HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
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Bacterial nanoparticles as a potent and safe alternative to BCG for bladder cancer immunotherapy
No full textInternational audienceBladder cancer is the second most common malignancy of the urogenital system, with non-muscle-invasive forms being the most prevalent. While therapy with intravesical instillation of Bacillus Calmette-Gu & eacute;rin (BCG) is widely used, it shows variable efficacy and notable side effects, which prompts the need for new treatments. This study introduces a nanoscale biotherapy against bladder cancer using bacterial extracellular vesicles (bEVs) from Escherichia coli. In an orthotopic syngeneic rat model of bladder cancer with luciferase-tagged tumour cells, intravesical bEVs treatment significantly inhibited tumour growth compared to the gold standard therapy: BCG. Indeed, compared to BCG, bEVs treatment led to superior tumour regression, with 60% of treated animals showing complete tumour clearance versus 20% in the BCG-treated group. Moreover, we observed strong local immune activation, namely T cell infiltration and mucosal lymphoid aggregates, which negatively correlated with tumour size, suggesting that bEVs efficacy is due, at least in part, to their ability to induce a strong antitumor immune response. Notably, bEVs caused no mortality or systemic toxicity. Altogether, the present study constitutes a striking illustration of translational medicine, where the properties of a bacterial compound can be harnessed for patient benefit
Estimation of genetic parameters for fertility and prolificacy in the Lacaune meat sheep population carrying a hyperprolific gene
No full textInternational audienceFrom an economic perspective, meat sheep farms depend on several components, such as reproductive traits, which can be influenced by numerous factors of variation. In this study, the effects of two kinds of oestrus, a) induced oestrus (IO) and b) the first natural return oestrus (FRO), and of the genotype encoding a hyperprolific gene (FecL) on prolificacy and fertility were tested. The genetic parameters of these two traits were also estimated using BLUP animal models with ASReml software. The data related to 68,652 matings were recorded from 2010 to 2020 for 20,770 ewes from the Lacaune Ovi-Test population. The oestrus type, which is associated with the use of hormonal treatment, improved the two reproductive traits studied. As expected, one copy of the mutated allele of the FecL gene had an effect on the prolificacy of + 0.5 lambs per lambing but had no effect on fertility. Moreover, the animal variances estimated during this study for prolificacy and fertility after IO and on FRO were low but still explained a share of the phenotype variance of +/- 0.5 lambs per litter and +/- 0.20 fertility points around the average. The repeatabilities and heritabilities of prolificacy and fertility were low but consistent with the literature. Owing to the structural relationship between the oestrus type in our dataset, less data were available on FRO, making its genetic evaluation less accurate than the genetic evaluation on IO
Danger et risque en toxicologie alimentaire : l’exemple de l’acétamipride
No full textFiche Question sur... de l'Encyclopédie de l'Académie d'agriculture de France.Fiche consultable sur le site internet www.academie-agriculture.fr onglet "Publications" puis "Table des matières des documents de l'Encyclopédie"Reproduction autorisée sous réserve d'en citer la provenance Encyclopédie : Question surIt is essential to clearly distinguish between the concepts of hazard and risk in toxicology, regardless of the substance being studied.In the case of acetamiprid, there is a safety margin of approximately 200,000 between the potentially carcinogenic dose identified by EFSA in 2016 in animals, the hazard, and actual exposure based on the ADI.Neither the International Agency for Research on Cancer nor the European Chemicals Agency have classified acetamiprid as a carcinogen to date (as of 2025).Il est essentiel de bien discriminer les notions de danger et de risque en toxicologie, quelle que soit la substance étudiée. Dans le cas de l’acétamipride, il y a une marge de sécurité d’environ 200 000 entre la dose potentiellement cancérigène identifiée par l’Efsa en 2016 chez l’animal, le danger et l’exposition réelle au vu de la DJA. Ni le Centre international de recherche contre le cancer, ni l’Agence européenne des produits chimiques n’ont classé à ce jour (en 2025) l’acétamipride parmi les produits cancérigènes
Inherited non‐syndromic polydactyly in a Berber and Arabian‐Berber horse family
