HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
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50 échantillons, 5 minutes et 40 secondes. Bref : c'est le temps que j'ai passé à retraiter mes datas avec MzMine4 !
International audienc
Plasma cytokine and chemokine levels during natural outbreaks of bovine respiratory disease in young bulls on feedlots
International audienceBovine Respiratory Disease (BRD) is a leading cause of morbidity and mortality in young cattle upon feedlot arrival. The immune response plays a dual role in infection control and lung tissue damage, but few studies have assessed cytokine levels during natural BRD outbreaks. Advances in multiplexed assays now allow for broader cytokine and chemokine profiling in cattle. In this nested case–control study, 184 young bulls from nine French fattening farms were clinically assessed and underwent thoracic ultrasonography (TUS) weekly during the first month on feed. BRD cases ( n = 98) and matched healthy controls ( n = 86) were selected based on clinical signs. Fifteen cytokines and chemokines were quantified in plasma using a bovine-specific bead-based multiplex assay, on the day an animal was first detected as sick and in its matched control sampled on the same day. BRD-associated pathogens were assessed using qPCR on nasal swabs and paired serology. The link between cytokines and clinical, microbiological, and preconditioning (vaccination and preventive antibiotic treatment) variables was investigated using the Wilcoxon-Mann–Whitney test, mixed-effects linear regression models, and multivariate clustering. Cytokine and chemokine levels did not distinguish clinically sick from healthy animals. No specific cytokine profile was associated with infection by a given pathogen. However, IL-17A and IFN- γ concentrations were positively associated with treatment relapse and disease severity, suggesting that they may have prognostic potential. Cluster analysis revealed three subgroups with distinct cytokine patterns and health outcomes, in association with preconditioning variables, highlighting the critical role of these interventions in shaping the immune response during BRD outbreaks. This study is the first to report the measurement of such a wide range of cytokines during spontaneous BRD episodes in young bulls. While not diagnostic when considered individually, cytokine profiles may hold prognostic value and could be integrated into multimodal risk stratification tools, in combination with clinical, microbiological data, and TUS results, to improve BRD management in the field. Preconditioning practices, such as vaccination or preventive antibiotic administration, significantly influence early immune responses and should further be investigated to refine prevention strategies and individualize health monitoring protocols at feedlot entry
Liens entre signes cliniques, lésions anatomo-pathologiques et anomalies échographiques pulmonaires chez les bovins de moins de 2 ans : étude à partir d’une série de 42 cas
Infectious bronchopneumonia is the second most common disease in young cattle. As clinical diagnosis is often difficult, thoracic ultrasound is a complementary exam to consider. A great deal of work has been done on dairy calves, but there are very few studies on other breeds. Our study aims to determine whether the data collected on dairy calves can be extended to other bovine breeds. A clinical examination, lung ultrasound and lung necropsy were carried out on 42 cattle less than two years of age. Sensitivity (Se = 71%) and specificity (Sp = 79%) values for thoracic ultrasound in the diagnosis of bronchopneumonia were established from this subset of cases. Thoracic ultrasound is an effective method for detecting BPI in cattle under two years of age, though it has a lower sensitivity than that established in dairy calves.Les bronchopneumonies infectieuses sont la deuxième affection la plus fréquente des jeunes bovins. Le diagnostic clinique étant souvent difficile, l’échographie est un examen complémentaire de choix. De nombreux travaux ont été réalisés sur des veaux laitiers, mais il existe très peu d’études dans les autres races. L’objectif de notre étude est de déterminer si les données recueillies sur les veaux laitiers peuvent être étendues à l’ensemble des races bovines. Un examen clinique, une échographie pulmonaire ainsi qu’un examen nécropsique des poumons ont été réalisés sur 42 bovins de moins de deux ans. Des valeurs de sensibilité (Se = 71%) et de spécificité (Sp = 79%) de l’échographie pulmonaire pour le diagnostic d’une broncho-pneumonie ont été établies à partir de cet échantillon de cas. L’échographie est un examen complémentaire d’intérêt pour détecter les BPI chez les bovins de moins de deux ans malgré une sensibilité moindre que celle établie chez les veaux laitiers
