Effect of Dietary Copper on Intestinal Microbiota and Antimicrobial Resistance Profiles of Escherichia coli in Weaned Piglets Original paper

What was studied?

This original study tested the dietary copper effect on intestinal microbiota in weaned piglets and linked those shifts to Escherichia coli drug resistance. The authors fed piglets a basal diet with or without added copper sulfate at 20, 100, or 200 mg Cu/kg feed and profiled the ileal and cecal microbiota by 16S rDNA sequencing. They also isolated E. coli across time to measure resistance to common antibiotics. The work asked whether a pharmacological copper dose changes gut community makeup and function, increases E. coli abundance, and promotes antimicrobial resistance. The study also checked growth outcomes to see if copper improved gain or feed use while it altered the gut ecosystem.

Who was studied?

The study enrolled healthy weaned piglets (21 ± 1 days old) with similar starting weights. Investigators randomly assigned animals to control or copper-supplemented diets and sampled anal swabs at days 0, 21, and 42 for E. coli isolation. They collected ileal and cecal contents from control and 200 mg Cu/kg groups at weeks 3 and 6 for microbiota and functional predictions. E. coli isolates underwent standard identification and Kirby–Bauer disk diffusion testing against agents that included ampicillin, ceftriaxone, ciprofloxacin, chloramphenicol, and trimethoprim–sulfamethoxazole. The design let the authors compare community structure, inferred metabolic pathways, E. coli abundance, and resistance across dose and time.

Most important findings

Copper did not change alpha diversity but it changed community composition in both ileum and cecum. In the ileum after six weeks, copper shifted Firmicutes and Clostridiaceae and marked the genus Sarcina; in the cecum, copper altered Lactobacillus, Sporolactobacillus, and increased E. coli abundance. Predicted functions showed clear pathway effects. In the ileum, copper lowered pathways tied to energy metabolism, several amino acid routes, butanoate metabolism, nitrogen metabolism, and vitamin and cofactor metabolism. In the cecum, copper raised pathways for branched-chain amino acid biosynthesis and some lipid biosynthesis features and lowered peptidase-related functions.

These shifts point to reduced short-chain fatty acid support in the ileum and a tilt toward protein and lipid pathways in the cecum. Copper exposure increased E. coli richness in the hindgut and raised resistance. In the ileum, resistance to ciprofloxacin rose with copper, while in the cecum, resistance to chloramphenicol rose. Across all sites, most isolates were multidrug resistant, and a larger share of highly resistant strains (≥ six classes) came from copper-fed pigs. By day 42, resistance to ciprofloxacin and chloramphenicol showed a dose-dependent rise, with the 200 mg Cu/kg group highest. Growth metrics did not improve, so the microbiota and resistance costs occurred without clear performance gains. Together, these findings identify a signature of copper-driven shifts that includes higher E. coli abundance and higher rates of fluoroquinolone and phenicol resistance.

Key implications

Clinicians should read high copper intake as a pressure that can favor gut pathobionts and select for resistance. In a microbiome signatures database, this pattern would pair copper exposure with increased E. coli abundance and higher ciprofloxacin and chloramphenicol resistance. The ileal loss of butanoate and energy pathways hints at weakened barrier support, while cecal shifts toward amino acid and lipid routes signal altered nutrient processing. These results support careful copper use in animal production and suggest that copper exposure history in patients with animal contact could inform risk for resistant Enterobacterales. Although this is a swine model, the direction of effect is clear: sustained copper exposure can push gut communities toward E. coli growth and multidrug resistance, with limited host benefit.