Host genes shape the lower gut microbiota of Holstein cows: evidence from sequence-based GWAS

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Sanchez, Marie-Pierre | Brulin, L. | Cai, Z. | Ducrocq, S. | Even, G. | Martel, S. | Merlin, S. | Audebert, C. | Estellé, J. | Sahana, G. | Croiseau, P.

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International audience. In Holstein cows, our previous works have highlighted the influence of host genetics on the lower gut microbiota, with significant heritability estimates of taxa abundances ranging between 0.05 and 0.22. Additionally, genetic correlations between the lower gut taxa and traits of interest (production, health, fertility) have been observed. In this study, we aim to explore the genetic architecture of the composition of the lower gut microbiota. To this end, samples of 1,875 Holstein cows from 144 French commercial farms were collected and sequenced using 16S rRNA gene sequencing. Cows were genotyped with the 50k SNP array and the genotypes were imputed to the sequence-level using the ninth run of the 1,000 bull genomes project reference panel. The centered-log ratio abundances of 40 heritable genera were then adjusted for non-genetic effects. Genome-Wide Association Studies (GWAS), conducted on approximatively 13 million variants, identified seven Quantitative Trait Loci (-log(p-value)>7.3) and gene-based analyses revealed 37 underlying candidate genes. Notably, Turicibacter abundance was found to be associated with CMC1, an immunity-related gene expressed in the gastrointestinal tract of cattle. We also highlighted a significant association between the abundance of Akkermansia and ABO, a gene known to impact the gut microbiota composition in humans and pigs. To summarize, this study identifies specific regions of the bovine genome that influence the composition of the lower intestinal microbiota, thereby advancing our understanding of the holobiont concept.

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