Impact of early life influences on aspects of physiology and production in pigs

Transcription

1 LifeStart Global Swine Symposium, Eindhoven, The Netherlands Impact of early life influences on aspects of physiology and production in pigs Dr. John Pluske School of Veterinary and Life Sciences

2 Foetal weight as a function of the number of days in gestation (McPherson et al., 2004; J. Anim. Sci. 82, )

3 Distribution of within-litter birth weight variation and its relationship to parity Larger numbers born alive is also associated with increased within-litter birth weight variation (Zindove et al., 2014; S. Af. J. Anim. Sci. 44, 80-84) CVBWT: coefficient of variation in birth weight (%)

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5 Lifetime and post-wean determinants of performance Major determinants of immediate POST-WEANING performance were age and weight of pigs at weaning Age at weaning had little or no influence on growth performance but influenced fat deposition, Pigs weaned at 14 d of age had more backfat than pigs weaned at 28 d of age Key determinant of LIFETIME performance was the weight of the pig at weaning or, by inference, at birth, But, such data does NOT account for 100% of variation in weight at slaughter, mortalities, lean % at slaughter, etc.

6 Birth weight of pigs impacts their subsequent growth path (Václavková et al., 2012; Res. Pig. Breed. 6, 1-4)

7 kg / pig weaned Mortality,% Increasing weaning age is associated with improved grow-finish production ,1 Trial 1 Trial 2 Trial 1 Trial ,4 116,2 113, ,6 7, ,6 6, , ,5 5 3,6 3,9 4 3, ,5 18,5 21,5 Wean age,d 2, ,5 18,5 21,5 Wean age,d Increasing weaning age from 12 d to 21.5 d of age increased weight sold per pig weaned by / kg for each day increase in weaning age (Main et al., 2004; J. Anim. Sci. 82, ) (Trial 1 used 2,272 pigs, Trial 2 used 3,456 pigs)

8 Weaning age affects gut barrier function As weaning age is increased, intestinal barrier function is improved (indicated by improved TER and lower permeability) [Values are means ± SE, n = 6 pigs per weaning age treatment] (Smith et al., 2010; Am. J. Physiol. 298, G352-G363)

9 Colostrum - the first secretion Colostrum is a complex mix of nutrients and chemical constituents Ready source of highly digestible lipid, lactose, protein and minerals Colostrum is the major source of immunoglobulins after birth Colostrum (and milk) provide energy, nutrients and growth factors needed by the piglet to grow, survive, and allow for the growth and development of the gastrointestinal tract Colostrum is vital for thermoregulation, immune development, and survival

10 Piglets drinking less colostrum have higher risk of dying (Quesnel et al., 2012; Livest. Sci.146, )

11 Absence of luminal nutrition (via TPN) affects gut growth and function 48 hours feeding Enteral Protein fractional synthesis rate in jejunum of piglets Rates of villous and crypt epithelial cell apoptosis in the jejunum TPN (Niinikoski et al., 2004; J. Nutr. 134, ) TPN: total parenteral nutrition

12 Sow parity influences piglet IgG levels at h after birth (Cabrera et al. 2012; J. Anim. Sci. Biotech. 3:42)

13 Fattening mortality (%) Piglets that suckled on gilts have higher mortality during the fattening phase than those suckled on sows Gilt Sow 2 0 Suckled (Pineiro et al., 2006; J. Anim. Sci 84, Suppl. 1/J. Dairy Sci. Vol. 89, Suppl. 1)

14 Can we increase IgG levels for piglets? Bland et al. (2001): Increasing vitamin A, C and E levels (1-3 times NRC) in diets for sows increased plasma IgG levels in piglets 12 and 24 h after suckling Mitre et al. (2005): Sows given shark liver oil (SLO) (source of n-3 PUFA and alkylglycerols) from d 80 of gestation and then in lactation Colostrum from sows, and serum of piglets from sows, fed SLO had higher biomarkers of immune function Piglets sucking sows fed SLO grew faster in lactation

15 Immunoreactive growth factors (ng/ml) are markedly higher in colostrum than in milk Milk Colostrum Time of sample (d post-partum) EGF Insulin IGF-I IGF-II TGF (From Xu et al., 2002; In Biology of Intestine of Growing Animals, pp )

