HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
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A refined strategy linking transcriptomics and metabolic models for deciphering chemical induced changes
No full textInternational audienc
Optimization and stability evaluation of a pediatric spironolactone oral suspension: Formulation development and analytical validation
No full textInternational audienc
Multiomics of the intestine-liver-adipose axis in multiple studies unveils a consistent link of the gut microbiota and the antiviral response with systemic glucose metabolism
No full textInternational audienceBackground The microbiota is emerging as a key factor in the predisposition to insulin resistance and obesity. Objective To understand the interplay among gut microbiota and insulin sensitivity in multiple tissues. Design Integrative multiomics and multitissue approach across six studies, combining euglycaemic clamp measurements (used in four of the six studies) with other measurements of glucose metabolism and insulin resistance (glycated haemoglobin (HbA1c) and fasting glucose). Results Several genera and species from the Proteobacteria phylum were consistently negatively associated with insulin sensitivity in four studies (ADIPOINST, n=15; IRONMET, n=121, FLORINASH, n=67 and FLOROMIDIA, n=24). Transcriptomic analysis of the jejunum, ileum and colon revealed T cell-related signatures positively linked to insulin sensitivity. Proteobacteria in the ileum and colon were positively associated with HbA1c but negatively with the number of T cells. Jejunal deoxycholic acid was negatively associated with insulin sensitivity. Transcriptomics of subcutaneous adipose tissue (ADIPOMIT, n=740) and visceral adipose tissue (VAT) (ADIPOINST, n=29) revealed T cell-related signatures linked to HbA1c and insulin sensitivity, respectively. VAT Proteobacteria were negatively associated with insulin sensitivity. Multiomics and multitissue integration in the ADIPOINST and FLORINASH studies linked faecal Proteobacteria with jejunal and liver deoxycholic acid, as well as jejunal, VAT and liver transcriptomic signatures involved in the actin cytoskeleton, insulin and T cell signalling. Fasting glucose was consistently linked to interferon-induced genes and antiviral responses in the intestine and VAT. Studies in Drosophila melanogaster validated these human insulin sensitivity-associated changes. Conclusion These data provide comprehensive insights into the microbiome-gut-adipose-liver axis and its impact on systemic insulin action, suggesting potential therapeutic targets. Cite No
Goblet cells mechanically breach the epithelial barrier in gut homeostasis
No full textAbstract The intestinal epithelium has to maintain a tight barrier against the harsh luminal environment. Absorptive enterocytes have a polygonal and columnar shape, while mucus-producing goblet cells exhibit a round apical cell shape and a bulky body, raising the question of how epithelial integrity is maintained around these cells. Here, we show that goblet cells induce tight junction fractures between neighboring enterocytes under homeostatic conditions in vivo , which are exacerbated during goblet cell hypertrophy, increasing gut permeability. We demonstrate that these fractures arise from a two-component mechanical interaction: goblet cells push and deform adjacent enterocytes, which rupture depending on tissue rheology controlled by myosin II. These findings reveal that the mechanical interplay between goblet cells and neighboring enterocytes is critical for maintaining intestinal epithelial barrier integrity
Observer sans déranger : des accéléromètres pour plonger dans le quotidien d’ovins élevés en plein air intégral
No full textInternational audienceL’accéléromètre est un outil idéal pour recueillir des données d’accélération selon trois axes (X, Y et Z). Dans le cadre du projet WAIT4 (PEPR Agroécologie et Numérique), l’UMR GenPhYSE s’est équipée de 80 accéléromètres de type AX3 de chez Axivity pour définir des indicateurs pertinents de bien-être d’ovins élevés exclusivement en plein air (Figure 1). Cette question de recherche nécessite la réalisation d’une base de données de référence, ou gold standard, qui consiste à filmer le comportement d’animaux portant des accéléromètres pendant plusieurs heures. Cette étape est nécessaire pour aligner les comportements d’intérêt aux signaux issus des accéléromètres et entrainer un modèle d’IA à la détection automatique des comportements à partir uniquement des signaux accéléromètres.Pour ce faire, plusieurs défis techniques ont été relevés.✓ Un système d’attache, de type collier en PETG, a été conçu avec une imprimante 3D de façon à collecter des données de qualité, tout en optimisant la manipulation des accéléromètres et en respectant le bien-être des animaux (Figure 2).✓ Une boîte pour le rangement, le paramétrage, la recharge et la récupération des données de 80 accéléromètres a été fabriquée afin d’optimiser leur gestion sur le terrain (Figure 3).✓ Un coffret électronique a été développé, à partir d’un Raspberry, dans le but d’assurer la synchronisation des horloges des enregistrements vidéo et des signaux accéléromètres (Figure 4).✓ Enfin, un système permettant la gestion des flux vidéo a été conçu afin d’enregistrer le comportement d’animaux grâce à quatre caméras (Figure 4).Ces développements ont permis la réalisation d’un gold standard impliquant 160 agnelles, étape indispensable à la définition d’indicateurs de bien-être à partir d’accéléromètres
