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Objective  Up to 44% of particulates of food-grade titanium dioxide (TiO 2 ) are in nanoscale, while the effect and combined effect of which with other substances on intestinal barrier haven’t been fully understood yet. This study is aimed to study the effect of two kinds of TiO 2  nanoparticles (TiO 2  NPs and TiO 2  MPs) on intestinal barrier functions, to reveal the combined effect of TiO 2  NPs and Lipopolysaccharide (LPS) on intestinal barrier.    Methods  Male ICR mice were randomly divided into 18 groups (3 feed types * 3 exposure length * 2 LPS dosage) and were fed with normal or TiO 2 -mixed feed (containing 1% (mass fraction, w/w) TiO 2  NPs or TiO 2  MPs) for 1, 3, 6 months, followed by a single oral administration of 0 or 10 mg/(kg body weight) LPS. Four hours later, the transportation of TiO 2 , the intestinal barrier functions and the inflammatory response were evaluated.    Results  Both TiO 2  notably increased the intestinal villi height / crypt depth ratios after 1 and 3 months of exposure, and increased the expression of ileal tight junction proteins (ZO-1 and occludin) after 1 month of exposure. After 6 months of exposure, TiO 2  NPs led to reduced feed consumption, TiO 2  MPs caused spare microvilli in small intestine and elevated Ti content in the blood cells. The intestinal permeability didn’t change in both TiO 2  exposed groups. After LPS administration, we observed altered intestinal villi height / crypt depth ratios, lowered intestinal permeability (DAO) and upregulated expression of ileal ZO-1 in both (TiO 2  +LPS) exposed groups. There are no significant changes of ileal or serum cytokines except for a higher serum TNF-α level in LPS treated group. The antagonistic effect was found between TiO 2  NPs and LPS, but there are complicated interactions between TiO 2  MPs and LPS.    Conclusion  Long-term intake of food additive TiO 2  could alter the intestinal epithelial structure without influencing intestinal barrier function. Co-exposure of TiO 2  and LPS would enhance intestinal barrier function without causing notable inflammatory responses, and there is antagonistic effect between TiO 2  NPs and LPS. All the minor effects observed might associate with the gentle exposure method where TiO 2  being ingested with feed.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12989-021-00399-x.

particle and fibre toxicology

The combined effect of food additive titanium dioxide and lipopolysaccharide on mouse intestinal barrier function after chronic exposure of titanium dioxide-contained feedstuffs