As the global population continues to grow exponentially, the competition for resources between livestock and humans has become increasingly intense. Breeding efficient animal breeds, fully utilizing feed resources, and reducing environmental damage are major challenges facing the livestock industry. Thus, we used metagenomics, transcriptomics, and metabolomics to explore how to improve the feed utilization to solve these problems. Our metagenomic analysis revealed a significant up-regulation of Elusimicrobiota at the phylum level within the high residual feed intake (HRFI) group, in comparison to the low residual feed intake (LRFI) group. Additionally, functional analysis using Clusters of Orthologous Groups of proteins (COG) indicated prominent disparities in the category of secondary metabolites biosynthesis, transport, and catabolism between the HRFI and LRFI groups. Furthermore, our metabolomics investigation identified an upregulated expression of the secondary metabolite 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2) in the HRFI group compared to the LRFI group. Liver transcriptome analysis identified prostaglandin-endoperoxide synthase 2 (PTGS2) as a key hub gene, exerting significant regulatory influence within the arachidonic acid pathway. Notably, the metabolite 15d-PGJ2 is a terminal product in the metabolic pathway of arachidonic acid. The correlation analysis between the cecal microbiota and differential metabolites revealed a significant negative correlation between Elusimicrobiota and the metabolite 15d-PGJ2. In summary, we assumed that the intestinal microbiome Elusimicrobiota regulates the expression of the PTGS2 gene, consequently inducing variations in PTGS2 efficiency between the HRFI and LRFI groups, ultimately leading to diverse residual feed intake levels in ducks.