16 Growth and morphology of jejunum in piglets weaned at birth and fed for 4 d with or without recombinant IGF-1 Treatment Item Milk replacer Milk replacer + rhigf-1 P-value Weight, g kg -1 BW Length, cm kg -1 BW DNA, mg kg -1 BW Protein, mg kg -1 BW Villous height, m Crypt depth, m (Burrin et al., 1996; Am. J. Physiol., 270, R )

17 Relationship between plasma IGF-I and average growth rate for young pigs given liquid diets with either colostral isolate or whey protein Plasma IGF-I (ng/ml) Colostral isolate Whey protein Growth rate (kg/d) (Van Barneveld and Dunshea, 2011: Asian-Aust. J. Anim. Sci. 24, )

18 Bacterial epidermal growth factor (EGF) Powerful growth factor stimulating gut development in young pigs; present in milk, saliva and blood Porcine EGF gene has been isolated, inserted in Lactococcus lactus and modified to increase expression Gut mucosa (stained for cell proliferation) (Bedford et al., 2014; J. Biotech. 173, 47-52)

19 Villous height (um) Lactococcus lactis (LL) engineered to express EGF improves gut structure in weaned mice d c d b c a b b a a c Control LL rhegf LL-EGF d 0 Ileum Jejunum Ileum (Newly weaned mice; twice daily oral dosing 0.75 x 10 9 CFU of LL or LL-EGF, PBS for control and rhegf, 50 ug/kg of rhegh) (Cheung et al., 2009; Am. J. Clin. Nutr. 89, )

20 Three treatments: 1.Blank M17GE media (Control) 2.Complete EGF-LL fermentation product (Ferm) 3.Supernatant of EGF-LL fermentation product, after removal of EGF-LL (GMO component) (Supern) Treatments mixed with feed after weaning Ferm and Supern groups received volumes equal to 80 μg EGF/kg BW/day of EGF (Bedford et al., 2014; J. Biotech. 173, 47-52)

21 A bovine colostrum powder rich in IgG and IGF-I and IGF-II, fed for 10 d after weaning, reduced days to slaughter * Pooled SD = ** ** Control 50 g/kg 100 g/kg (Pluske et al., 1999; Manipulating Pig Production VII, p. 256)

22 Summary: Perinatal factors influencing development and maturation of the gut Prenatally, maturation of gut function is likely more dependent on internal signals (genetic, endocrine) than on luminal stimuli (enteral nutrients and bioactive factors) Postnatally, the digestive and absorptive capacity is highly sensitive to and regulated by changes in enteral diet input and colonization of the gut by bacteria

23 The piglet transitions from colostrum to milk, but

24 Is sows milk the best food for the sucking piglet? 1. Availability of sows milk restricts growth, Studies in artificially-reared piglets show that potential is at least 450 g d -1 between birth and 21 d Sow needs to produce kg milk d -1 to meet piglets demands between birth and 21 d 2. Composition restricts growth, P:E (protein:energy) ratio lower than required for maximum growth; 0.9 g MJ GE -1 vs 0.8 g MJ GE -1 (in milk) Lacking in some essential amino acids (arginine?) Sows milk has evolved for fat deposition

25 Effect of birth weight and milk replacer Wolter et al. (2002), on lifetime performance 2 x 2 factorial arrangement of treatments in the preweaning period, Birth weight: Heavy ± 0.09 kg vs. Light ± 0.07 kg) weight groups +/- Milk replacer: d 3 of lactation to weaning (21 d) Pigs weaned at 21 d of age and treated identically until slaughter at 110 kg BW

26 Birth weight and milk replacer influence pre-wean performance Birth weight Milk replacer Heavy Light Suppl. Un-Suppl. Birth weight, kg 21-day weight, kg ADG, wean-21 d *** *** *** (P=0.16) *** kg milk powder / litter (Wolter et al., 2002; J. Anim. Sci. 80, ) *

27 Birth weight and milk replacer influence whole-of-life performance Birth weight Milk replacer Heavy Light Suppl. Un-Suppl. ADG, wean to 14 kg (g) ADG, wean- 110 kg (g) FI, wean-110 kg (g) *** *** *** Days, birth to 110 kg BW (Wolter et al., 2002; J. Anim. Sci. 80, ) *** **