No full textInternational audienceBackground: Supernumerary digits, or polydactyly, have been described in various species including humans, wild and domestic animals. In horses, it represents the most common congenital limb malformation, which has only been described in isolated cases or nuclear families. Molecular aetiology has not been reported.Objectives: To characterise the phenotype of a non‐syndromic pre‐axial polydactyly in a horse family and to decipher the inheritance pattern.Study design: Retrospective study.Methods: Forty‐three members of the family including a previously reported polydactyl case were recruited. Available clinical and radiographical findings from the initial case and its family members were summarised and karyotypic examinations of the horses were performed.Results: On clinical examination, eight horses (including the previously reported case) had one or two supernumerary digits on their forelimbs and one additional case was diagnosed using radiography. Additional digits were located on the medial side of the forelimbs in all nine polydactyl horses. Radiography highlighted variable expression of the defect, which was either unilateral or bilateral. Variations were observed in the number of supernumerary phalanges, the level of development of a rudimentary metacarpal bone, the individualisation of a supernumerary digit and the existence of a rudimentary hoof. All nine affected horses were related to a single stallion. Pedigree analysis revealed that the most likely inheritance pattern was autosomal dominant with incomplete penetrance and variable expressivity. A more complex mode could not be ruled out. Main limitations Restricted recruitment of the family members due to confidentiality constraints and to international dispersal of the relatives, quality of radiographs.Conclusions: We describe an equine preaxial polydactyly in a Berber and Arabian‐Berber family most likely with autosomal dominant inheritance with incomplete penetrance. This is the first description of an inherited non‐syndromic polydactyly in horses.Contexte: Des doigts surnuméraires, ou polydactylie, ont été décrit chez plusieurs espèces incluant l'homme, de même que les animaux domestiques et sauvages. Chez le cheval, il s'agit de la malformation congénitale des membres la plus fréquente, ayant été décrite dans des cas isolés seulement ou au sein de familles nucléaires. Une étiologie moléculaire n'a pas encore été rapportée.Objectifs: Caractériser le phénotype d'une polydactylie non syndromique de type préaxial au sein d'une famille équine et identifier un mode de transmission.Type d'étude: Étude rétrospective.Méthodes: À partir d'un étalon Barbe polydactyle présenté à l'École Vétérinaire d'Alfort (France), 43 chevaux (8 polydactyles, 35 non‐polydactyles) de sa famille ont été recruté. Des examens cliniques, radiographiques et karyotypiques de certains chevaux de cette famille ont été faits.Résultats: Une famille équine Barde et Arabe croisé Barbe avec polydactylie préaxiale non syndromique a été identifiée. À l'examen clinique, huit chevaux ont montré un ou deux doigts surnuméraires au niveau des membres thoraciques et une jument a été diagnostiquée par radiographie. Les doigts additionnels étaient localisés du côté médial des membres thoraciques chez les 9 chevaux polydactyles. L'analyse radiographique a identifié une expression variable de ce défaut, soit unilatéral ou bilatéral. Des variations ont été observées quant au nombre de phalanges surnuméraires, pour le développement des os métacarpiens, pour l'individualisation d'un doigt surnuméraires et l'existence d'un sabot rudimentaire. L'ensemble des neuf chevaux étaient reliés au même étalon. L'analyse généalogique a révélé que le mode de transmission le plus probable était autosomique dominant avec une pénétrance incomplète et une expressivité variable. Une mode de transmission plus complexe ne peut être exclu. Limites Principales Recrutement restreint des membres de la famille due à des contraintes de confidentialité et des membres de la famille situés dans d'autres pays; qualité des radiographies.Conclusion: Nous avons découvert une polydactylie équine préaxiale chez une famille Barbe et Arabe croisé Barbe ayant le plus probablement un mode de transmission autosomique dominant avec pénétrance incomplète. À ce que nous sachions, ceci représente la toute première description de polydactylie non syndromique héréditaire chez le cheval
Comprehensive genomic analysis of antibiotic resistance plasmids in animal-associated Staphylococcus aureus in France
