Prenatal and neonatal gut maturation

Transcription

1 Department of Veterinary Clinical and Animal Sciences Prenatal and neonatal gut maturation Thomas Thymann Comparative Pediatrics and Nutrition Dept. Vet. and Animal Science

2 P.W. Nathanielsz Whom signals to whom? About what? And when?

3 Variation in maturity and weight at birth: Optimal gestional length: 115d 118d Large litters 115d 116d 116d 113d 114d 115d

4 Sted og dato Slide 4 Vanderhaeghe et al., Reprod Dom Anim 46: Enhedens navn

5 Enhedens navn Effective breeding program toward large litter sizes Sted og dato Slide 5

6 Enhedens navn Sted og dato Slide 6 Flemming Thorup, SEGES

7 Development of blood cortisol before birth 140 Fetal cortisol (ng/ml) Piglet Lamb Foal Calf (modified from Silver & Fowden, 1995) Days before birth (days) BIRTH

8 Organ weight relative to body weight, g/kg 6 5 Stomach In pigs, - large increase after birth 4 3 Birth Small intestine 1,6 1,2 Pancreas , Age before and after birth (days) Sangild et al.

9 Enteral nutrition during fetal life Fetus-colostrum Fetus-formula (Am. J. Physiol. 281, 2001)

10 Response to the first enteral milk: Intestinal weight (g/kg) Unfed Colostrum (15 ml/kg/3h for 24h) Term Fetal (Am. J. Physiol. 281, 2001)

11 Distal intestine Caecum- Colon Premature pig Colostrum Premature pig Formula NEC Riskfactors of necrotizing enterocolitis (NEC) : 1) prematurity, 2) formula and 3) microbial colonization

12 Immediate postnatal survival, - what are the challenges and what do we do? Respiration Oxygen, surfactant, and pulmonary caffeine, ventilation expansion Provision Active thermoregulation of external heat Adrenalin Circulatory Dopamin changes Atropin Steroid Blood transfusion Blood pressure Fluid support and perfusion NSAID Colostrum Immunization intake Germ free Infection/sepsis Antimicrobials resistance Probiotics Prebiotics Mothers Nutritionmilk Donor milk Formula, PN

13 Preterm Pig Intensive Care Unit to help answer difficult questions! 25 incubators Respiratory support Temp./moisture control Low microbial exposure Parenteral/enteral nutrition 24 hour camera surveillance

14 Gut responses TPN(n=6 14) Infant Formula (IF, n=8 15) Bovine Colostrum (BC, n=7 13) 15% * 60% NEC ** 0% Lac/Man-ratio * Gut permeablity % of animals % ** 93% Diarrhea 15% * [ mol/l] * [ mol/l] * 0 IL-8 0 Lactose digestion 0 Galactose absorbtion Shen et al., Am.J.Physiol. (2015)

15 Body weight (g) First nutrition after term and preterm birth - What are the long term consequenses? term preterm Minimal enteral for 5d Total parenteral for 5d Minimal enteral for 5d Total parenteral for 5d Term litter 1: MEN-BC Term litter 1: TPN Preterm litter 1: MEN-BC Preterm litter 1: TPN 500 Andersen et al., 2016 Am. J. Physiol Days of life

16 Term suckling pigs Term formula fed pigs Preterm healthy pigs Preterm NEC pigs

17 Feeding milk replacer under germ free conditions Trophic effects on the intestine in response to enteral nutrition. No pathological changes. Sangild et al Gastroenterology.

18 Department of Nutrition, Exercise and Sports Antibiotics intervention Antibiotic Dose Bacteria IA anti PO anti Control targeted Ampicillin 30 mg x kg x 3 daily 30 mg x kg x 3 daily Gram + (-) Gentamycin 2,5 mg x kg x 2 daily 2,5 mg x kg x 2 daily Gram (+), aerobes, mycoplasma Mitronidazole 10 mg x kg x 3 daily 10 mg x kg x 3 daily Anaerobes Saline 2 ml x 3 daily None Slide 18 Jensen et al. 2013, Am. J. Physiol

19 Institut for Idræt og Ernæring Reduced incidence, severity and gut permeability NEC incidence, % *** ANTI CON NEC severity, score *** ANTI CON Lactulose manitol, ratio * Antibiotics Control ANTI CON Jensen et al. 2013, Am. J. Physiol

20 Institut for Idræt og Ernæring Markedly reduced CFU and SCFA, MEANS+SEM CFU 1.00E E E E E E E E E E E+00 *** *** ANTI CON ANTI CON Aerobic Anaerobic SCFA, mmol/kg Others Octanoic acid 40 Succinic acid ** Lactic acid Butyric acid Acetic acid Formic acid ANTI CON ANTI CON Stomach Colon Jensen et al. 2013, Am. J. Physiol

21 Fecal gut microbiota in infants 12 Bifidobacteria 10 CFU in faecal contents (log10) Enterobacteria Streptococci Lactobacilli Staphylococci Clostridia Modified from Mitsuoka, 1996 AGE IN DAYS

22 Enhedens navn Fecal microbial Transfer (FMT) to preterm pigs Brunse & Martin et al. ISME (accepted) Sted og dato Slide 22

23 Enhedens navn Choise of donor? Phage therapy? NEC incidence CON: 62% (8/13) Donor 1: 38% (5/13) Donor 2: 8% (1/13) Sted og dato Slide 23

24 Comparative Pediatrics and Nutrition, Univ. Copenhagen