Peri-partum scfos supplementation modulates development and activity of the immune system of suckling piglets

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EAAP 2013 Peri-partum supplementation modulates development and activity of the immune system of suckling piglets C. Le Bourgot 1, S. Ferret-Bernard 1, S. Blat 1, E. Apper-Bossard 2, L. Le Normand 1, F. Respondek 2, I. Le Huërou-Luron 1 1 INRA UR 1341 ADNC, Saint Gilles, 2 TEREOS-SYRAL, Marckolsheim, France

Background Immune system in early life Birth Weaning GESTATION LACTATION POST-WEANING Immature immune system Importance of Gut Associated Lymphoid Tissue (GALT) Mature immune system Maternal microbial exposure Colostrum and breast feeding Exogenous antigens

Background Prebiotics Definition : A selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well being and health (Gibson et al. 2004) Dietary components Short-chain fructooligosaccharides Intestinal microbiota Bifidobacteria and Lactobacilli Swanson et al., 2002 Howard et al., 1995 Bacteria metabolites SCFA (butyrate, acetate, propionate) Berg et al., 2005 Tsukahara et al., 2003 G = glucose F = fructose Sucrose Fructofuranosidase Intestinal effects GF2 GF3 GF4 Improvement of barrier function Reduction of intestinal infections Modulation of intestinal peptide production Modulation of immune system Gibson et al., 2004; Cani et al.,2009

Background Immunity modulation by Effects on adults: augmentation of IgA concentration in serum (Swanson et al., 2002) increase of IgA secretion in intestinal mucosa (Hosono et al., 2002) improvement of cytokine responses by Peyer s patch cells (Hosono et al., 2002) Effects on mothers and offspring: augmentation of IgM level in colostrum and milk and modulation of Ig concentration in serum of puppies (Adogony et al., 2007) Global trend for stimulating immunity following supplementation, but less is known about maternal immune transfer and effects on GALT in piglets

Hypothesis MOTHER OFFSPRING GUT Peri-partum supplementation Microbiota Microbiota Transferred bacteria Microbiota Lumen Epithelium Colostrum and milk Immune system B-cells APC T-cells Mucosa APC : Antigen-presenting cells

Objectives Determine the impact of maternal dietary supplementation during gestation and lactation on: Acquisition of passive immunity in the suckling piglets Development of intestinal immune system in the suckling piglets Response to vaccination in the weaned pigs

Protocol CTRL Gestation Standard Birth Lactation Standard Weaning Standard + n=17 + + Standard + n=17 d28 d77 d35 d56 Influenza vaccine (Gripovac 3 )

Performances of sows and piglets kg kg SOWS 290 280 270 260 250 240 230 220 210 PIGLETS 10 9 8 7 6 5 4 3 2 1 0 Weight d-35 d-7 d14 d28 Weight d0 d7 d14 d21 d28 CTRL CTRL mm 24 22 20 18 16 14 12 10 d-7 d14 d28 Back fat thickness # # CTRL #: p <0.10 supplementation tended to increase back fat thickness in sows during the lactation

Objectives Determine the impact of maternal dietary supplementation during gestation and lactation on: Acquisition of passive immunity in the suckling piglets Development of intestinal immune system in the suckling piglets Response to vaccination in the weaned pigs

Colostrum and milk immune quality 18 16 14 * IgA 160 140 120 IgG CTRL mg/ml 12 10 8 6 4 * CTRL mg/ml 100 80 60 40 2 0 colostrum d6 milk d21 milk 20 0 2 1 0 colostrum d6 milk d21 milk supplementation improved IgA levels in colostrum = improvement of passive immunity *: p <0.05

Objectives Determine the impact of maternal dietary supplementation during gestation and lactation on: Acquisition of passive immunity in the suckling piglets Development of intestinal immune system in the suckling piglets Response to vaccination in the weaned pigs

Intestinal immune system of suckling piglets (ileal PP d21) NEONATES Maturation of the GALT depends on: Humoral-mediated immunity siga secretion Cell-mediated immunity Balance Th1/Th2 *p<0.05 ** p<0.01 * IFNγ ** IL-10 (pg/m l) IL-10 ilpp cells cultured in basal condition for 7d ilpp cells stimulated with ConA (5µg/ml) for 72h Maternal diet improved maturation of GALT after birth that confers a better response against pathogens

Objectives Determine the impact of maternal dietary supplementation during gestation and lactation on: Acquisition of passive immunity in the suckling piglets Development of intestinal immune system in the suckling piglets Response to vaccination in the weaned pigs

Vaccine challenge in weaned pigs Influenza vaccine (Gripovac 3 ) Birth Weaning CTRL Standard Standard Standard + + + Standard + No effect of maternal diet d28 d35 1 st injection d56 Boost injection d77 Serum collection: measure of specific anti-flu IgA and IgG

Vaccine challenge in weaned pigs Influenza vaccine (Gripovac 3 ) Δ (DO) 0,020 0,018 0,016 0,014 0,012 0,010 0,008 0,006 0,004 0,002 0,000 Specific anti-flu IgA Weaning diet CTRL CTRL Vaccine - - + + Δ (DO) 0,16 0,14 0,12 0,10 0,08 0,06 0,04 0,02 0,00 Specific anti-flu IgG * ** Weaning diet CTRL CTRL Vaccine - - + + Direct supplementation improved the specific anti-flu IgG concentration in serum of weaned pigs * p<0.05 ** p<0.01

Summary Maternal supplementation during perinatal period: Tended to increase body reserves of sows: improvement of reproductive performances Higher [IgA] in colostrum : enhancement of passive immunity Increased siga and IFNγ secretion by ileal PP cells: better development and maturation of the mucosal immune system Direct supplementation after weaning: Increased specific anti-flu [IgG] in serum: improvement of vaccine response

Thank you for your attention We thank : Maurice Alix, René Bouetard, Daniel Boutin, Bernard Carrissant, Hervé Demay, Fabien Guérin, Georges Guillemois, Christophe Jaeger, Jerôme Liger, Michel Massart, Henri Renoult, Jean-François Rouaud, Gérard Savary, Yannick Surel, Patrick Touanel