No full textInternational audienceIn Staphylococcus aureus , an animal pathogen and zoonotic agent, plasmids play a pivotal role in the acquisition and spread of antibiotic resistance genes (ARGs). This study investigated the plasmid content of 329 S . aureus isolates from livestock and companion animals collected in France between 2010 and 2021. Plasmids ( n = 211) were identified from 139 isolates. The major families identified— rep7a , rep20 , and rep10 —were associated with specific resistance genes ( str , cat , blaZ , erm (C)) and exhibited widespread horizontal transfer across different S. aureus sequence types (STs) and animal hosts. In temporal analysis, the rep7a /str and rep7a / cat plasmids circulating in horses were progressively replaced by a rep7a plasmid carrying both str and cat genes. The study also highlighted the presence of mosaic plasmids, which combined elements from different bacterial species/genera, confirming the broad host range of S. aureus plasmids and their ability to acquire ARGs from diverse sources. Moreover, the occurrence of hybrid plasmids (carrying multiple rep genes) underscores the plasticity of these vectors of ARGs. This study emphasizes the need to investigate the mechanisms driving the spread and persistence of antibiotic-resistant plasmids in S. aureus , with a view to developing strategies aimed at combating antibiotic resistance. IMPORTANCE The spread of antibiotic resistance in Staphylococcus aureus is a growing concern, particularly in animals that can serve as reservoirs for resistant strains. This study highlights the crucial role of plasmids in transmitting resistance genes among different animal hosts and S. aureus lineages. The characterization of 329 isolates collected over 10 years revealed how certain plasmid families are associated with specific resistance genes and how they evolve over time. The occurrence of mosaic and hybrid plasmids further underscores the ability of S. aureus to acquire resistance from diverse bacterial sources. These findings provide key insights into the mechanisms shaping antibiotic resistance in this pathogen and emphasize the fact that understanding plasmid-driven resistance is essential for developing effective interventions to limit the spread of multidrug-resistant S. aureus in both veterinary and human medicine
Evaluation of esophageal tubing and buccal swabbing versus rumen cannula to characterize ruminal microbiota in cows fed contrasting diets
No full textInternational audienceRumen microorganisms are primarily essential for feed decomposition and nutrition of the host animal, playing a key role in the health and well-being of cattle as well as the efficiency of milk or meat production. However, they also generate pollutant emissions such as methane. Analysing this microbiota under different farming conditions is therefore essential for optimizing production while minimizing its environmental impact. In this study, with metataxonomic sequencing and qPCR, we analysed the composition of the cow rumen microbiota sampled through the cannula and via esophageal tubing before morning feeding under two contrasting diets, low- and high-starch contents. Buccal swabs were also collected at the same sampling times to assess their potential as a proxy for the rumen microbiota. The two rumen sampling methods resulted in similar taxonomic compositions of bacteria, Archaea, fungi and protozoa and showed similar changes after the diet shift, indicating that the use of esophageal tubing is a reliable method for capturing the microbiota structure and its potential shifts following dietary changes. In contrast, the buccal swabs did not accurately reflect the rumen microbiota under the low- and high-starch diets, even after specific stringent filtering of the buccal sequences. Furthermore, we identified microbial markers of acidogenic challenge, with Dialister spp. also detected in buccal swab samples as potential indicator
Effet dose-dépendant de l’additif alimentaire E471 sur la promotion des lésions prénéoplasiques coliques chez le rat F344
No full textInternational audienceIntroduction et but de l’étudeAu cours des dernières décennies, l'industrialisation de la productionagroalimentaire a connu une progression significative, conduisant à unedisponibilité accrue de produits ultra-transformés (AUT). Ces AUT représententpresque 30% des apports énergétiques journaliers en France. Les transformationsde ces aliments visent à augmenter leur durée de conservation, améliorer le goûtou la texture, mais sont également modifiés par des apports en additifs non indispensables(colorants, émulsifiants, édulcorants…). Un nombre croissant depublications soulèvent la question de l’impact de ces AUT sur la santé humaine,relevant des liens entre leur consommation et une augmentation des risques demaladies chroniques. Bien que les additifs alimentaires aient été autorisés parl’EFSA, les données sur lesquelles ces autorisations se basent ne prennent pastoujours en compte l’évolution des techniques d’évaluation, telles que les cohortesou le microbiote intestinal. Des études