Titanium dioxide in food induces sex- and microbiota-dependent metabolic disorders, and worsens high-fat diet outcomes

ABSTRACT: Ultra-processed food consumption has been linked to the rising global burden of metabolic diseases, but the specific contribution of additives commonly used in these products remains unclear. Given the bactericidal properties of the food-grade (fg) additive titanium dioxide (TiO2) and the key role of the gut microbiota in maintaining metabolic health, this study aimed to determine whether daily exposure to this widely used additive induces intestinal dysbiosis promoting metabolic disorders. MiniBioReactor Arrays inoculated with fecal microbiota from healthy donors were exposed to fg-TiO2. Fecal samples from normo-weight or obese children were analyzed for titanium content and microbiota-derived markers. Mice were exposed to fg-TiO2 at human dietary doses from gestation to adulthood under standard or high-fat diet (HFD), assessing metabolic outcomes and microbiota-mediated effects through fecal microbiota transfer (FMT) to germ-free mice. Fg-TiO2 reshaped human microbiota structure in vitro, consistently affecting taxa linked to immune signaling. Obese children had higher fecal titanium levels than normo-weight peers, correlating with fecal flagellin levels, suggesting a dysbiotic profile. Lifelong exposure to fg-TiO2 induced sex-dependent dysbiosis with glucose metabolism impairment in male mice, characterized by increased fasting insulin, HOMA-IR, and pro-inflammatory fecal markers. FMT demonstrated that an fg-TiO2-altered microbiota was sufficient to transfer glucose intolerance. Under HFD, fg-TiO2 exacerbated hepatic, metabolic and gut barrier disturbances. Our findings identified fg-TiO2 as an environmental factor disrupting gut microbiota and promoting sex-dependent metabolic dysfunction, exacerbating HFD metabolic outcomes. These results warrant further epidemiological investigations on food additive exposure and metabolic health.

INSTRUMENT(S): Nuclear Magnetic Resonance (NMR) -

PROVIDER: MTBLS14529 | MetaboLights | 2026-05-19

REPOSITORIES: MetaboLights