Agence de moyen


Titre du projet
Structure diversity, functionality and modulation of milk oligosaccharides in monogastric livestock species: towards optimal development of rabbit and pig holobionts
Nom de l'appel d'offre
Défi/axe ANR
CE20 Biologie des animaux, des organismes photosynthétiques et des microorganismes
Sylvie Combes (GenPhySE, INRAE)
Participants de MaIAGE
Valentin Loux, Mouhamadou Ba, Claire Nédellec, Robert Bossy, Louise Deléger
Partenaires (hors MaIAGE)
Année de démarrage - Année de fin de projet
Date de fin du projet
Building and preserving health is a major issue in animal husbandry. In humans, it is being recognized
that early-life interactions between the microbiome and the immune system have a major influence
on long-term health and development of the holobiont, but little is known in livestock species. In that
context, HoloOLIGO aims at promoting the animal holobiont assembly, optimizing the microbiota
establishment and the intestinal immune system development in the suckling young. Milk provides
the neonate with essential nutritional components and non-nutritional bio-active components. Among
the latter, milk oligosaccharides (MO) target the gut microbiota. As first available prebiotics for
neonates, MO regulate gut microbial composition, promote specific bacteria growth, prevent gut
epithelial adhesion by pathogens, exert an antimicrobial activity and modulate host immune
responses . MO are composed of three to ten monosaccharide units, with 5 building blocks that are
glucose, galactose, N-acetyl-glucosamine, fucose and sialic acid residues. The biological activity of MO
12 dependsontheirstructure.Inhumanmilkmorethan200MOstructureshavebeenidentified while
in bovine milk (the second most studied species) only 50 MO structures have been described, and the 3
MO concentration is 20 fold lower than in human milk . In other mammalian species, data are scarce 45
butrevealanoverallspecies-specificpatternofthestructuraldiversityofMO.Urashimaetal. have hypothesized that the high oligosaccharide diversity in human milk is an evolutionary consequence of the altricial status of human infants that require additional milk-borne protection against pathogens.
Accordingly, our hypothesis for livestock species is that the role of MO is as much important as the maturity of the species is low at birth and the dependence on milk is high. To validate our hypothesis, in a livestock context, we will target two species (pigs and rabbits) that are highly susceptible to digestive disorders after weaning, but with different levels of maturity at birth, including immune, locomotory and sensory capacities, rabbits being less mature than pigs. Moreover, in the context of livestock farming, their dependency on milk differs: at weaning change from milk to solid feed intake is abrupt in pigs while in rabbits the transition is gradual. According to our hypothesis, we expect that MO diversity and its dynamics will strongly differ between the two species. By using these two livestock models, the goal of HoloOLIGO is to elucidate causal links between specific MO structures, the offspring microbiota and immune system. HoloOLIGO will also lay the first foundations to monitor the variability of MO structures in livestock species. To achieve this objective, HoloOLIGO will run for 4 years and is divided into three connected scientific work packages (WP, fig. 1), involving an interdisciplinary consortium of 6 teams that brings together expertise in MO chemistry, informatics, biostatistics, immunology, microbiology, and genetics. It combines in silico data management and knowledge discovery, in vivo and in vitro animal experiments.
Année de soumission