Transgenerational transmission of an environmental modification in quails: changes in phenotypic variance components across three generations
While epigenetic variations can contribute to shaping phenotypic diversity, it can be challenging to isolate and quantify the portion of trait variability under epigenetic influence. The present study compares the phenotypic response for different phenotypes of two epilines of Japanese quails ( Coturnix japonica ), with similar genetic structure across three generations following an initial genistein ingestion in the ancestors’ diet. Linear and linear mixed models were fitted to extract the fraction of variance allocated to multiple factors such as dam, family, sex, reproductive status and epiline. The latter was found to be significantly associated with body weight and with heart, abdominal fat and testicle weight adjusted by body weight. The proportion of phenotypic variance explained by the epiline progressively increased from the first generation (G0) to the last (G2), leading - for example in body weight at slaughter - to an average difference for adult males and females in G2 of 9 grams and 14 grams respectively, between genistein treated offspring (epi+) and controls (epi-). These findings suggest a possible transgenerational effect of the initial diet disruption. In tissue weights, production and behavioural traits, the effect of the epiline accounted for smaller fractions of phenotypic variability and overall large residual variances were observed, underlining the complex nature of the analysed traits. This innovative experimental design allowed for a characterization of the impact of transgenerational effects on a variety of phenotypic traits, which will be useful for prioritizing traits for future genetic and epigenetic association studies. Implications Nowadays, changes in the environment occur more frequently and livestock species can struggle to adapt to these rapid shifts. It is therefore important to understand the impact of the environment on animals. In this study, we evaluate how an initial modification in prior generations can also affect subsequent ones. By collecting different traits of interest (growth, tissues, production, and behaviour), we compare the response to a change in the ancestors diet across three successive generations. Our findings highlight the importance of considering the potential multi-generational effects of changes to the environment. This could provide guidelines for better poultry management in order to ensure animal welfare while maintaining sustainable production yields
Pilotage du microbiote intestinal pour améliorer les performances des animaux d’élevage
Dans ce document d’HDR, je présente les principaux projets auxquels j'ai participé ou que j'ai dirigés, l’encadrement de deux postdoctorants et de deux étudiants en thèse à 50%, ainsi que la cohérence des questions de recherche abordées au fil de ma carrière. Je détaillerai davantage les résultats dans la partie 3, dans laquelle je mettrai en lumière l’équilibre entre les développements méthodologiques, la science fondamentale et la science appliquée. J’exposerai également mon projet pour les 5 années à venir.En novembre 2011, j’ai rejoint l’INRAE pour travailler sur le microbiote intestinal du lapin et du porc. J’ai rapidement orienté mes travaux vers l’étude de l’interaction hôte-microbiote, en initiant une collaboration avec des généticiens et des experts des gaz fermentaires. Le projet DISEFAL a révélé que les lapins dits efficaces en termes de digestion sont plus riches en certaines bactéries productrices de propionate, un acide gras à chaîne courte bénéfique pour la santé intestinale.Je me suis ensuite lancé dans l’étude des liens entre microbiote et performances zootechniques dans le cadre du projet MicroRabbits, financé par le département PHASE. Ce projet a permis de démontrer que la sélection génétique des lapins n’avait pas favorisé un microbiote optimal pour l'efficacité alimentaire, et que l’adoption d’un microbiote sain chez les animaux non-efficaces conduisait à des gains de performance.Parallèlement, je me suis investi dans plusieurs projets visant à comprendre et moduler le microbiote, comme MicroRESET, qui a exploré l’utilisation de la transplantation fécale pour lutter contre l’antibiorésistance en élevage. Ce projet a permis de développer des outils et des méthodologies innovants pour analyser les microbiotes de porcs et de lapins et d’identifier des consortia sans gènes d’antibiorésistance.À travers des collaborations avec des chercheurs experts de différents domaines, des vétérinaires et des partenaires industriels, j’ai mené à bien plusieurs projets, notamment une thèse, dans lesquelle j’ai étudié l’impact des microbiotes sur la robustesse des animaux, en lien avec leur génétique et leur nutrition.En parallèle, j’ai exploré de nouvelles technologies pour cultiver et analyser des communautés microbiennes, telle que la culture en microfluidique. Ces expériences ont permis de réactualiser d’anciennes techniques en les adaptant pour qu’elles soient haut-débit dans le but de mieux comprendre et manipuler les microbiotes des animaux d'élevage.Dans l’ensemble, mes projets reflètent une démarche intégrée, combinant approche fondamentale et appliquée, et visant à développer des solutions innovantes pour améliorer la santé et la productivité des animaux d’élevage