récentes ont permis d’identifier de nouveauxrisques associés à l’exposition à ces additifs et ont abouti à l’interdiction decertains d’entre eux (E171). Les émulsifiants, parmi les additifs les plus utilisés,font l’objet de remises en question. Des études récentes montrent que certainsémulsifiants pourraient modifier le microbiote et induire une augmentation del’inflammation, favorisant la survenue de cancer colorectal (CCR). L’étude récentesur la cohorte Nutrinet-Santé a montré que des apports élevés en mono- etdiglycérides d’acides gras (E471) étaient associés à des risques accrus de cancers.Les données précliniques associant émulsifiants et risque de CCR ainsi quel’association épidémiologique entre E471 et risque de cancer, nous ont amené àévaluer l’impact du E471 sur le risque de CCR et à rechercher les mécanismesimpliqués.Matériel et méthodesL'effet d'une exposition chronique à l'E471 pendant 100 jours sur l'écosystème ducôlon et la CCR au stade prénéoplasique a été étudié dans le modèle de rat Fisher344. L'objectif de cette étude était d'établir un lien de causalité dans un modèleanimal entre (i) l'exposition dose-dépendante au E471 et la promotion de lacancérogenèse chez les rats prétraités avec de l'azoxyméthane (AOM). L’additifétait donné à des doses représentatives de l'exposition humaine identifiée dans lacohorte Nutrinet-Santé (D1= dose de 3,8mg/kg pc/j ; D3, D9), (ii) la dose D9 etl'initiation de la cancérogenèse du côlon chez le rat F344 (sans AOM). Lacancérogenèse a été évaluée par dénombrement des lésions prénéoplasiquescoliques (ACF, aberrant crypt foci et MDF, mucin-depleted foci). L'impact globalsur l'écosystème colique a été évalué en mesurant l'activité toxique des eauxfécales des rats sur des cellules coliques murines et en quantifiant la productiondes cytokines pro- ou anti-inflammatoires dans la muqueuse du côlon. Par ailleurs,l’effet de l’E471 sur le microbiote intestinal a également été évalué.Résultats et analyse statistiqueCette étude a démontré dans un modèle animal de CCR que l'exposition chroniqueau E471 induit une augmentation dose-dépendante du nombre de lésionsprénéoplasiques : ACF (P=0,027), MDF (P=0.0015). Nous avons montré uneaugmentation de la toxicité des eaux fécales, ainsi qu'une augmentation de lamicro-inflammation des muqueuses : augmentation du TNFa (P=0,034), ainsi quedes tendances vers une diminution de l’IL10 anti-inflammatoire, une augmentationde l'IL6 pro-inflammatoire et de la protéine C réactive (CRP). Les modifications dumicrobiote suggèrent une augmentation de l’inflammation intestinale. Cetteaugmentation de l’inflammation mucosale est également identifiée chez les rats noninduits, confirmant un effet pro-inflammatoire du E471.ConclusionCette étude confirme les résultats expérimentaux et épidémiologiques sur le risqueassocié aux émulsifiants et démontre pour la première fois un risque associé àl'E471 dans le modèle rat. Nos résultats visent à fournir des données utilisables parles politiques publiques afin d’aboutir à une éventuelle modification de laréglementation concernant l’utilisation du E471, pour protéger le consommateur etparticiper à la définition d’une alimentation humaine plus saine et diminuer lesrisques de cancers digestifs.Soutien financierInstitut Olga TriballatLa Ligue contre le cancer Midi-Pyrénée
DNA-based prediction of eye color in Latin American population applying Machine Learning models
No full textInternational audienceReduction in the costs of DNA sequencing and genotyping allows for the increased availability of databases which can be useful for analyzing the relationship between the human genetic code and visible characteristics, diseases, and behaviors, among others.The aim of this study is to improve the prediction of eye color from genotype by means of several Machine Learning models, using a dataset of 308 volunteers from Buenos Aires, Argentina.The results achieved are competitive and demonstrate the usefulness of artificial intelligence (AI) in the fields of genetics and its application in areas such as health, biometrics and forensics
GenoPHEnix – a European research infrastructure for genome - phenome interactions in sustainable animal production
