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Environmental cadmium exposure facilitates mammary tumorigenesis via reprogramming gut microbiota-mediated glutamine metab... 1 1. Introduction 2 2. Materials and methods 2 2.1. Chemicals and reagents 2 2.2. MMTV-Erbb2 mouse models and treatment 2 2.3. Determination of tumorigenesis 3 2.4. Histology, immunofluorescence and immunohistochemical staining 3 2.5. Untargeted metabolomics profiling of mammary tumor specimens 3 2.6. Untargeted metabolomics profiling for fecal samples 3 2.7. Shotgun metagenome sequencing and taxonomic annotation 3 2.8. Identification of glutamine-synthesis microbes 3 2.9. Intestinal permeability assay 5 2.10. Alcian blue and periodic acid-Schiff staining 5 2.11. Transmission electron microscopy 5 2.12. Statistical analysis 5 3. Results 5 3.1. Oral exposure to low-dose Cd enhanced mammary tumorigenesis in MMTV-Erbb2 mice 5 3.2. Low dose Cd exposure promoted intratumoral alanine, aspartate and glutamate metabolism in MMTV-Erbb2 mice 5 3.3. Gln metabolism inhibition repressed Cd-induced mammary tumorigenesis in MMTV-Erbb2 mice 5 3.4. Low dose Cd exposure impaired gut barrier function 8 3.5. Low dose Cd exposure altered gut microbiota-related Gln metabolism in

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nonfiction