Caractérisation d’un nouvel acide biliaire secondaire impliqué dans la douleur viscérale liée au syndrome de l’intestin irritable
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by chronic abdominal pain and bowel habit disturbances, which significantly impact patients' quality of life. Despite a global prevalence estimated between 5% and 10%, diagnosis and management remain limited due to the lack of biomarkers and an incomplete understanding of its pathophysiology. This thesis focuses on bacterial metabolites from the gut microbiota in patients with IBS. The first part involves the quantification of bacterial lipid metabolites. The second analyzes the potential role of a newly identified secondary bile acid, 3βCA, which is significantly increased in IBS patients. 3βCA correlates with clinical pain, induces visceral hypersensitivity in mice, and activates TGR5/TRPA1 on sensory neurons. These findings offer new insights into the pathophysiology of IBS and may help identify future biomarkers.Le syndrome de l’intestin irritable (SII) est un trouble fonctionnel intestinal caractérisé par des douleurs abdominales chroniques et troubles du transit, qui affecte la qualité de vie des patients. Malgré une prévalence mondiale estimée entre 5 et 10 %, son diagnostic et sa prise en charge restent limités par l’absence de biomarqueurs et une compréhension physiopathologique incomplète. Cette thèse s’intéresse aux métabolites bactériens du microbiote intestinal chez les patients atteints de SII. La première partie concerne la quantification des métabolites lipidiques bactériens. La seconde analyse le rôle potentiel d’un métabolite, le 3βCA, un acide biliaire secondaire nouvellement identifié, significativement augmenté chez les patients atteints de SII. Le 3βCA corrèle avec la douleur clinique, induit une hypersensibilité viscérale chez la souris, et active TGR5/TRPA1 sur les neurones sensoriels. Ces résultats ouvrent des perspectives pour mieux comprendre la physiopathologie du SII et identifier de futurs biomarqueurs
Empowering Bioinformatics Communities with nf-core: The success of an open-source bioinformatics ecosystem
International audienc
Efficient pigs do not always have less environmental impacts: insights from an individual-based model to assess environmental, economic and technical performances
International audiencePig production is facing economic and environmental challenges. In previous studies, the environmental impacts of pig farming have mainly been assessed with group-feeding strategies. A feeding strategy applied to a group of pigs results in unequal animal responses and environmental impacts due to inter-individual variability in lean growth potential and nutritional requirements. The present work aimed at fairly evaluating pigs’ responses in a given production system. We designed a methodological approach able to (i) virtually assess technical, economic and environmental performances of each fattened pig within a population; and (ii) help determine the pig characteristics resulting in contrasted environmental performances in a conventional system including feedstuffs classically used on French commercial farms. For that purpose, experimental data collected on 732 entire Large White males were used to adjust growth profiles using InraPorc® software and to estimate amino acid (AA) requirements of pigs. Each individual profile was used to generate a virtual population of 1 000 pigs. For each population, technical performances were simulated with an individual-based model, economic and environmental evaluations were applied to these performances, and then averaged to assess the individual performance of each of the 732 original pigs. Climate change, use of fossil resources, acidification, eutrophication potentials and land use impacts were evaluated per kg live body weight at farm gate through life cycle assessment. A principal component analysis was applied to the correlation matrix between environmental and economic performances to identify their main drivers. Hierarchical clustering was used to group pigs with similar responses. Three clusters of pigs were distinguished. Cluster 1, with best