Microbial metabolite indole-3-propionic acid drives mitochondrial respiration in CD4+ T cells to confer protection against intestinal inflammation
No full textInternational audienceThe gut microbiota and its metabolites critically regulate immune cell phenotype, function and energy metabolism. We screened a collection of gut microbiota-related metabolites to identify modulators of mitochondrial metabolism in T cells. Here we show that indole-3-propionic acid (IPA) stimulates mitochondrial respiration of CD4+ T cells by increasing fatty acid oxidation (FAO) and amino acid oxidation (AAO), while inhibiting glycolytic capacity. IPA also impacts CD4+ T cell behaviour by inhibiting their differentiation to type 1 and type 17 helper T cell phenotypes. Mechanistically, the metabolic and immune effects of IPA are mediated by peroxisome proliferator-activated receptor-β/δ. The administration of IPA rescues mitochondria respiration in mice with gut bacteria depletion or colitis by enhancing FAO and AAO in colonic CD4+ T cells. Adoptive transfer experiments show that IPA acts on CD4+ T cells to exert its protective effect against inflammation. Collectively, our study reveals that the anti-inflammatory effects of IPA are mediated by metabolic reprogramming of CD4+ T cells toward the enhancement of mitochondrial respiration
Syndrome de renutrition chez les carnivores sauvages, exemple du lynx boréa
No full textWild carnivores, often facing periods of scarcity, injury or diseases limiting their access to food, are susceptible to malnutrition, making refeeding syndrome a major challenge during their management. Due to its patrimonial importance, the Eurasian Lynx (Lynx lynx) is a pertinent example.This state manifests as profound electrolyte imbalances, as well as other potentially fatal metabolic complications. Adequate management is paramount, dictating progressive refeeding, rigorous electrolytic and biochemical monitoring, and specific nutritional supplementation to avoid these vital risks. This study offers a comprehensive understanding of this syndrome and presents a practical guide for care centers, for the effective prevention and management of refeeding syndrome, adapted to the unique physiological requirements of these species.Les carnivores sauvages, souvent confrontés à des périodes de disette, de blessures ou de maladies limitant leur accès à la nourriture, sont sensibles à l’état de dénutrition, faisant du syndrome de renutrition un défi majeur lors de leur prise en charge. Par son importance patrimoniale, le Lynx boréal (Lynx lynx) en est un exemple pertinent. Cet état critique se manifeste par des déséquilibres électrolytiques profonds ainsi que d’autres complications métaboliques potentiellement fatales. Une prise en charge adéquate est primordiale, dictant une réalimentation progressive, un suivi électrolytique et biochimique rigoureux, mais également une supplémentation nutritionnelle ciblée pour déjouer ces risques vitaux. Cette étude offre une compréhension approfondie de ce syndrome et présente une fiche pratique destinée aux centres de soins, pour la prévention et la prise en charge efficace du syndrome de renutrition, adaptée aux exigences physiologiques uniques de ces espèces
Towards collective biosecurity: a participatory approach in French communities of poultry farmers
No full textInternational audienc
Putative cutaneous adverse drug reaction suspected to be secondary to drug excipient and responding to brand change of pimobendan in a dog with hyperkeratotic erythema multiforme
No full textInternational audienceAbstract A 16‐year‐old, spayed, female mixed terrier dog was presented with a 4‐month history of hyperkeratotic, pigmented raised papules and plaques. Histopathological examination of skin biopsies revealed a hyperplastic panepidermal cytotoxic lymphocytic dermatitis compatible with hyperkeratotic erythema multiforme. The patient had started treatment with pimobendan 2 weeks before the appearance of the lesions. A brand change of pimobendan resulted in complete healing of the lesions within 3 weeks without any treatment. This case highlights the importance of considering excipients as potential sources of cutaneous adverse drug reactions
