Comparative Effects of Copper Glycinate and Potassium Diformate on Immunity and Gut Microbiota of Pigs—Potential Analysis of Potassium Diformate as a Copper Additive Substitute

Copper supplements are prominent antibiotic alternatives in livestock production, but their excessive use poses environmental risks, necessitating safer substitutes. Potassium diformate (KDF), an organic acid salt, has shown potential as a feed additive, yet its effectiveness in copper-unsupplemented diets remains unclear. This study compared the effects of copper glycinate (Cu_Gly) and KDF on weaned piglets fed a copper-unsupplemented basal diet. Forty-five Meishan piglets were allocated to a control group (basal diet), a Cu_Gly group (basal diet + 60 mg/kg Cu_Gly), or a KDF group (basal diet + 10 g/kg KDF). The KDF group exhibited a lower feed conversion ratio (FCR) than the control group. Although no significant differences in average daily gain were observed, KDF supplementation significantly enhanced immune function by increasing plasma IgG and decreasing IgM, IL-6, and IL-1 levels compared to the control. 16S rRNA sequencing analysis revealed that the Control group was enriched with pathogenic genera (Staphylococcus, Escherichia-Shigella, Brevibacterium) in the ileum and cecum. Cu_Gly supplementation enriched Bacillus, Longispora, and Terrisporobacterin the ileum, while KDF increased the abundance of beneficial taxa (TM7, Nesterenkoniain the ileum; Lachnospiraceae_UCG-007 in the cecum). Correlation analysis showed that the abundances of Escherichia-Shigella and Staphylococcus were negatively correlated with IgG but positively correlated with IgM and IL-6. Cecal Lachnospiraceae_UCG-007 (enriched in the KDF group) was negatively correlated with IL-1. In summary, KDF improved feed efficiency and demonstrates superior immunomodulatory effects compared to Cu_Gly. The enrichment of bacteria linked to metal resistance in the Cu_Gly group suggested a potential drawback not associated with KDF. Therefore, KDF represented a viable and sustainable alternative to copper supplements, offering a combination of improved gut health, enhanced immunity, and a reduced environmental risk profile.