Copper is an intestinal habitat filter affecting the gut microbiota interactions with Salmonella Typhimurium

Background Foodborne pathogens, including Salmonella enterica serovar Typhimurium ( S . Typhimurium), pose a significant threat to both human health and livestock productivity. The pandemic S. Typhimurium ST34 clone acquired a genomic island (SGI-4) conferring high copper resistance, an adaptation relevant in the context of the widespread use of copper sulphate at therapeutic levels in pig farming. We investigated how high dietary copper influences the piglet gut microbiota and Salmonella -microbiota interactions, that may explain the global spread of S. Typhimurium ST34. Results An on-farm study combined with faecal shotgun metagenomics revealed that several potential Salmonella competitor species, including Bifidobacterium , Escherichia , and Lactobacillus , were less abundant in piglets on high-copper diets. Anaerobic and aerobic culturing alongside whole-genome sequencing of 131 species and copper sulphate susceptibility testing identified copper resistance gene acquisition in selected microbes, particularly within Escherichia . Niche competition assays demonstrated that copper resistance is critical for inter-species competition under high-copper conditions, with Salmonella 's Type VI Secretion System providing a distinct advantage over Escherichia in copper-modified niche. Conclusions Our findings suggest that copper supplementation alters the piglet gut environment, impacting competitive dynamics between pathogenic and commensal bacteria, likely to influence the zoonotic transmission of pathogens.