Postnatal amniotic fluid intake reduces gut inflammatory responses and necrotizing enterocolitis in preterm neonates

Jayda Siggers, Mette V. Østergaard, Richard H. Siggers, Kerstin Skovgaard, Lars Mølbak, Thomas Thymann, Mette Schmidt, Hanne Kristine Møller, Stig Purup, Lisbeth Nielsen Fink, Hanne Frøkiær, Mette Boye, Per T. Sangild, Stine B. Bering

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Preterm neonates are susceptible to gastrointestinal disorders such as necrotizing enterocolitis (NEC). Maternal milk and colostrum protects against NEC via growth promoting, immunomodulatory, and antimicrobial factors. The fetal enteral diet amniotic fluid (AF), contains similar components, and we hypothesized that postnatal AF administration reduces inflammatory responses and NEC in preterm neonates. Preterm pigs (92% gestation) were delivered by caesarean section and fed parental nutrition (2 days) followed by enteral (2 days) porcine colostrum (COLOS, n = 7), infant formula (FORM, n = 13), or AF supplied before and after introduction of formula (AF, n = 10) in experiment 1, and supplied only during the enteral feeding period in experiment 2 (FORM, n = 16; AF, n = 14). The NEC score was reduced in both AF and COLOS pigs, relative to FORM, when AF was provided prior to full enteral feeding (9.9 and 7.7 compared with 17.3, P <0.05). There was no effect of AF when provided only during enteral feeding. AF pigs showed decreased bacterial abundance in colon and intestinal inflammation-related genes (e.g., TNF-α, IL-1α, IL-6, NOS) were downregulated, relative to FORM pigs with NEC. Anti-inflammatory properties of AF were supported by delayed maturation and decreased TNF-α production in murine dendritic cells, as well as increased proliferation and migration, and downregulation of IL-6 expression in intestinal cells (IEC-6, IPEC-J2). Like colostrum, AF may reduce NEC development in preterm neonates by suppressing the proinflammatory responses to enteral formula feeding and gut colonization when provided before the onset of NEC.
Original languageEnglish
JournalAmerican Journal of Physiology: Gastrointestinal and Liver Physiology
Volume304
Issue number10
Pages (from-to)G864-G875
ISSN0193-1857
DOIs
Publication statusPublished - 2013

Cite this

Siggers, Jayda ; Østergaard, Mette V. ; Siggers, Richard H. ; Skovgaard, Kerstin ; Mølbak, Lars ; Thymann, Thomas ; Schmidt, Mette ; Møller, Hanne Kristine ; Purup, Stig ; Fink, Lisbeth Nielsen ; Frøkiær, Hanne ; Boye, Mette ; Sangild, Per T. ; Bering, Stine B. / Postnatal amniotic fluid intake reduces gut inflammatory responses and necrotizing enterocolitis in preterm neonates. In: American Journal of Physiology: Gastrointestinal and Liver Physiology. 2013 ; Vol. 304, No. 10. pp. G864-G875.
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title = "Postnatal amniotic fluid intake reduces gut inflammatory responses and necrotizing enterocolitis in preterm neonates",
abstract = "Preterm neonates are susceptible to gastrointestinal disorders such as necrotizing enterocolitis (NEC). Maternal milk and colostrum protects against NEC via growth promoting, immunomodulatory, and antimicrobial factors. The fetal enteral diet amniotic fluid (AF), contains similar components, and we hypothesized that postnatal AF administration reduces inflammatory responses and NEC in preterm neonates. Preterm pigs (92{\%} gestation) were delivered by caesarean section and fed parental nutrition (2 days) followed by enteral (2 days) porcine colostrum (COLOS, n = 7), infant formula (FORM, n = 13), or AF supplied before and after introduction of formula (AF, n = 10) in experiment 1, and supplied only during the enteral feeding period in experiment 2 (FORM, n = 16; AF, n = 14). The NEC score was reduced in both AF and COLOS pigs, relative to FORM, when AF was provided prior to full enteral feeding (9.9 and 7.7 compared with 17.3, P <0.05). There was no effect of AF when provided only during enteral feeding. AF pigs showed decreased bacterial abundance in colon and intestinal inflammation-related genes (e.g., TNF-α, IL-1α, IL-6, NOS) were downregulated, relative to FORM pigs with NEC. Anti-inflammatory properties of AF were supported by delayed maturation and decreased TNF-α production in murine dendritic cells, as well as increased proliferation and migration, and downregulation of IL-6 expression in intestinal cells (IEC-6, IPEC-J2). Like colostrum, AF may reduce NEC development in preterm neonates by suppressing the proinflammatory responses to enteral formula feeding and gut colonization when provided before the onset of NEC.",
author = "Jayda Siggers and {\O}stergaard, {Mette V.} and Siggers, {Richard H.} and Kerstin Skovgaard and Lars M{\o}lbak and Thomas Thymann and Mette Schmidt and M{\o}ller, {Hanne Kristine} and Stig Purup and Fink, {Lisbeth Nielsen} and Hanne Fr{\o}ki{\ae}r and Mette Boye and Sangild, {Per T.} and Bering, {Stine B.}",
year = "2013",
doi = "10.1152/ajpgi.00278.2012",
language = "English",
volume = "304",
pages = "G864--G875",
journal = "American Journal of Physiology: Gastrointestinal and Liver Physiology",
issn = "0193-1857",
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Siggers, J, Østergaard, MV, Siggers, RH, Skovgaard, K, Mølbak, L, Thymann, T, Schmidt, M, Møller, HK, Purup, S, Fink, LN, Frøkiær, H, Boye, M, Sangild, PT & Bering, SB 2013, 'Postnatal amniotic fluid intake reduces gut inflammatory responses and necrotizing enterocolitis in preterm neonates', American Journal of Physiology: Gastrointestinal and Liver Physiology, vol. 304, no. 10, pp. G864-G875. https://doi.org/10.1152/ajpgi.00278.2012