28 Do pigs exhibit compensatory growth? Compensatory (or catch-up) growth: the growth of an animal fed ad libitum after a period of nutritional stress, which is higher then the growth of a genetically-identical animal in the same environment at the same body weight during normal growth (Hogg, 1991) In lactation, the relative deficiency of protein (in the milk) and the restriction in the quantity of intake that together limit growth, may represent a situation whereby compensation could be effected Campbell and Dunkin (1983 a, b, c), Evidence of compensation in very young pigs (1.8-2 kg) when deprived of protein and energy or both, even with fixed intakes of food Does skim milk powder, or other milk products, having a high protein content and good EAA balance allow young pigs to compensate for nutrient deficiencies in sows milk?

29 Feeding liquid milk (skim milk) for a short period around weaning improves growth to L: P < 0.05 M: P < 0.05 SED: d of age 10% kg Pellets Pellets+Milk Pellets Pellets+Milk Post-Wean (M) Sow s milk (Dunshea et al., 1999; Aust. J. Agric. Res. 50, ) Sow s milk + milk Lactation (L)

30 Establishment of the gastrointestinal tract microbiome

31 Does a healthy piglet start with a healthy sow? Establishment of GIT microbiota after birth (usually quite stable after initial colonization) plays an important role in the development of the neonatal gut and its immune system Mother s microbiota is shared to a large degree (usually) by the offspring during the first days of postnatal life

32 Fecal bacteria populations of sows, and progeny on d 7, and 61 of age, taxonomically classified at Family level (Hinkle, 2012; PhD Thesis, University of Nebraska) (Significant changes by day noted with a (*) following Family classification)

33 Differentially expressed genes of the small intestinal epithelium in conventional vs. germfree piglets Unknown genes (Caesarian-derived germfree newborn piglets colonized with adult swine feces at h post-partum) (223 genes differentially expressed (P < 0.05) in CONV vs. GF; 170 genes upregulated and 53 genes downregulated) (Chowdhury et al., 2007; BMS Genomics 8, 215 )

34 Colonization by gut bacteria drive development of the immune system (Reproduced with kind permission from Professor D. Kelly) (Bauer et al., 2008 ; Curr. Issues Intestinal Microbiol. 7, 35 52)

35 Does a healthy piglet start with a healthy sow? However, early disturbances of microbial colonization, e.g., hygienic status of rearing environment, antibiotic treatment of sows, may have negative consequences for developmental of the gut of the offspring Relevant to sows because antibiotics are frequently used for controlling infections, e.g., of genito-urinary tract and (or) mammary gland peri- or post-partum Piglets are sometimes also given antibiotics after birth

36 (Cell 158, ; 2014)

37 Mice received low dose penicillin (1 μg/g BW) continuously for life (20 wk) beginning at weaning (day 28 of life; LDP-w) or from birth (LDP-b) Control mice had no penicillin exposure Mice at 4 wk of age (Cox et al., 2014; Cell 158, ) Ileal expression of transcription factors representative of four T-helper cell lineages reduced with LDP at 8 wk of age

38 Long-lasting effects of postnatal antibiotic treatment and routine handling on gut microbiota composition Study design: Piglets of 16 sows divided into three groups in lactation (T1, T2, and T3): T1: no disturbance, piglets only handled at bleeding at d 8, 55, and 176 T2: piglets injected s.c. with 0.1 ml Tulathromycine (2.5 mg/kg) at d 4 after birth T3: piglets injected s.c. with 0.1 ml Tulathromycine at d 4 after birth and received standard management procedures (i.e. docking, clipping and weighing) Shannon diversity index in microbiota in three groups on day 55 and 176 Differences also in intestinal gene expression, e.g., in immunological processes, and differences at the transcriptomic level likely due to microbiota-induced differences in immune programming during the neonatal period (Schokker et al., 2015; PLOS ONE 10(2): e )

39 Proposed model for the role of maternal microbial transmission in early life programming and neurodevelopment (Jašarević et al., 2015; Neurobiol. Stress 1, 81-88)

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41 Altering the n-3:n-6 ratio in the sow s diet can affect barrier function in the progeny Linseed oil 1.5% gestation 5.5% lactation

