Elucidating metabolic dysfunction induced by titanium dioxide in intestinal epithelial cells using an integrative...

Titanium dioxide (TiO₂) is widely present in a variety of food and personal care products, leading to frequent human exposure primarily via oral ingestion. Although the oral bioavailability of TiO₂ nanoparticles is generally considered low, the gastrointestinal tract represents the primary site of exposure and may undergo local molecular and metabolic disturbances following repeated contact.

In this study, we investigated the impact of TiO₂ exposure on gene expression and cellular metabolism in intestinal epithelial cells using integrated transcriptomic and metabolomic approaches.

Transcriptomic analysis identified differentially expressed genes associated with disruptions in cellular components, molecular functions, and biological processes, collectively pointing to mechanisms underlying TiO₂-induced cytotoxicity. Metabolomic profiling further revealed that TiO₂ exposure perturbed key metabolic pathways, as evidenced by significant alterations in critical metabolites-including acetylcholine, glutathione, cytosine, deoxyadenosine, and pantothenic acid-indicative of broad metabolic dysfunction. Notably, integrative correlation analysis demonstrated that TiO₂ disrupts lipid metabolism, amino acid metabolism, nucleotide metabolism, energy metabolism, and redox homeostasis.

In conclusion, our findings elucidate the metabolic mechanisms driving TiO₂-induced intestinal toxicity. Moreover, this work underscores the power of integrated transcriptomic-metabolomic analysis as a robust strategy for mechanistic toxicological evaluation and risk assessment of nanomaterial exposure.