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Perinatal nutrition plays a decisive role in controlling gut bacterial primo-colonization and, thereby, is an important driver of the development and maturation of intestinal immunity. Since a short-chain fructooligosaccharide (scFOS) prebiotic was known to modulate microbiota, our study evaluated effects of such supplementation on intestinal immunity development and functionality of piglets. Sows received a standard diet supplemented with scFOS or not (CTRL) for the last third of gestation and the entire lactation. Intestinal immune system maturation was assessed at PND 21 during lactation. At postnatal day (PND) 28, piglets were weaned on a CTRL or scFOS diet for four to seven weeks. Then, during the post-weaning period, two vaccine challenges were performed individually; one vaccine directed against Influenza respiratory virus and the other directed against the intestinal bacterium Lawsonia intracellularis, to assess immune responsiveness later in life. Maternal scFOS supplementation stimulated the development of the offspring intestinal immune system before weaning. Such improvement induced beneficial effects on its functionality, later in life, by enhancing local defense mechanisms (number of goblet cells and cytokine secretion) and responsiveness to a bacterial vaccine challenge (production of specific antibodies). Interestingly, the maternal scFOS supplementation improved the immune response to L. intracellularis vaccine, but not that to the vaccine directed against the Influenza respiratory virus. The direct scFOS supplementation of weaned piglets increased the response to Influenza challenge, but not to L. intracellularis vaccine. Thus, the window of nutritional exposure to scFOS (maternal versus post-weaning) conditioned the consequences on the immune system. Our results highlight the role played by early prebiotic supplementation to optimize intestinal immune functionality in piglets to obtain health benefits., La nutrition périnatale joue un rôle décisif dans la primo-colonisation bactérienne et constitue un facteur important pour la maturation de l'immunité intestinale. Les fructooligosaccharides à courte chaîne (FOScc) étant des prébiotiques connus pour moduler le microbiote, notre étude a évalué les effets d’une telle supplémentation sur la fonctionnalité du système immunitaire intestinal des porcelets. Des truies ont reçu un régime supplémenté en FOScc ou non (CTRL) en fin de gestation et pendant la lactation. La maturation du système immunitaire intestinal a été évaluée à 21 jours. Au sevrage à 28 jours, la moitié des porcelets de chaque portée a reçu le régime CTRL ou FOScc pendant 4 à 7 semaines. En post-sevrage, deux challenges vaccinaux ont été effectués séparément, un premier vaccin dirigé contre la bactérie intestinale Lawsonia intracellularis et le second contre le virus respiratoire Influenza afin d’évaluer la réactivité immunitaire ultérieure. La supplémentation maternelle en FOScc a stimulé le développement du système immunitaire du porcelet allaité. Une telle amélioration a entraîné des effets bénéfiques sur sa fonctionnalité ultérieure, objectivée par un renforcement des mécanismes de défense (cellules à mucus et sécrétion de cytokines) et de la réponse vaccinale (anticorps spécifiques). La supplémentation maternelle en FOScc a amélioré la réponse immunitaire au vaccin contre L. intracellularis, mais pas celle contre le virus Influenza. La supplémentation directe en FOScc en post-sevrage n’a augmenté que la réponse vaccinale au virus Influenza. Par conséquent, la fenêtre d’exposition nutritionnelle aux FOScc (maternelle versus post-sevrage) conditionne les effets sur le système immunitaire. Nos résultats soulignent le rôle joué par la supplémentation précoce en prébiotiques pour optimiser la fonctionnalité de l’immunité intestinale des porcelets afin d’obtenir des bénéfices sur la santé.

Session Scientifique 1 : “Immunomodulation”Session Scientifique 1 : “Immunomodulation”; International audience; Impact of food additive (prebiotic) and food contaminant (mycotoxin) in the maternal diet onto the ontogenesis and responsiveness of mucosal immune system. IAD 2016 - 10. Journées du Réseau Français "Immunologie des animaux domestiques"

Early life nutrition impacts durably several physiological and metabolic functions and is a risk factor for the development of metabolic disease in adults (obesity, type 2 diabetes, hypertension, …). This theory of nutritional imprinting or Developmental Origin of Health and Disease established by Barker in the late 80’s (1) has been reinforced by experimental data on organs and tissues directly involved in the pathophysiology of the metabolic syndrome (liver, adipose tissue, pancreas…) (2). The gut has got little attention in this context so far. Yet, evidences for a role of the gut in the pathophysiology of metabolic diseases in adults, especially with gut microbiota and barrier function maladaptation to a high fat diet, have emerged (3-4). The structure of the gut microbiota is established and the mucosal immune system programed in early life. This postnatal development is not hard-wired and is influenced by environmental and nutritional factors. Man can hypothesize that this flexibility in acquisition of the microbiota and education of the gut immune system in early life would be long-lasting and induce distinct response to a high fat diet later in life. There are already several evidences that early life environmental factors including stress such as maternal deprivation or chemical contaminants such as bisphenol A dramatically impact adult response to gut inflammation or visceral painful stimuli in models of inflammatory bowel disease and irritable bowel syndrome. Recently, evidences have also emerged that nutritional factors, including energy, fat and fatty acids, protein, and micronutrients imbalances during early life have remnant effects of gut function in adults with alterations in microbiota, intestinal barrier function and/or defense systems. Examples of such long-term effects on the gut will be provided, focusing on piglet model and adaptation to a high fat diet. Those emerging data challenges neonatal nutrition which, apart from its traditional role as a supplier of building blocks for growth, may play another, yet potentially crucial role in shaping the individual’s future life, impinging on the risk of disease decades later on.

