Metagenomics of Multiple-Micronutrient-Deficient-Mice

Globally, ~340 million children suffer from multiple micronutrient deficiencies, accompanied by high pathogenic burden and death due to multi-drug resistant bacteria. The microbiome is a reservoir of antimicrobial resistance (AMR), however the implications of undernutrition on the resistome is unclear. Here, we used a postnatal mouse model that is deficient in multiple micronutrients (i.e., zinc, folate, iron, vitamin A, and vitamin B12 deficient) and shotgun metagenomic sequencing of fecal samples to characterize gut microbiome structure and functional potential, and the resistome. Enterobacteriaceae were enriched in micronutrient deficient mice compared to mice fed an isocaloric experimental control diet. The mycobiome and virome was also altered with multiple micronutrient deficiencies including increased fungal pathogens such as Candida dubliniensis and bacteriophages. Despite being antibiotic naïve, micronutrient deficiency was associated with increased enrichment of genes and gene networks encoded by pathogenic bacteria that are directly or indirectly associated with intrinsic antibiotic resistance. This analysis reveals multi-kingdom alterations in the gut microbiome as a result of co-occurring multiple micronutrient deficiencies and the implications for antibiotic resistance.