Neonatal necrotizing enterocolitis, a disease of the immature intestinal mucosal barrier

Israël, E

doi:10.1111/j.1651-2227.1994.tb13238.x

Cited by 102 publications

(53 citation statements)

References 36 publications

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“…This would have far-reaching therapeutic implications. An example of such an application would be the oral use of Ig and specific antibodies in the vulnerable premature neonate to prevent necrotizing enterocolitis (26,27). A detailed understanding of the function of the FcRn in the neonatal human intestine and the various factors and cytokines that regulate its expression may have significant clinical application in the management of perinatal disease.…”

Section: Discussionmentioning

confidence: 99%

Distribution of the IgG Fc Receptor, FcRn, in the Human Fetal Intestine

Shah¹,

Dickinson²,

Blumberg³

et al. 2003

Pediatric Research

100

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The intestinal Fc receptor, FcRn, functions in the maternofetal transfer of gamma globulin (IgG) in the neonatal rodent. In humans, most of this transfer is presumed to occur in utero via the placenta. Although the fetus swallows amniotic fluid that contains immunoglobulin, it is unknown whether this transfer also occurs via the fetal intestine. A human FcRn has been identified in the syncytiotrophoblast that mediates the maternofetal transfer of antibody. It has also been identified in human fetal intestine and is postulated to function in IgG transport. We hypothesize that the human fetal intestinal FcRn may play a role in IgG transport from the amniotic fluid into the fetal circulation. The aim of this study was to characterize the distribution of the FcRn along the human fetal intestine. Lysates prepared from human fetal intestine and from a nonmalignant human fetal intestinal epithelial cell line (H4) were subjected to Western blot analysis and probed using anti-FcRn antibodies. A 42-kD band, consistent with the known molecular weight of the FcRn, was detected along the human fetal intestine and in H4 cells. Expression of the human FcRn was confirmed with immunohistochemistry. Our study demonstrates the expression of FcRn along the human fetal intestine and in a human nonmalignant fetal intestinal epithelial cell line (H4), which by location indicates that FcRn could play a role in the uptake and transport of IgG in the human fetus.Humoral immunity acquired via maternofetal transfer of antibody is critical in the prevention of perinatal infections. In rodents, this transfer occurs through the yolk sac and the intestine via a Fc receptor for IgG (FcRn). This receptor has been considered important in the maternofetal transmission of IgG in the yolk sac of mice and rats and also in the human placental syncytiotrophoblast (1). The FcRn is also expressed in the small intestine of suckling mice and rats, where the receptor functions in the uptake of IgG from ingested maternal milk. Although a FcRn has been demonstrated on the human fetal small intestine, a similar function for this receptor in the human fetal intestine has not been demonstrated to date.The acquisition of humoral immunity early in life may have a significant lifelong impact on the prevention of infectious and inflammatory diseases. Because IgG synthesis in the human fetus is reduced, most IgG in the blood of newborns is maternal in origin. Low levels of IgG

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Section: Discussionmentioning

confidence: 99%

Distribution of the IgG Fc Receptor, FcRn, in the Human Fetal Intestine

Shah¹,

Dickinson²,

Blumberg³

et al. 2003

Pediatric Research

100

View full text Add to dashboard Cite

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“…Ninety percent of NEC patients had been fed formula without human milk (52,53), and inclusion of human milk in the diet of the premature infant is associated with a lower risk of NEC. This is most often attributed to direct immunomodulation by milk, the prebiotic effect of its indigestible complex carbohydrates (glycans), the ability of glycans to inhibit colonization by pathogens, or combinations of these activities (2,31).…”

Section: Human Milkmentioning

confidence: 99%

Protection of the Neonate by the Innate Immune System of Developing Gut and of Human Milk