42 But - what if the composition of the microbiome could be influenced in utero?

43 Is the foetus sterile? A fetus has been considered microbiologically sterile, however, some recent discoveries point to the initiation of pregnancy as the beginning of bacterial exposure for the developing foetus Bacteria from maternal gut and/or urogenital region, such as Enterococcus spp. and Lactobacillus spp., have been isolated and/or detected in umbilical cord blood, amniotic fluid, meconium and placental fetal membranes, without clinical evidence of infection or inflammation in the mother-infant pair (Jiminez et al., 2005) Findings suggest that term fetuses are not sterile, and that a mother-to-fetus efflux of commensal bacteria through the placental barrier may occur to colonize the foetal GIT

44 Bacterial isolates identified from umbilical cord blood (samples collected during programmed elective cesarean births) (Jiménez et al., 2005; Curr. Microbiol. 51, ) Enterococcus faecium, Propionibacterium acnes, Staphylococcus epidermidis, Streptococcus sanguinis

45 What is the impact of the early life environment on gut development and whole-of-life performance?

46 Rearing environment affects the microbiome and gut development [Black bars: low-hygiene (farm-reared) piglets; open bars: high-hygiene (isolator-reared) piglets] Ileal flora of farm pigs more variable after d 5, reflected in a lower similarity index over time (Inman et al., 2010; Clin. Exp. Immunol. 160,

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48 Indoor, Outdoor and Isolator Environments (With kind permission from Professor Kelly)

49 Early-life environment alters microbial mucosa-associated diversity at 56 d of age (Mulder et al., BMC Biology 2009, 7:79)

50 Differentially expressed genes in the ileum of animals housed in different environments Specifically associated with inflammatory genes, e.g. Type-1 IFN (Mulder et al., 2009; BMC Biology 7:79) (IR, isolator reared; IN, indoor reared; OUT, outdoor reared)

51 But do these differences impact upon production, in particular whole-of-life performance?

52 Rearing method in lactation changes the form and composition of stomach contents at weaning Indoor Outdoor

53 Overall aims of experiments 1. To examine the post-weaning and whole-of-life performance of, Indoor- and outdoor-born and raised piglets, that were reared from weaning to finish in, Conventional or deep-litter pens 2. To investigated the nature of the solid feed offered to piglets in lactation on post-weaning and whole-of-life performance

54 Effects of type of feed offered to Payne et al. (2005), piglets in lactation Investigated the type of solid feed offered to piglets in lactation on whole-of-life performance, gastrointestinal tract health and development, and carcass characteristics Hypothesis: Is exposure in the pre-weaning period to substrates encountered by outdoor-born and reared piglets beneficial to whole-of-life performance?

55 Effects of type of feed offered to 24 multiparous sows farrowed indoors All piglets given 200 mg Fedextran Litters allocated, No creep feed Commercial creep feed Outdoor mix (25 parts soil, 5 parts sow feed, 1 part straw) Creep feed offered from d 7 to weaning at d 28 piglets in lactation

56 (Payne et al., 2005, Manipulating Pig Production X, p. 158) Pre-weaning exposure to an outdoor mix improved carcass traits at slaughter No effect on pre- and post-weaning production Offering outdoor mix for 21 days in lactation increased, Carcass weight Dressing percentage at slaughter kg / % * * P = (carcass, kg) P = (dressing %) Carcass weight (kg) Dressing (%) 64 Gain, birth to finish ( kg), was 677, 677 and 693 g/day (P = 0.238) 62 No creep feed Creep feed Outdoor 'mix'

57 Conclusions Factors occurring early in life (prenatal, postnatal, after weaning) can have a profound influence on standard industry measures of production and performance Growth and development of the gut (prenatal, postnatal, after weaning) integral to whole-of-life industry measures Environmental, nutritional and (or) psychological interventions at critical times of the young pig s development can potentially alter growth and development, e.g., heat stress in gestation

58 Gestational treatment affected circulating insulin concentrations in piglets Gestational treatment had a tendency to affect concentrations (P = 0.09) Concentrations elevated in pigs from HS dams in first half of gestation compared to TN piglets (P = 0.01) (Boddicker et al., 2014; PLoS ONE 9(11): e110859)