environmental and economic performances, combined low feed conversion ratios, relatively low-impact feeds and high protein deposition potential (PDm). Clusters 2 and 3 displayed worst environmental performances. Cluster 3 had similar feed efficiency and economic performances as Cluster 1, but higher initial AA requirements, resulting in high-impact feeds and a lower protein deposition. Cluster 2 had the lowest-impact feeds due to the lowest initial AA requirements, and were the least efficient. Feed efficiency, PDm and AA requirements of pigs at the beginning of fattening were the main factors affecting environmental performances. Contrary to previous studies where group feeding was modelled, we show that feed efficiency alone cannot be retained to identify pigs with the lowest impacts. Other pig characteristics such as AA requirements, PDm and environmental impacts should be accounted for to lower the environmental impacts of pig production
Triggering tumorigenic signaling: Succinate dehydrogenase inhibitor (SDHi) fungicides induce oncometabolite accumulation and metabolic shift in human colon cells
International audienceSuccinate dehydrogenase inhibitors (SDHi) are fungicides used worldwide to control the proliferation of fungi in crops. They act by blocking the activity of succinate dehydrogenase (SDH), a universal enzyme involved in mitochondrial functions and metabolism. While SDH-encoding genes are tumour suppressors, which loss-of-function mutations predispose to different types of rare tumors in humans, the consequences of chemical inactivation of SDH by SDHi remain largely unknown, particularly regarding their carcinogenic potential. Here, we investigated the metabolic and cellular impact of SDHi on human non-cancer and transformed colon cells. We show that SDHi inhibit SDH activity and increase the level of succinate, known to act as an oncometabolite in SDH-deficient cancers. SDHi exposure also induces a Warburg-like metabolic reprogramming typical of cancer cells, associated with transcriptomic and morphological changes promoting cell migration and invasion. These effects are enhanced in transformed colon cells carrying mutations in colorectal cancer (CRC) driver genes. These findings provide the first evidence that SDHi-mediated chemical inactivation of SDH mimics some metabolic and phenotypic features previously described in human tumors with SDH genetic deficiencies. Given that loss of SDH expression in CRC patients correlates with a poor prognosis, these patients could represent a population sensitive to SDHi exposure. Therefore, it would be wise to include them in biomonitoring programs. Finally, our work highlights the need to improve regulatory assessment procedures to take better account of SDHi mode of action, by developing relevant tests to cover the multiple key events linked to SDH inactivation and assess the resulting mitochondrial toxicity
Détection de QTL de résistance à la Pasteurellose
International audiencePasteurellosis is the first cause of female mortality in rabbit farms. During the RELAPA project, 964 rabbits were inoculated at 6 weeks of age with a pyogenic strain of Pasteurella multocida and their response to the infection was monitored during 14 days. Various pasteurellosis resistance traits were registered. Among those rabbits, 921 were genotyped with the rabbit chip containing almost 200 000 SNP (single nucleotide polymorphism) markers. After quality control, 82,353 to 107,539 SNP (depending on the rabbit line) and 919 rabbits (from 137 to 175 rabbits per line) were retained for association analyses. The GWAS were performed using the GEMMA software, applying a mixed animal model with a linear regression on each SNP. In total, 93 SNP detected on 9 chromosomes and in 5 rabbit lines were associated with pasteurellosis resistance or pre-weaning growth.La pasteurellose est la première cause de mortalité des femelles en élevage cunicole. Lors du projet RELAPA, 964 lapins de 6 lignées ont été inoculés à l'âge de 6 semaines avec une souche pyogène de Pasteurella multocida et leur réponse à l'infection a été suivie pendant 14 jours. Différents caractères de résistance à la pasteurellose ont été enregistrés. Parmi ces lapins, 921 ont été génotypés avec la puce lapin contenant près de 200 000 marqueurs SNP (single nucleotide polymorphism). Après contrôle qualité, de 82 353 à 107 539 SNP ont été conservés suivant les lignées, et 919 lapins (de 137 à 175 lapins par lignées) ont été retenus pour les études d'association pangénomique. Le logiciel GEMMA a été utilisé, en appliquant un modèle mixte animal utilisant une régression linéaire pour chaque SNP. Au total, 93 SNP, répartis sur 9 chromosomes et dans 5 lignées, sont associés à des caractères de résistance à la pasteurellose ou de croissance pré-sevrage