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Crespo-Piazuelo, D.

Publications and source records attributed to Crespo-Piazuelo, D..

5 recordsLinked to original sources

The developing pig respiratory microbiome harbours strains antagonistic to common respiratory pathogens

In the global efforts to combat antimicrobial resistance and reduce antimicrobial use in pig production, there is a continuous search for methods to prevent and/or treat infections. Within this scope, we explored the relationship between the developing piglet nasal microbiome and (zoonotic) bacterial pathogens from birth until ten weeks of life. The nasal microbiome of 54 pigs was longitudinally studied over 16 time-points on nine farms in three European countries (Germany, Ireland, and the Netherlands) using amplicon sequencing targeting the V3-V4 16S rRNA region as well as the tuf gene for its Staphylococcal discrimination power. The piglets age, the farm, and the litter affected the nasal microbiome, with piglets age explaining 19% of the variation in microbial composition between samples. Stabilization of the microbiome occurred around two weeks post-weaning. Notably, while opportunistic pathogens were ubiquitously present, they did not cause disease. The piglet nasal microbiome often carried species associated with gut, skin, or vagina, which suggests that contact with the vaginal and faecal microbiomes shape the piglet nasal microbiome. We identified bacterial Co-Abundance Groups (CAGs) of species that were present in the nasal microbiomes in all three countries over time. Anticorrelation between these species and known bacterial pathogens identified strains that might be exploited for pathogen reduction. Further experimental evidence is required to confirm these findings. Overall, this study advances our understanding of the longitudinal development and factors influencing the piglet nasal microbiome, providing insights into its role in health and disease. ImportanceOur study on longitudinal analysis of the developing nasal microbiota of piglets in farms in three European countries showed consistent microbiome compositions and that colonization of porcine pathogens occurred in relation with anticorrelating species. These findings enhance our knowledge of co-colonizing species in the nasal cavity, and the identified microbial interactions can be explored for the development of interventions to control pathogens in porcine husbandry.

microbiology↗

Integrating large-scale meta-GWAS and PigGTEx resources to decipher the genetic basis of complex traits in pig.

Understanding the molecular and cellular mechanisms that underlie complex traits in pigs is crucial for enhancing their genetic improvement program and unleashing their substantial potentials in human biomedicine research. Here, we conducted a meta-GWAS analysis for 232 complex traits with 28.3 million imputed whole-genome sequence variants in 70,328 individuals from 14 pig breeds. We identified a total of 6,878 genomic regions associated with 139 complex traits. By integrating with the Pig Genotype-Tissue Expression (PigGTEx) resource, we systemically explored the biological context and regulatory circuits through which these trait-associated variants act and finally prioritized 16,664 variant-gene-tissue-trait circuits. For instance, rs344053754 regulates the expression of UGT2B31 in the liver by affecting the activity of regulatory elements and ultimately influences litter weight at weaning. Furthermore, we investigated the conservation of genetic and regulatory mechanisms underlying 136 human traits and 232 pig traits. Overall, our multi-breed meta-GWAS in pigs provides invaluable resources and novel insights for understanding the regulatory and evolutionary mechanisms of complex traits in both pigs and humans.

genetics↗

Construction of a multi-tissue cell atlas reveals cell-type-specific regulation of molecular and complex phenotypes in pigs

The systematic characterization of cellular heterogeneity among tissues and cell-type-specific regulation underlying complex phenotypes remains elusive in pigs. Within the Pig Genotype-Tissue Expression (PigGTEx) project, we present a single-cell transcriptome atlas of adult pigs encompassing 229,268 high-quality nuclei from 19 tissues, annotated to 67 major cell types. Besides cellular heterogeneity within and across tissues, we further characterize prominent tissue-specific features and functions of muscle, epithelial, and immune cells. Through deconvoluting 3,921 bulk RNA-seq samples from 17 matching tissues, we dissect thousands of genetic variants with cell-type interaction effects on gene expression (ieQTL). By colocalizing these ieQTL with variants associated with 268 complex traits, we provide new insights into the cellular mechanisms behind these traits. Moreover, we highlight that orthologous genes with cell-type-specific regulation in pigs exhibit significant heritability enrichment for some human complex phenotypes. Altogether, our work provides a valuable resource and highlights novel insights in cellular regulation of complex traits for accelerating pig precision breeding and human biomedical research.

genetics↗

A compendium of genetic regulatory effects across pig tissues

The Farm animal Genotype-Tissue Expression (FarmGTEx, https://www.farmgtex.org/) project has been established to develop a comprehensive public resource of genetic regulatory variants in domestic animal species, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biology discovery and exploitation in animal breeding and human biomedicine. Here we present results from the pilot phase of PigGTEx (http://piggtex.farmgtex.org/), where we processed 9,530 RNA-sequencing and 1,602 whole-genome sequencing samples from pigs. We build a pig genotype imputation panel, characterize the transcriptional landscape across over 100 tissues, and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We study interactions between genotype and breed/cell type, evaluate tissue specificity of regulatory effects, and elucidate the molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying about 80% of the genetic associations for 207 pig complex phenotypes, and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, corroborating the importance of pigs as a human biomedical model.

genomics↗

Copy number variation on ABCC2-DNMBP loci impacts the diversity and composition of the gut microbiota in pigs

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 harboring ABCC2-DNMBP loci was associated with richness (p-value=5.41x10-5) and Shannon -diversity (p-value=1.42x10-4). The in-silico predicted gain of copies was validated by real-time quantitative PCR (qPCR), and its segregation, and positive association with the richness and Shannon -diversity of the porcine gut bacterial ecosystem was confirmed in an unrelated F1 (DurocxIberian) cross. Furthermore, despite genetic and environmental differences between both populations, the gut microbiota of DUP samples showed a significant over-abundance of the Desulfovibrio, Blautia, Phascolarctobacterium, Faecalibacterium, Succinivibrio and Anaerovibrio genera. 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 the ABCC2-DNMBP CNV as a host-genetic factor for the modulation of the diversity and composition of the gut microbiota in pigs.

microbiology↗