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Background The gut-derived metabolites are key actors in the host-microbiota crosstalk and can have either beneficial or detrimental effects on the host. Gut metabolome could be a potential strategy to enrich the knowledge of host-gut interactions, providing another way of improving key traits such as animal resilience and welfare in livestock systems. Animal resilience has now become a critical livestock trait because of the high demand for more sustainable productions. Environmental variance (VE), the within-individual variance of traits due to environmental factors, is used as a key measure to improve resilience. Studying the gut microbiome composition can reveal the mechanisms behind animal resilience due to its influence on host immunity. The aim of this study was to identify the gut-derived metabolites underlying the VE of litter size (LS), for which we performed an untargeted gut metabolome analysis in two rabbit populations divergently selected for low (n = 14) and high (n = 14) VE of LS. Partial least square-discriminant analysis and Bayesian statistics were computed to determine dissimilarities in the gut metabolites of the rabbit populations. Results We identified 15 metabolites that can discriminate between rabbit populations with a prediction performance of 99.18% for resilient and 90.42% for non-resilient populations. The most reliable metabolites identified were glycerophosphoglycerol, equol, behenoylcarnitine, arachidoylcarnitine, ethyl beta-glucopyranoside, 3-(4-hydroxyphenyl)lactate, N6-acetyllysine, 5-aminovalerate and succinylcarnitine. A great abundance of acylcarnitines and metabolites from the phenylalanine, tyrosine, and tryptophan metabolism were found in the non-resilient population. Acylcarnitines and metabolites from AAAs (like kynurenine and anthranilate) can impact the inflammatory response and the health status of animals. Conclusions This is the first study to identify gut metabolites that can act as the VE of LS biomarkers as well as resilience biomarkers. The smaller number of acylcarnitines and metabolites derived from the phenylalanine, tyrosine and tryptophan metabolism suggested that resilient animals were better able to cope with stressful events. However, further studies will be needed to determine the causal role of these metabolites in health and disease.

BackgroundUnderstanding how the host’s microbiome shapes phenotypes and participates in the host response to selection is fundamental for evolutionists and animal and plant breeders. Currently, selection for resilience is considered a critical step in improving the sustainability of livestock systems. Environmental variance (VE), the within-individual variance of a trait, has been successfully used as a proxy for animal resilience. Selection for reduced VE could effectively shift gut microbiome composition, reshape the inflammatory response, triglyceride and cholesterol levels, and drive animal resilience. This study aimed to determine the gut microbiome composition underlying the VE of litter size (LS), for which we performed a metagenomic analysis in two rabbit populations divergently selected for low (n=36) and high (n=34) VE of LS. Partial least square-discriminant analysis, and alpha- and beta-diversity were computed to determine the differences in gut microbiome composition among the rabbit populations. ResultsWe identified 116 KEGG IDs, 164 COG IDs, and 32 species with differences in abundance between the two rabbit populations studied. These variables achieved a classification performance of the VE rabbit populations of over than 80%. Compared to the high VE population, the low VE (resilient) population was characterised by an underrepresentation of Megasphaera sp., A. muris, B. rodentium, R. bromii, B. togonis and Eggerthella sp., and greater abundances of A. shahii, A. prutedinis, O. splanchnicus, L. fermentum and Sutterella, among others. Differences in abundance were also found in pathways related to biofilm formation, quorum sensing, glutamate, and amino acid aromatic metabolism. All these results suggest differences in gut immunity modulation, closely related to resilience.ConclusionsThis is the first study to show that selection for VE of LS can shift the gut microbiome composition. The results revealed differences in microbiome composition related to gut immunity modulation, which could contribute to the differences in resilience among rabbit populations. The selection-driven shifts in gut microbiome composition should make a substantial contribution to the remarkable genetic response observed in the VE rabbit populations.

espanolEn este trabajo se examinan los resultados obtenidos de la implementacion interuniversitaria del aprendizaje basado en retos (ABR) a traves del uso de las tecnologias de la informacion y comunicacion (TIC) en la asignatura de Mejora Genetica Animal. El reto consistio en llevar a cabo la mejora genetica de un rebano de vacuno lechero, mediante de un software en linea, en un entorno con limitaciones de manejo y economicas reales. Los alumnos obtuvieron una evolucion positiva de los resultados a lo largo del reto, confirmando al ABP como una herramienta util en el aprendizaje de la aplicacion de la mejora genetica animal. Por otra parte, las encuestas realizadas a los alumnos mostraron, en todas las universidades, una alta satisfaccion con este tipo de aprendizaje, aunque indicaron posibles mejoras en la explicacion inicial del reto. La aplicacion de ABR ha sido muy positiva tanto desde un punto de vista de participacion y motivacion de los alumnos, como con el desarrollo del pensamiento critico a traves de la aplicacion practica de conceptos teoricos. EnglishThis paper examines the results obtained from the interuniversity implementation of challenge-based learning (RBL) using information and communication technologies (ICTs) in animal breeding. The challenge faced by students consisted of managing the genetic improvement of a dairy cattle herd in an environment with real management and economic constraints using an online software online. The students achieved a positive evolution of the results along the challenge, confirming the PBA as a useful tool in learning the application of animal breeding. On the other hand, the student surveys showed, in all universities, a high satisfaction with this type of learning, although they indicated possible improvements in the initial explanation of the challenge. The application of ABR has been very positive both from the point of view of student participation and motivation, as well as with the development of critical thinking by the practical application of theoretical concepts.

