microbes, diet and host: how do they interact in newborn ...... variation in maturity at birth ?...
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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
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www.Neomune.ku.dk
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Variation in maturity at birth ?
115d
115d
116d
114d
118d
116d
113d
115d
Large litters
Optimal timing:
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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
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Nutrition
Immunity Microbiota
Preterm gut
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Preterm pig Colostrum Preterm pig - Formula
NEC
Main risk factors of necrotizing enterocolitis (NEC): Prematurity, formula nutrition and gut colonization
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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
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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
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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
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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
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C D
Gao, Nguyen, Birck et al.
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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)
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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
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Slow progression of enteral feeds in preterm pigs
Shen et al., Am. J. Physiol. (2015)
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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)
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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
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PCoA on day 26
Enhedens navn Dias
19
PhD Status Seminar 4 March 2016
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Milk and Microbiota Effects on Immunity, Gut, Liver and Brain in Preterm Infants
Comparative Pediatrics and Nutrition, Univ. Copenhagen
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18/10/2016 22
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