Postnatal amniotic fluid intake reduces gut inflammatory responses and necrotizing enterocolitis in preterm neonates. / Siggers, Jayda; Østergaard, Mette V.; Siggers, Richard H.; Skovgaard, Kerstin; Mølbak, Lars; Thymann, Thomas; Schmidt, Mette; Møller, Hanne Kristine; Purup, Stig; Fink, Lisbeth Nielsen; Frøkiær, Hanne; Boye, Mette; Sangild, Per T.; Bering, Stine B.

In: American Journal of Physiology: Gastrointestinal and Liver Physiology, Vol. 304, No. 10, 2013, p. G864-G875.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Postnatal amniotic fluid intake reduces gut inflammatory responses and necrotizing enterocolitis in preterm neonates

AU - Siggers, Jayda

AU - Østergaard, Mette V.

AU - Siggers, Richard H.

AU - Skovgaard, Kerstin

AU - Mølbak, Lars

AU - Thymann, Thomas

AU - Schmidt, Mette

AU - Møller, Hanne Kristine

AU - Purup, Stig

AU - Fink, Lisbeth Nielsen

AU - Frøkiær, Hanne

AU - Boye, Mette

AU - Sangild, Per T.

AU - Bering, Stine B.

PY - 2013

Y1 - 2013

N2 - Preterm neonates are susceptible to gastrointestinal disorders such as necrotizing enterocolitis (NEC). Maternal milk and colostrum protects against NEC via growth promoting, immunomodulatory, and antimicrobial factors. The fetal enteral diet amniotic fluid (AF), contains similar components, and we hypothesized that postnatal AF administration reduces inflammatory responses and NEC in preterm neonates. Preterm pigs (92% gestation) were delivered by caesarean section and fed parental nutrition (2 days) followed by enteral (2 days) porcine colostrum (COLOS, n = 7), infant formula (FORM, n = 13), or AF supplied before and after introduction of formula (AF, n = 10) in experiment 1, and supplied only during the enteral feeding period in experiment 2 (FORM, n = 16; AF, n = 14). The NEC score was reduced in both AF and COLOS pigs, relative to FORM, when AF was provided prior to full enteral feeding (9.9 and 7.7 compared with 17.3, P <0.05). There was no effect of AF when provided only during enteral feeding. AF pigs showed decreased bacterial abundance in colon and intestinal inflammation-related genes (e.g., TNF-α, IL-1α, IL-6, NOS) were downregulated, relative to FORM pigs with NEC. Anti-inflammatory properties of AF were supported by delayed maturation and decreased TNF-α production in murine dendritic cells, as well as increased proliferation and migration, and downregulation of IL-6 expression in intestinal cells (IEC-6, IPEC-J2). Like colostrum, AF may reduce NEC development in preterm neonates by suppressing the proinflammatory responses to enteral formula feeding and gut colonization when provided before the onset of NEC.

AB - Preterm neonates are susceptible to gastrointestinal disorders such as necrotizing enterocolitis (NEC). Maternal milk and colostrum protects against NEC via growth promoting, immunomodulatory, and antimicrobial factors. The fetal enteral diet amniotic fluid (AF), contains similar components, and we hypothesized that postnatal AF administration reduces inflammatory responses and NEC in preterm neonates. Preterm pigs (92% gestation) were delivered by caesarean section and fed parental nutrition (2 days) followed by enteral (2 days) porcine colostrum (COLOS, n = 7), infant formula (FORM, n = 13), or AF supplied before and after introduction of formula (AF, n = 10) in experiment 1, and supplied only during the enteral feeding period in experiment 2 (FORM, n = 16; AF, n = 14). The NEC score was reduced in both AF and COLOS pigs, relative to FORM, when AF was provided prior to full enteral feeding (9.9 and 7.7 compared with 17.3, P <0.05). There was no effect of AF when provided only during enteral feeding. AF pigs showed decreased bacterial abundance in colon and intestinal inflammation-related genes (e.g., TNF-α, IL-1α, IL-6, NOS) were downregulated, relative to FORM pigs with NEC. Anti-inflammatory properties of AF were supported by delayed maturation and decreased TNF-α production in murine dendritic cells, as well as increased proliferation and migration, and downregulation of IL-6 expression in intestinal cells (IEC-6, IPEC-J2). Like colostrum, AF may reduce NEC development in preterm neonates by suppressing the proinflammatory responses to enteral formula feeding and gut colonization when provided before the onset of NEC.

U2 - 10.1152/ajpgi.00278.2012

DO - 10.1152/ajpgi.00278.2012

M3 - Journal article

VL - 304

SP - G864-G875

JO - American Journal of Physiology: Gastrointestinal and Liver Physiology

JF - American Journal of Physiology: Gastrointestinal and Liver Physiology

SN - 0193-1857

IS - 10

ER -