The recent ban of titanium dioxide (TiO₂) as a food additive (E171) in France intensified the controversy on safety of foodborne‐TiO₂ nanoparticles (NPs). This study determines the biological effects of TiO₂ NPs and TiO₂ (E171) in obese and non‐obese mice. Oral consumption (0.1 wt% in diet for 8 weeks) of TiO₂ (E171, 112 nm) and TiO₂ 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 TiO₂ (E171) and TiO₂ NPs increase abundance of pro‐inflammatory immune cells and cytokines in the colonic mucosa, indicating an inflammatory state. Importantly, TiO₂ NPs cause stronger colonic inflammation than TiO₂ (E171), and obese mice are more susceptible to the effects. A microbiota transplant study demonstrates that altered fecal microbiota by TiO₂ NPs directly mediate inflammatory responses in the mouse colon. Furthermore, proteomic analysis shows that TiO₂ 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.