[EN] This paper presents the results of the first year of the inter-university implementation of challenge-based learning (CBL) in animal breeding. The challenge faced by students from the Universitat Autónoma de Barcelona, the Universidad Politécnica de Madrid and the Universitat Politècnica de València consisted of managing the genetic improvement of a cattle herd in an environment with real management and economic constraints using DCBSP software. The results obtained by the students in the challenge showed an improvement throughout the challenge, which would indicate its usefulness in learning the application of animal breeding. Regarding the students' evaluation of the challenge. The results of the surveys showed high satisfaction with this type of learning in all universities, although they indicated possible improvements in the initial explanation of the challenge. The experience during the first course of pilot application of the CBL has been very positive from the point of view of student participation and motivation, as well as with the development of critical thinking through the practical application of theoretical concepts., [ES] En este trabajo se presentan los resultados del primer año de la implementación interuniversitaria del aprendizaje basado en retos en la asignatura de Mejora Genética Animal. El reto al que se enfrentaron los alumnos de la Universitat Autònoma de Barcelona, la Universidad Politécnica de Madrid y la Universitat Politècnica de València consistió en gestionar la mejora genética de un rebaño de vacuno lechero en un entorno con limitaciones de manejo y económicas reales a través de un software informático DCBS. Los resultados obtenidos por los alumnos en el reto evidenciaron una mejoría a lo largo del mismo, lo que indicaría su utilidad en el aprendizaje de la aplicación de de la mejora genética animal. Respecto a la valoración del reto por parte de los estudiantes, los resultados de las encuestas mostraron una satisfacción elevada con este tipo de aprendizaje en todas las universidades, aunque indicaron posibles mejoras en la explicación incial del reto. La experiencia durante el primer curso de aplicación piloto del ABR ha sido muy positiva tanto desde un punto de vista de participación y motivación de los alumnos, como con el desarrollo del pensamiento crítico a través de la aplicación práctica de conceptos teóricos.

[EN] Background Environmental variance (V-E) is partially under genetic control, which means that the V-E of individuals that share the same environment can differ because they have different genotypes. Previously, a divergent selection experiment for V-E of litter size (LS) during 13 generations in rabbit yielded a successful response and revealed differences in resilience between the divergent lines. The aim of the current study was to identify signatures of selection in these divergent lines to better understand the molecular mechanisms and pathways that control V-E of LS and animal resilience. Three methods (F-ST, ROH and varLD) were used to identify signatures of selection in a set of 473 genotypes from these rabbit lines (377) and a base population (96). A whole-genome sequencing (WGS) analysis was performed on 54 animals to detect genes with functional mutations. Results By combining signatures of selection and WGS data, we detected 373 genes with functional mutations in their transcription units, among which 111 had functions related to the immune system, stress response, reproduction and embryo development, and/or carbohydrate and lipid metabolism. The genes TTC23L, FBXL20, GHDC, ENSOCUG00000031631, SLC18A1, CD300LG, MC2R, and ENSOCUG00000006264 were particularly relevant, since each one carried a functional mutation that was fixed in one of the rabbit lines and absent in the other line. In the 3MODIFIER LETTER PRIMEUTR region of the MC2R and ENSOCUG00000006264 genes, we detected a novel insertion/deletion (INDEL) variant. Conclusions Our findings provide further evidence in favour of V-E as a measure of animal resilience. Signatures of selection were identified for V-E of LS in genes that have a functional mutation in their transcription units and are mostly implicated in the immune response and stress response pathways. However, the real implications of these genes for V-E and animal resilience will need to be assessed through functional analyses., We are grateful to CEGEN-PRB3-ISCIII for their genotyping service, supported by Grant No PT17/0019 of the PE I+D+i 2013-2016, funded by ISCIII and ERDF. Cristina Casto-Rebollo acknowledges a FPU17/01196 scholarship from the Spanish Ministry of Science, Innovation and Universities. This study was supported by Projects AGL2014-5592, C2-1-P and C2-2-P, and AGL2017-86083, C2-1-P and C2-2-P, funded by the Spanish Ministerio de Ciencia e Innovacion (MIC)-Agencia Estatal de Investigacion (AEI) and the European Regional Development Fund (FEDER).

