Probiotics: Role in Pathophysiology and Prevention in Necrotizing Enterocolitis

https://doi.org/10.1053/j.semperi.2008.01.006Get rights and content

Necrotizing enterocolitis (NEC) is an inflammatory bowel disease largely affecting low birth weight, premature infants. Once acquired, NEC is accompanied by significant mortality and morbid sequelae. Our understanding of the pathophysiology of NEC continues to evolve, and the development of NEC is likely multifactorial with resultant bowel injury mediated through a final, common inflammatory pathway. The predisposition for NEC appears to involve the interplay between intestinal integrity and function, enteral feeding and bacterial colonization, and regulation of the gastrointestinal and systemic inflammatory response. Commensal organisms or probiotics have been shown to be crucial in the development and modulation of each of these factors within the intestinal epithelium. As a result, probiotic supplementation has been proposed as a promising new intervention for the prevention of NEC. To understand the potential utility of probiotics in NEC, we will discuss: the components of gut defense; the role of the intestinal ecosystem in modulating immunity and inflammation; bacterial colonization patterns in the preterm infant compared with patterns seen in the healthy, full-term infant; the evidence for probiotic use in other populations and diseases; and finally, the evidence of probiotic use specific to the preterm infant and NEC.

Section snippets

Components of the Gut Defense

The fully developed gastrointestinal system possess local nonspecific barrier defenses and cell-specific antigen interactions that function together to protect the gut from colonization and translocation of potentially pathogenic bacteria and antigens.13 The local defenses include gastric acidity and digestive enzymes to destroy ingested pathogens and associated antigens, mucus production to inhibit microbial adherence, active regular peristalsis to prevent bacterial stasis and rapidly

Bacterial Colonization of the Developing Gut

In utero the fetal gut is bathed in sterile amniotic fluid enriched with nutrients, hormones, and growth factors which aid in the development of the intestinal tract.41 At delivery, the newborn leaves this sterile environment and is exposed to environmental organisms, some of which establish residence and colonize the gut. Colonization by nonpathogenic, commensal organisms creates a stable and diverse intestinal flora which is essential for the ongoing development of both intestinal structure

Probiotics and Health

Although the use of probiotics (“for life”) for health benefit has received a fair amount of attention in the past decade, the potential health benefits of nonpathogenic microorganisms have been described centuries ago in the Old Testament and classical Roman literature.69, 70 The term probiotic was first introduced in 1965 and the definition has since undergone many variations.71 In 2001, the Food and Agriculture Organization (FAO) of the United Nations and the World Health Organization (WHO)

Rationale

NEC, an inflammatory bowel disease largely specific to the preterm infant, is characterized by the disruption of intestinal mucosal integrity leading to an acute clinical presentation of feeding intolerance, bloody stools, and pneumointestinalis, and is accompanied by a systemic inflammatory response of cardiorespiratory compromise and severe hemodynamic instability. As reviewed, the preterm infant is especially vulnerable to the development of NEC as a result of inappropriate intestinal

Conclusion

Ongoing development of the gastrointestinal system continues after birth and relies on the establishment of a stable and diverse intestinal microbial population. This symbiotic relationship between commensal organisms and the host enhances the maturity of the intestinal defenses and modulates the inmate immune system and gut inflammation.

The developmental immaturity of the preterm gut and the exposure to the NICU environment and associated treatments promotes inappropriate intestinal

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