yet human evidence remains limited. Given its continuous use outside the European Union, clarifying its potential hazard is essential for human risk assessment. In a randomized crossover study, 31 adults consumed 2 mg/kg body weight/day of E171 for 2 weeks, with biospecimens collected after both control and exposure periods. Oral intake resulted in elevated titanium concentrations in feces (CTRL: 6.3 mg/kg; E171: 377 mg/kg). Particle characterization showed a median size of 228 nm, with 9% <100 nm. Systemic oxidative stress increased, evidenced by increased superoxide radical levels in whole blood (p = 0.057). Transcriptomic profiling of colon biopsies revealed activation of 73 pathways linked to oxidative stress, cellular metabolism, and colorectal cancer-associated processes. The observed transcriptional changes were consistent with findings of its proposed mode of action. This human intervention study characterizes the effects of dietary E171 following human gastrointestinal digestion and provides evidence that exposure to dietary E171 induces systemic oxidative stress and transcriptional changes in the colon. These findings strengthen regulatory concerns about E171 as a food additive and its potentially harmful effects on human gastrointestinal health.