Foodborne Titanium Dioxide Nanoparticles Induce Stronger Adverse Effects in Obese Mice than Non‐Obese Mice: Gut Microbiota Dysbiosis, Colonic Inflammation, and Proteome Alterations

Abstract The recent ban of titanium dioxide (TiO 2 ) as a food additive (E171) in France intensified the controversy on safety of foodborne‐TiO 2 nanoparticles (NPs). This study determines the biological effects of TiO 2 NPs and TiO 2 (E171) in obese and non‐obese mice. Oral consumption (0.1 wt% in diet for 8 weeks) of TiO 2 (E171, 112 nm) and TiO 2 NPs (33 nm) does not cause severe toxicity in mice, but significantly alters composition of gut microbiota, for example, increased abundance of Firmicutes phylum and decreased abundance of Bacteroidetes phylum and Bifidobacterium and Lactobacillus genera, which are accompanied by decreased cecal levels of short‐chain fatty acids. Both TiO 2 (E171) and TiO 2 NPs increase abundance of pro‐inflammatory immune cells and cytokines in the colonic mucosa, indicating an inflammatory state. Importantly, TiO 2 NPs cause stronger colonic inflammation than TiO 2 (E171), and obese mice are more susceptible to the effects. A microbiota transplant study demonstrates that altered fecal microbiota by TiO 2 NPs directly mediate inflammatory responses in the mouse colon. Furthermore, proteomic analysis shows that TiO 2 NPs cause more alterations in multiple pathways in the liver and colon of obese mice than non‐obese mice. This study provides important information on the health effects of foodborne inorganic nanoparticles.