microbes, diet and host: how do they interact in newborn ...... variation in maturity at birth ?...

Department of Veterinary Clinical and Animal Sciences

Microbes, diet and host: how do they interact in newborn piglets ?

Thomas Thymann, MSc, DVM, PhD, Assoc. Prof Comparative Pediatrics and Nutrition Faculty of Health and Medical Sciences University of Copenhagen

www.Neomune.ku.dk

Variation in maturity at birth ?

115d

115d

116d

114d

118d

116d

113d

115d

Large litters

Optimal timing:

Preterm Pig Intensive Care Unit - to help answer difficult questions!

25 incubators Respiratory support Temp./moisture control Low microbe (germfree) Parenteral/enteral nutrition 24 hour camera surveillance

Nutrition

Immunity Microbiota

Preterm gut

Preterm pig Colostrum Preterm pig - Formula

NEC

Main risk factors of necrotizing enterocolitis (NEC): Prematurity, formula nutrition and gut colonization

Sangild et al. 2006. Gastroenterology.

Trophic effects on the intestine in response to enteral nutrition. No pathological changes.

Feeding milk replacer under germ free conditions

Treatment groups

Department of Nutrition, Exercise and Sports Slide

10

Antibiotic Dose Bacteria

targeted IA anti PO anti Control

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

Jensen et al. 2013, Am. J. Physiol

0

20

40

60

80

100

1

2

3

4

5

6

ANTI CON ANTI CON 0,0

0,1

0,2

0,3

0,4

Antibiotics Control ANTI CON La

ctul

ose-

man

itol,

ratio

*

***

NEC

seve

rity,

scor

e

NEC

inci

denc

e, %

Reduced incidence, severity

and gut permeability

***

Institut for Idræt og Ernæring

Jensen et al. 2013, Am. J. Physiol

Markedly reduced CFU and SCFA, MEANS+SEM

*** ***

1,00E+00

1,00E+01

1,00E+02

1,00E+03

1,00E+04

1,00E+05

1,00E+06

1,00E+07

1,00E+08

1,00E+09

1,00E+101010

108

106

104

102

0

ANTI CON

Aerobic Anaerobic

ANTI CON

0.07

** 0

10

20

30

40

50

60

70

ANTI CON ANTI CON

Stomach Colon

Others

Octanoic acid

Succinic acid

Lactic acid

Butyric acid

Acetic acid

Formic acid

CFU

SCFA

, mm

ol/k

g

ANTI CON ANTI CON

Institut for Idræt og Ernæring

Jensen et al. 2013, Am. J. Physiol

C D

Gao, Nguyen, Birck et al.

mm

ol g

luco

se/k

g*h

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

LACTOSEMALTODEXTRIN

time, min

-80 -60 -40 -20 0 20 40 60 80 100 120 140

mm

ol g

alac

tose

/kg*

h

-0.4

-0.2

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

glucose

galactose

Direct infusion of lactose or MDX in the jejunum (Burrin & Stoll)

NEC incidence

3/11 10/11

27%

91%

0

10

20

30

40

50

60

70

80

90

100

LACTOSE POLYCOSE

P<0.001

Lactose Maltodextrin

Thymann et al. Am. J. Physiol., 2009

Slow progression of enteral feeds in preterm pigs

Shen et al., Am. J. Physiol. (2015)

Gut responses TPN Infant Formula Bovine Colostrum(n=6-14) (IF, n=8-15) (BC, n=7-13)

0

50

100

150

*

IL-8

0.00

0.05

0.10

0.15

0.20

*

Gut permeablityLa

c/M

an-r

atio

0

500

1000

1500

*

Galactose absorbtion

[µm

ol/L

]

0

100

200

300

400

*

Lactose digestion

[µm

ol/L

]0%

60%

15%

***

NEC 0

20

40

60

80

100

15%

93%

7%

**

Diarrhea

% o

f an

imal

s

Am.J.Physiol. (2015)

0 5 10 15 20 25500

1000

1500

2000

2500

3000

3500

4000

Term litter 1: MEN-BCTerm litter 1: TPNPreterm litter 1: MEN-BC Preterm litter 1: TPN

Body weight (g)

Days of life

First nutrition after term and preterm birth - What are the long term consequenses ?

Minimal enteral for 5d Total parenteral for 5d Minimal enteral for 5d Total parenteral for 5d

term preterm

PCoA on day 26

Enhedens navn Dias

19

PhD Status Seminar 4 March 2016

Milk and Microbiota Effects on Immunity, Gut, Liver and Brain in Preterm Infants

Comparative Pediatrics and Nutrition, Univ. Copenhagen

18/10/2016 22