Diet- and Colonization-Dependent Intestinal Dysfunction Predisposes to Necrotizing Enterocolitis in Preterm Pigs

Per T. Sangild, Richard H. Siggers, Mette Schmidt, Jan Elnif, Charlotte R. Bjornvad, Thomas Thymann, Marie L. Grondahl, Axel K. Hansen, Soeren K. Jensen, Mette Boye, Lars Moelbak, Randal Buddington, Björn R. Weström, Jens J. Holst, Douglas G. Burrin

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Abstract

Background & Aims: Preterm birth and formula feeding are key risk factors associated with necrotizing enterocolitis (NEC) in infants, but little is known about intestinal conditions that predispose to disease. Thus, structural, functional, and microbiologic indices were used to investigate the etiology of spontaneous NEC development in preterm pigs. Methods: Piglets were delivered by cesarean section at 92% gestation, reared in infant incubators, and fed infant formula or colostrum every 3 hours (n = 120) until tissue collection at 1-2 days of age. Results: Clinical and histopathologic signs of NEC were observed in 57% of pigs fed FORMULA (26/46) and in 5% of pigs fed COLOSTRUM (2/38) (P < .05). Relative to COLOSTRUM, both healthy and sick FORMULA pigs had reduced intestinal villous heights, enzyme activities, nutrient absorption, and antioxidant levels and higher inducible nitric oxide synthetase activity (P < .05). In healthy pigs, mucosal microbial diversity remained low and diet independent. NEC pigs showed bacterial overgrowth, and a high mucosal density of Clostridium perfringens was detected in some but not all pigs. Germ-free conditions and antiserum against Clostridium perfringens toxin prevented intestinal dysfunction and NEC in formula-fed pigs, whereas the gut trophic factors, epidermal growth factor, and glucagon-like peptide 2 had limited effects. Conclusions: A subclinical, formula-induced mucosal atrophy and dysfunction predispose to NEC and bacterial overgrowth. The adverse feeding effects are colonization dependent and may be reduced by factors in colostrum that include antibodies against aggressive toxins such as those of Clostridium perfringens.

Original languageEnglish (US)
Pages (from-to)1776-1792
Number of pages17
JournalGastroenterology
Volume130
Issue number6
DOIs
StatePublished - Jan 1 2006

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Necrotizing Enterocolitis
Swine
Diet
Clostridium perfringens
Colostrum
proctolin
Infant Incubators
Glucagon-Like Peptide 2
Infant Formula
Premature Birth
Epidermal Growth Factor
Nitric Oxide Synthase
Cesarean Section
Atrophy
Immune Sera
Antioxidants
Food
Pregnancy
Antibodies
Enzymes

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Sangild, P. T., Siggers, R. H., Schmidt, M., Elnif, J., Bjornvad, C. R., Thymann, T., ... Burrin, D. G. (2006). Diet- and Colonization-Dependent Intestinal Dysfunction Predisposes to Necrotizing Enterocolitis in Preterm Pigs. Gastroenterology, 130(6), 1776-1792. https://doi.org/10.1053/j.gastro.2006.02.026

Diet- and Colonization-Dependent Intestinal Dysfunction Predisposes to Necrotizing Enterocolitis in Preterm Pigs. / Sangild, Per T.; Siggers, Richard H.; Schmidt, Mette; Elnif, Jan; Bjornvad, Charlotte R.; Thymann, Thomas; Grondahl, Marie L.; Hansen, Axel K.; Jensen, Soeren K.; Boye, Mette; Moelbak, Lars; Buddington, Randal; Weström, Björn R.; Holst, Jens J.; Burrin, Douglas G.

In: Gastroenterology, Vol. 130, No. 6, 01.01.2006, p. 1776-1792.

Research output: Contribution to journalArticle

Sangild, PT, Siggers, RH, Schmidt, M, Elnif, J, Bjornvad, CR, Thymann, T, Grondahl, ML, Hansen, AK, Jensen, SK, Boye, M, Moelbak, L, Buddington, R, Weström, BR, Holst, JJ & Burrin, DG 2006, 'Diet- and Colonization-Dependent Intestinal Dysfunction Predisposes to Necrotizing Enterocolitis in Preterm Pigs', Gastroenterology, vol. 130, no. 6, pp. 1776-1792. https://doi.org/10.1053/j.gastro.2006.02.026
Sangild, Per T. ; Siggers, Richard H. ; Schmidt, Mette ; Elnif, Jan ; Bjornvad, Charlotte R. ; Thymann, Thomas ; Grondahl, Marie L. ; Hansen, Axel K. ; Jensen, Soeren K. ; Boye, Mette ; Moelbak, Lars ; Buddington, Randal ; Weström, Björn R. ; Holst, Jens J. ; Burrin, Douglas G. / Diet- and Colonization-Dependent Intestinal Dysfunction Predisposes to Necrotizing Enterocolitis in Preterm Pigs. In: Gastroenterology. 2006 ; Vol. 130, No. 6. pp. 1776-1792.
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T1 - Diet- and Colonization-Dependent Intestinal Dysfunction Predisposes to Necrotizing Enterocolitis in Preterm Pigs

AU - Sangild, Per T.

AU - Siggers, Richard H.

AU - Schmidt, Mette

AU - Elnif, Jan

AU - Bjornvad, Charlotte R.

AU - Thymann, Thomas

AU - Grondahl, Marie L.

AU - Hansen, Axel K.

AU - Jensen, Soeren K.

AU - Boye, Mette

AU - Moelbak, Lars

AU - Buddington, Randal

AU - Weström, Björn R.

AU - Holst, Jens J.

AU - Burrin, Douglas G.

PY - 2006/1/1

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N2 - Background & Aims: Preterm birth and formula feeding are key risk factors associated with necrotizing enterocolitis (NEC) in infants, but little is known about intestinal conditions that predispose to disease. Thus, structural, functional, and microbiologic indices were used to investigate the etiology of spontaneous NEC development in preterm pigs. Methods: Piglets were delivered by cesarean section at 92% gestation, reared in infant incubators, and fed infant formula or colostrum every 3 hours (n = 120) until tissue collection at 1-2 days of age. Results: Clinical and histopathologic signs of NEC were observed in 57% of pigs fed FORMULA (26/46) and in 5% of pigs fed COLOSTRUM (2/38) (P < .05). Relative to COLOSTRUM, both healthy and sick FORMULA pigs had reduced intestinal villous heights, enzyme activities, nutrient absorption, and antioxidant levels and higher inducible nitric oxide synthetase activity (P < .05). In healthy pigs, mucosal microbial diversity remained low and diet independent. NEC pigs showed bacterial overgrowth, and a high mucosal density of Clostridium perfringens was detected in some but not all pigs. Germ-free conditions and antiserum against Clostridium perfringens toxin prevented intestinal dysfunction and NEC in formula-fed pigs, whereas the gut trophic factors, epidermal growth factor, and glucagon-like peptide 2 had limited effects. Conclusions: A subclinical, formula-induced mucosal atrophy and dysfunction predispose to NEC and bacterial overgrowth. The adverse feeding effects are colonization dependent and may be reduced by factors in colostrum that include antibodies against aggressive toxins such as those of Clostridium perfringens.

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