Astragalus polysaccharides reshape gut resistome of postpartum dairy cows.

Antibiotic resistance genes (ARGs) in livestock feces represent an important environmental reservoir of antimicrobial resistance. Natural product intervention is a potential strategy for regulating the gut microbiome of livestock; however, its effects on the gut resistome of postpartum dairy cows remain poorly understood. In this study, we investigated the effects of Astragalus polysaccharides (APS) supplementation on the fecal microbiome, ARGs, mobile genetic elements (MGEs), virulence factors (VFs), and ARG-carrying metagenome-assembled genomes (MAGs) in dairy cows during postpartum period. Alpha and beta diversity analyses showed that APS supplementation did not significantly alter the global resistome, mobilome, or virulome structure. The content of several ARGs and VFs, including AAC(6')-Iw, qacEdelta1, ast, PM_RS00425, and sdrF, significantly decreased in the APS group, and several plasmid-associated MGEs genes showed group-specific changes. Co-occurrence network analysis revealed complex associations between ARGs, VFs, and core bacterial taxa, with Paludibacter and Parabacteroides identified as potential microbial reservoirs of resistance- and virulence-associated genes. Furthermore, 101 metagenome-assembled genomes (MAGs) were recovered, 42 of which carried multiple ARGs. Bin.1, assigned to Scatovivens, had the highest ARG count. APS supplementation reduced the overall ARG load, particularly the ARG contribution in bin.1. However, APS utilization potential was not significantly correlated with ARG density or ARG load across MAGs. Thus, this study provides new insights into APS supplementation and nutritional strategies that can mitigate the fecal ARG burden in dairy production.