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BackgroundGenetic variation in the pig genome partially modulates the composition of porcine gut microbial communities. Previous studies have been focused on the association between single nucleotide polymorphisms (SNPs) and the gut microbiota, but little is known about the relationship between structural variants and gut microbial traits.ResultsThe main goal of this study was to assess the effect of porcine genome copy number variants (CNVs) on the diversity and composition of pig gut microbiota. For this purpose, we used whole-genome sequencing data to undertake a comprehensive identification of CNVs followed by a genome-wide association analysis between the estimated CNV status and the gut bacterial diversity in a commercial Duroc pig population. A CNV predicted as gain (DUP) partially harboringABCC2-DNMBP lociwas associated with richness (p-value=5.41×10−5) and Shannon α-diversity (p-value=1.42×10−4). Thein-silicopredicted gain of copies was validated by real-time quantitative PCR (qPCR), and its segregation, and positive association with the richness and Shannon α-diversity of the porcine gut bacterial ecosystem was confirmed in an unrelated F1 (Duroc×Iberian) cross. Furthermore, despite genetic and environmental differences between both populations, the gut microbiota of DUP samples showed a significant over-abundance of theDesulfovibrio, Blautia, Phascolarctobacterium, Faecalibacterium, SuccinivibrioandAnaerovibriogenera.ConclusionsIn summary, this is the first study that evaluate the putative modulatory role of CNVs on pig gut microbiota. Our results advice the relevance of considering the role of host-genome structural variants as modulators of microbial ecosystems, and suggest theABCC2-DNMBPCNV as a host-genetic factor for the modulation of the diversity and composition of the gut microbiota in pigs.