MetaboLightsapplication/xmlftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14529/m_MTBLS14529_NMR___v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14529/s_MTBLS14529.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14529/i_Investigation.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14529/a_MTBLS14529_NMR__.txtprimaryOK200ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14529<p>Metabolite annotation was supported using the Human Metabolome Database (HMDB) and reference spectral/compound information from HMDB 5.0.</p>MetaboLightsPublicNuclear Magnetic Resonance (NMR) -Titanium dioxide in food induces sex- and microbiota-dependent metabolic disorders, and worsens high-fat diet outcomes.<p>All 1H-NMR spectra were obtained on a Bruker DRX-600-Avance NMR spectrometer (Bruker) using the AXIOM metabolomics platform (MetaToul) operating at 600.13 MHz using an inverse detection 5-mm 1H-13C-15N cryoprobe attached to a cryoplatform (the preamplifier cooling unit). The 1H-NMR spectra were acquired at 300 K using a one-dimensional cpmgpr1D pulse sequence with water presaturation and a total spin-echo delay (2 ns) of 100 ms. A total of 128 transients were collected into 64,000 data points using a spectral width of 12 pulses/s, a relaxation delay of 2.5 s, and an acquisition time of 2.28 s.</p><p> </p>Sandrine Ellero-SimatosINRAfecesNMR spectroscopy assay<p>80– 100 mg of the cecal content was extracted with 500microl phosphate buffer (0.2 M, pH 7.4) in D2O containing 1% (w/v) of sodium 3-(trimethylsilyl) propionate. After vortexing, each sample was subjected to a freeze-thaw cycle in liquid nitrogen and subsequently homogenized with a tissue lyser (Qiagen, Hilden, Germany) at 20 Hz for 40 s followed by centrifugation at 10,000g for 10 min at 4°C. The supernatants were collected, and the remaining pellet was extracted once more asdescribed above. </p>Mus musculushttps://www.ebi.ac.uk/metabolights/MTBLS14529Sandrine Ellero-Simatos. National Research Institute for Agriculture, Food and Environment. INRAE Toxalim - 180 chemin de Tournefeuille, Toulouse, 31300, France. sandrine.ellero-simatos@inrae.fr.<p>Data were analyzed by applying an exponential window function with a 0.3-Hz line broadening prior to Fourier transformation. The resultant spectra were phased, baseline corrected, and calibrated to trimethylsilylpropanoic acid (TSP) manually using Mnova NMR (version 9.0; Mestrelab Research S.L.). The spectra were subsequently imported into MatLab (R2014a; MathsWorks, Inc.). All data were analyzed using full-resolution spectra. </p>TreatmentDietsandrine.ellero-simatos@inra.fr<p>8 weeks-old female C57BL/6J mice (F0) were purchased from Janvier Labs (Le Genest-Saint-Isle, France) and acclimated to the facilities for 1 week before use. Throughout the study, the mice were maintained in polysulfone cages in a pathogen-free environment maintained at 21 ± 2 °C under a 12-h light–dark cycle. Female mice had ad libitum access to water and food, receiving control or food grade (fg)-TiO2-containing food pellets (=E171). For fg-TiO2-containing diets, the tested compound was added to food pellets to reach 10 mg fg-TiO2/kg bw/d as a target dose of exposure. Mice with a 12h light/dark cycle (21±2°C). After 40 days of treatment, female mice were housed with males and vaginal plug occurrence was monitored to confirm mating and gestation day 0. A group of pups from delivered litters (F1) were then submitted to their F0 respective experimental condition (F1 from F0 control group are unexposed to the food additive) during an overall exposure of 21 weeks (3 weeks from birth to weaning, 2 weeks to reach adult age and 16 weeks of exposure at adulthood). To determine if the dietary pattern could constitute an aggravating factor on the monitored endpoints, a group of F1 mice were subjected to a high fat diet after reaching the adult age (5 weeks) followed by 16 weeks of exposure. Feces were collected on F1 mice after 15 weeks of exposure. </p>MetabolomicsmicrobiotaMetabolomicsMus musculusuntargeted analysisBruker 600 MHz spectrometerglucose intolerance1H nuclear magnetic resonance spectroscopyAXIOMfecesexperimental samplemicrobiotaMetabolomicsMus musculusuntargeted analysisBruker 600 MHz spectrometerglucose intolerance1H nuclear magnetic resonance spectroscopyAXIOMfecesexperimental sample<p>Supernatants obtained from the 2 extractions were combined and centrifuged at 10,000g for 10 min at 4°C. A total of 600microl supernatant was transferred into an NMR tube (outer diameter, 5 mm) pending NMR analysis.</p>TaurineglucosephenylalaninePropionatetaurineaminovalerateLeucineL-glutamateButyratesuccinateacetatecholineTrimethylamineValineglycineuracilalaninetyrosinelactateIsoleucinefalseTitanium dioxide in food induces sex- and microbiota-dependent metabolic disorders, and worsens high-fat diet outcomesUltra-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.2026-05-192026-05-19MTBLS14529HMDB0000039HMDB0000042HMDB0000097HMDB0000123HMDB0000148HMDB0000158HMDB0000159HMDB0000161HMDB0000172HMDB0000190HMDB0000237HMDB0000251HMDB0000254HMDB0000300HMDB0000687HMDB0000883HMDB0000906HMDB0003345HMDB0003355