No full textSession 6 – Methods and technologies for research in the field of sustainable livestock farming abstract 169GenoPHEnixInternational audienceThe European Strategy Forum on Research Infrastructures Landscape analysis identified a critical gap for farm animal genotyping, phenotyping, conservation of genetic resources, and breeding necessitating an integrated pan-European approach. With this specific gap in mind for the creation of a research infrastructure that would provide a long-term, fully collaborative and coordinated institutional framework to the scientific community, the European farm animal genomics and phenotyping research community has resolved to apply for the creation of a new research infrastructure: GenoPHEnix. GenoPHEnix aims to be a pan-European, multi-species, multidisciplinary platform for animal genetic and multiomics resources, phenotyping, genome analyses, and sustainable breeding and management, focused on improving animal welfare, health, resilience, and efficiency. GenoPHEnix builds on 1) the international initiative FAANG (Functional Annotation of Animal Genomes) and the INFRADEV EuroFAANG RI concept development project that works toward the development of the Genome to Phenome approach (G2P), and by 2) the INFRAIA projects AQUAEXCEL 3.0, PIGWEB and SmartCow that have been instrumental in advancing efficient and ethical species-specific phenotyping methods for farmed animals, and in offering transnational access to high-level experimental facilities for the academic and industry research communities. GenoPHEnix will support cutting-edge research in animal science while developing and delivering methods, technologies and innovative approaches to solve the challenges to transform the livestock and aquaculture production systems within the context of One Health and European Competitiveness. GenoPHEnix is designed 1) to sustainably produce and manage healthier farmed animals, with the highest welfare standards; 2) to more accurately exploit animal variability through enhanced phenotyping and genotyping capacity; 3) to contribute to the 3Rs (reduction, refinement, replacement) in animal research by providing suitable models for deep in vitro as well as in vivo phenotyping; 4) to advance the analysis of genome function, combined with the collection of phenotypes and multiomics information at cell, tissue, animal and on-farm/population level resolution; and 5) to provide tools and knowledge for optimal and more precise breeding and animal health considering sustainable management practices, and conservation of genetic diversity. GenoPHEnix will improve the leadership and excellence of European farm animal research community by 1) sharing experimental capacity and providing access for genotyping and non-and minimally invasive large-scale phenotyping of farmed animals in complementary environmental conditions; 2) expanding biobanking capabilities and access to animal genetic resources and cellular models; 3) promoting standardisation and FAIRisation of animal genome and phenome data; 4) seeking synergies with existing projects and other RIs to consolidate European farm animal research in the agri-food domain; 5) training to promote the best practices in farm animal science. GenoPHEnix unites scientific partners from 11 countries, is supported by the European Forum of Farm Animal Breeders and aims, while established, at integrating new partners
Modeling Postoperative Pathologic Ileus in Mice: A Simplified and Translational Approach
No full textInternational audienceBackground Postoperative Ileus (POI) is an iatrogenic complication characterized by a temporary paralysis of gastrointestinal transit, leading to food intolerance, nausea, vomiting, and thus prolonged hospitalization. The severity of POI is influenced by surgical trauma, particularly in intestinal surgeries, which have a high complication rate. To date, no animal model has precisely replicated POI in the context of digestive sutures or anastomoses, procedures common in human digestive resections. Methods To induce POI, mice underwent different surgeries. The surgical procedure involved a midline laparotomy, externalization of the small intestine following external manipulation through moistened cotton applicators, mimicking the surgeon's action when searching for an intestinal lesion. An ileo‐ileal anastomosis was also performed to ensure relevance to human surgical intervention. Intestinal transit was measured by assessing gastric emptying, gastrointestinal transit time (gavage with charcoal, fecal output), and gut motility (isotonic contraction). Postoperative inflammation is assessed in different tissue layers and areas of theintestine. Key Results The externalization of the small intestine with caecum and manipulation for 10 min induced a pathological postoperative ileus. This simple gesture induced a decrease in intestinal transit comparable to the surgical intervention, ileo‐ileal anastomosis. The model showed decreased gastric emptying and reduced ileal muscle contraction, accompanied by neutrophil and monocyte/macrophage infiltration in the external muscularis. Conclusions and Inferences The developed procedure enables inducing postoperative ileus in mice in a very simple and reproducible way that does not require any specific equipment, mimics clinical practice, and reproduces traits of human pathology