2007

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ABSTRACT:The neonatal adaptive immune system, relatively naïve to foreign antigens, requires synergy with the innate immune system to protect the intestine. Goblet cells provide mucins, Paneth cells produce antimicrobial peptides, and dendritic cells (DCs) present luminal antigens. Intracellular signaling by Toll-like receptors (TLRs) elicits chemokines and cytokines that modulate inflammation. Enteric neurons and lymphocytes provide paracrine and endocrine signaling. However, full protection requires human milk. Breast-feeding reduces enteric infection and may reduce chronic disease in later life. Although human milk contains significant secretory immunoglobulin A (sIgA), most of its protective factors are constitutively expressed. Multifunctional milk components are nutrients whose partial digestion products inhibit pathogens. Cytokines, cytokine receptors, TLR agonists and antagonists, hormones, antiinflammatory agents, and nucleotides in milk modulate inflammation. Human milk is rich in glycans (complex carbohydrates): As prebiotics, indigestible glycans stimulate colonization by probiotic organisms, modulating mucosal immunity and protecting against pathogens. Through structural homology to intestinal cell surface receptors, glycans inhibit pathogen binding, the essential first step of pathogenesis. Bioactive milk components comprise an innate immune system of human milk whereby the mother protects her nursing infant. Interactions between human milk glycans, intestinal microflora, and intestinal mucosa surface glycans underlie ontogeny of innate mucosal immunity, pathobiology of enteric infection, and inflammatory bowel diseases. (Pediatr Res 61: 2-8, 2007)

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“…Developmental expression of mucin genes changes throughout the intestine and matches adult pattern expression between 23 and 27 wk gestation [37] . Microvilli of immature intestine also have altered glycosylation patterns [38] . Since carbohydrate sequences are recognition and attachment sites for microbes, changes in glycosylation patterns may influence the bacterial colonization pattern of the gut.…”

Section: Immature Intestinal Motility Digestion and Barrier Functionmentioning

confidence: 99%

Necrotizing enterocolitis: A multifactorial disease with no cure

Schnabl

Aerde²,

Thomson³

et al. 2008

WJG

163

120

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INTRODUCTIONNecrotizing enterocolitis (NEC) is an inflammatory bowel disease of neonates and remains one of the most common gastrointestinal emergencies in newborn infants [1] . Onset of NEC is often within the first three months of life and neonates who are of extremely low birth weight (< 1000 g) and under 28 wk gestation are the most susceptible [2] . Full term neonates account for 10% of all NEC cases while premature infants account for 90% [3] . With an incidence rate of 1%-5% for all newborns admitted to the NICU [1] , a prevalence of 7%-14% of very low birth weight infants (VLBW, 500-1500 g) [4] and a mortality rate approaching 20%-50% [5] , NEC continues to represent a significant clinical problem. In Canada, the incidence rate is 1.8 per 100 live births with a prevalence of 7% of VLBW infants [1] . Advances in obstetric and neonatal care have improved survival rates for smaller, more immature infants, and as more VLBW preterm infants survive the neonatal period, the population at risk for NEC increases [1] .No consistent association between sex, race, and rates of NEC has been identified. However, male VLBW infants and black infants are at greater risk of death [6] . Due to inadequate treatments and no effective preventative strategy, an estimated 20%-40% of babies with NEC require surgery [1] and 10%-30% experience significant morbidity including neurodevelopmental impairment, vision and hearing impairment, failure to thrive, feeding abnormalities, diarrhea, bowel obstruction, and short bowel syndrome [1,2,7] . The case fatality rate with surgical intervention is as high as 50% [1] . NEC is also a financial burden to the health care system with yearly hospital charges reported to be as high as $6.5 million in the US [8] . Thus, NEC continues to be an important health issue for preterm neonates. DIAGNOSIS Clinical signs and symptomsThe onset of NEC can occur suddenly within a few AbstractNecrotizing enterocolitis is an inflammatory bowel disease of neonates with significant morbidity and mortality in preterm infants. Due to the multifactorial nature of the disease and limitations in disease models, early diagnosis remains challenging and the pathogenesis elusive. Although preterm birth, hypoxic-ischemic events, formula feeding, and abnormal bacteria colonization are established risk factors, the role of genetics and vasoactive/inflammatory mediators is unclear. Consequently, treatments do not target the specific underlying disease processes and are symptomatic and surgically invasive. Breast-feeding is the most effective preventative measure. Recent advances in the prevention of necrotizing enterocolitis have focused on bioactive nutrients and trophic factors in human milk. Development of new disease models including the aspect of prematurity that consistently predisposes neonates to the disease with multiple risk factors will improve our understanding of the pathogenesis and lead to discovery of innovative therapeutics.

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Neonatal necrotizing enterocolitis, a disease of the immature intestinal mucosal barrier

Cited by 102 publications

References 36 publications

Distribution of the IgG Fc Receptor, FcRn, in the Human Fetal Intestine

Distribution of the IgG Fc Receptor, FcRn, in the Human Fetal Intestine

Protection of the Neonate by the Innate Immune System of Developing Gut and of Human Milk

Necrotizing enterocolitis: A multifactorial disease with no cure

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