[EN] Background Environmental variance (V-E) is partly under genetic control and has recently been proposed as a measure of resilience. Unravelling the genetic background of the V-E of complex traits could help to improve resilience of livestock and stabilize their production across farming systems. The objective of this study was to identify genes and functional mutations associated with variation in V-E of litter size (LS) in rabbits. To achieve this, we combined the results of a genome-wide association study (GWAS) and a whole-genome sequencing (WGS) analysis using data from two divergently selected rabbit lines for high and low V-E of LS. These lines differ in terms of biomarkers of immune response and mortality. Moreover, rabbits with a lower V-E of LS were found to be more resilient to infections than animals with a higher V-E of LS. Results By using two GWAS approaches (single-marker regression and Bayesian multiple-marker regression), we identified four genomic regions associated with V-E of LS, on chromosomes 3, 7, 10, and 14. We detected 38 genes in the associated genomic regions and, using WGS, we identified 129 variants in the splicing, UTR, and coding (missense and frameshift effects) regions of 16 of these 38 genes. These genes were related to the immune system, the development of sensory structures, and stress responses. All of these variants (except one) segregated in one of the rabbit lines and were absent (n = 91) or fixed in the other one (n = 37). The fixed variants were in the HDAC9, ITGB8, MIS18A, ENSOCUG00000021276 and URB1 genes. We also identified a 1-bp deletion in the 3 ' UTR region of the HUNK gene that was fixed in the low V-E line and absent in the high V-E line. Conclusions This is the first study that combines GWAS and WGS analyses to study the genetic basis of V-E. The new candidate genes and functional mutations identified in this study suggest that the V-E of LS is under the control of functions related to the immune system, stress response, and the nervous system. These findings could also explain differences in resilience between rabbits with homogeneous and heterogeneous V-E of litter size., This study was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) with the Projects AGL2014-55921, C2-1-P and C2-2-P, and AGL2017-86083, C2-1-P and C2-2-P and the Grant RYC-2016-19764.

[EN] An experiment of divergent selection for intramuscular fat was carried out at Universitat Politecnica de Valencia. The high response of selection in intramuscular fat content, after nine generations of selection, and a multidimensional scaling analysis showed a high degree of genomic differentiation between the two divergent populations. Therefore, local genomic differences could link genomic regions, encompassing selective sweeps, to the trait used as selection criterion. In this sense, the aim of this study was to identify genomic regions related to intramuscular fat through three methods for detection of selection signatures and to generate a list of candidate genes. The methods implemented in this study were Wright's fixation index, cross population composite likelihood ratio and cross population - extended haplotype homozygosity. Genomic data came from the 9th generation of the two populations divergently selected, 237 from Low line and 240 from High line. A high single nucleotide polymorphism (SNP) density array, Affymetrix Axiom OrcunSNP Array (around 200k SNPs), was used for genotyping samples. Several genomic regions distributed along rabbit chromosomes (OCU) were identified as signatures of selection (SNPs having a value above cut-off of 1%) within each method. In contrast, 8 genomic regions, harbouring 80 SNPs (OCU1, OCU3, OCU6, OCU7, OCU16 and OCU17), were identified by at least 2 methods and none by the 3 methods. In general, our results suggest that intramuscular fat selection influenced multiple genomic regions which can be a consequence of either only selection effect or the combined effect of selection and genetic drift. In addition, 73 genes were retrieved from the 8 selection signatures. After functional and enrichment analyses, the main genes into the selection signatures linked to energy, fatty acids, carbohydrates and lipid metabolic processes wereACER2, PLIN2, DENND4C, RPS6, RRAGA(OCU1),ST8SIA6, VIM(OCU16),RORA, GANCandPLA2G4B(OCU17). This genomic scan is the first study using rabbits from a divergent selection experiment. Our results pointed out a large polygenic component of the intramuscular fat content. Besides, promising positional candidate genes would be analysed in further studies in order to bear out their contributions to this trait and their feasible implications for rabbit breeding programmes., The authors thank Federico Pardo, Veronica Juste and Marina Morini for technical assistance. The work was funded by project AGL2014-55921-C2-1-P and AGL2017-86083-C2-P1 from National Programme for Fostering Excellence in Scientific and Technical Research - Project I+D. B. Samuel Sosa-Madrid was supported by a FPI grant from the Economy Ministry of Spain (BES-2015-074194).