Background: Peripartum antibiotics are thought to have long-lasting negative consequences on intestinal barrier function, immune system development and long-term health, e.g. allergy. Various kinds of stress (e.g. nutrition, environment) can be deleterious to gut barrier function. We have shown that broad spectrum antibiotic administration to sows around parturition alters various facets of gut barrier in their offspring during development and in adulthood. We tested with this model the hypothesis that early administration of a probiotic to offspring can modulate gut barrier function in young adults depending on diet and stressor. Methods: Sows (n=20) received amoxicillin orally (40mg/kgBW/d) around parturition (day-10 to day+21) in order to induce gut barrier disturbances in offspring. Piglets from half of the litters received orally a probiotic suspension (Lactobacillus sobrius, 108/ml, 1 ml/pig and intervention, PROB) at birth and then three times a week until postnatal day PND21. Offspring were reared under the sow until weaning at PND28. They were reared with a similar diet until PND141. Then, each group was split into two halves. One half in each group remained on the control (low fat, LF 2%) diet while the other halves were fed a high fat (HF, 11%) diet. Pigs were sacrificed at PND169 and pieces of ileum and colon were collected and mounted in Ussing chambers (UC). UC treatment included control, oxidative stress (monochloramine) and mast cell degranulation stress (48/80). Mucosal para- and trans-cellular permeabilities (PCP, TCP) were measured using FD4 and HRP, respectively. Results: Early PROB supplementation had no effect on offspring basal ileal and colonic permeabilities. Ileum from PROB pigs fed LF diet displayed reduced PCP in oxidative (P,0.05) and degranulation (P,0.10) conditions. No differences between PROB and CTL were seen for colonic PCP. Contrasting with this, ileal TCP was much higher (x 2 to 3) in PROB pigs with both LF and HF diets (P ,0.01) after degranulation stress. An interaction (P,0.10) between early PROB treatment and adult diet was observed for TCP after oxidative stress (decrease with LF, increase with HF). Colonic TCP was increased after both oxidative and degranulation stress in PROB pigs fed LF (but not HF) diet (P ,0.05). Conclusion: Our data in the swine model suggest that probiotics provided early to gut barrier-disturbed offspring born to mothers treated with broad-spectrum antibiotic around parturition can contribute to long-term modulation of gut barrier function following stress. However, the responses are complex and depend on gut site, and diet composition and type of stressor in adluthood. Work is in progress to investigate long-term changes in gut microbiota composition induced by early probiotic administration.

Session : Nutrition & EndoscopySession : Nutrition & Endoscopy; Presence of milk phospholipids and milk lipids modified the immunomodulatory properties of infant formula in neonatal pigs. 4th World Congress of Pediatric Gastroenterology, Hepatology and Nutrition

International audience

International audience

Session : AlimentationSession : Alimentation; The main objective of this study was to evaluate the effect of extruded linseed (rich in alpha‐linolenic acid, ALA) in the sow diet on the intestinal barrier function of piglets. Twelve sows (Large White x Landrace) were divided into two groups: the first one received a diet containing sunflower oil (ALA3 with ALA represented 3% of total fatty acids) and the second received a diet containing extruded linseed (ALA27 with 27% of ALA) during gestation and lactation. Intestinal paracellular permeability was assessed in Ussing chamber on piglets at weaning (28 days of age). Intestinal sensitivity to lipopolysaccharides (LPS) was also determined at weaning, using jejunal explant cultures, through pro‐inflammatory cytokines interleukin 8 (IL8) and tumor necrosis factor alpha (TNFα) secretion in response to different doses of LPS. Jejunal permeability of ALA27 piglets was higher than that of ALA3. Jejunal sensitivity to LPS was lower in ALA27 piglets despite the higher intestinal permeability. In conclusion, incorporation of extruded linseed in the sow diet during gestation and lactation modified the intestinal barrier function of piglet at weaning. However, this higher intestinal permeability was not associated with immediate consequences on the inflammatory status of piglet mucosa.

National audience

*INRA C.R.Tours, Unité Pathologie Aviaire et Parasitologie, 37380 Nouzilly (FRA) Diffusion du document : INRA C.R.Tours, Unité Pathologie Aviaire et Parasitologie, 37380 Nouzilly (FRA) Diplôme : Dr. d'Université