In an early study Jani et al. administred rutile TiO₂ (500 nm) as a 0.1 ml of 2.5 % w/v suspension (12.5 mg/kg BW) to female Sprague Dawley rats, by oral gavage daily for 10 days and detected presence of particles in all the major gut associated lymphoid tissue as well as in distant organs such as the liver, spleen, lung and peritoneal tissue, but not in heart and kidney. The distribution and toxicity of nano- (25 nm, 80 nm) and submicron-sized (155 nm) TiO₂ particles were evaluated in mice administered a large, single, oral dosing (5 g/kg BW) by gavage. In the animals that were sacrificed two weeks later, ICP-MS analysis showed that the particles were retained mainly in liver, spleen, kidney, and lung tissues, indicating that they can be transported to other tissues and organs after uptake by the gastrointestinal tract. Interestingly, although an extremely high dose was administrated, no acute toxicity was observed. In groups exposed to 80 nm and 155 nm particles, histopathological changes were observed in the liver, kidney and in the brain. The biochemical serum parameters also indicated liver, kidney and cardiovascular damage and were higher in mice treated with nano-sized (25 or 80 nm) TiO₂ compared to submicron-sized (155 nm) TiO₂. However, the main weaknesses of this study are the use of extremely high single dose and insufficient characterisation of the particles.

A  2023 study published in the journal Environmental Research, scientists examined the effect of titanium dioxide nanoparticles on important gut bacteria in mice. Their results showed “the growth inhibitory effects could be associated with cell membrane damage caused by titanium dioxide nanoparticles to the bacterial strains. Metabolomics analysis showed that TiO2 NPs caused alterations in multiple metabolic pathways of gut bacteria, such as tryptophan and arginine metabolism, which were demonstrated to play crucial roles in regulating gut and host health.” The researchers also found that four different neuroprotective metabolites “were significantly reduced” in urine and in vitro bacteria and vivo urine samples. The researchers concluded: “Increasing evidence implies that the gut microbiome plays a profound role in regulating host metabolism. Our results illustrated that TiO2 NPs hindered the growth of four beneficial gut bacterial strains.”