Necrotizing enterocolitis (NEC) is the most common serious, acquired disease of the gastrointestinal tract in preterm infants (Lee 2003). It is characterized by bowel wall necrosis of various length and depth, with perforation in one third of affected infants (Kafetzis 2003). Although 5 ‐ 25% of cases occur in term infants, it is primarily a disease of preterm infants with majority of cases occurring in Very Low Birth Weight (VLBW < 1500 gm) infants (Kosloske 1994). NEC is categorized into three different stages with clinical symptoms varying from feeding intolerance to severe cardiovascular compromise, coagulopathy, peritonitis, with or without pneumoperitoneum (Bell 1978).

The incidence of NEC varies among countries and neonatal centers. It has been reported to affect up to 10% of VLBW infants (Kosloske 1994). These infants represent some of the sickest infants in the Neonatal intensive Care Unit (NICU) and exhibit a mortality rate up to 20% of all NEC cases across the centers (Caplan 2001; Holman 1997). Approximately 27 ‐ 63% of affected infants require surgical interventions (Lee 2003). Strictures, primarily in the colon, occur in more than one third of affected infants (Ricketts 1994). Increased rate of total parenteral nutrition (TPN) related complications, and extended hospitalization has been reported (Bisquera 2002). Recent data out of the National Institute of Child Health and Human Development Network (NICHD) suggests an increase in neurodevelopmental impairment rates among infants with NEC and sepsis (Stoll 2004).

The pathogenesis of NEC remains incompletely understood, it most likely represents a complex interaction of factors causing mucosal injury and infants subsequent response (Neu 1996). It is speculated that NEC occurs with the coincidence of two of the three pathologic events; intestinal ischemia, colonization by pathologic bacteria, and excess protein substrate in the intestinal lumen (Kosloske 1984; La Gamma 1994). An animal model for NEC has demonstrated the need of bacterial colonization in the development of NEC (Kosloske 1990, Musemeche 1986). VLBW infants at risk of NEC have an aberrant fecal colonization when compared to term infants. They demonstrate a paucity of normal enteric bacterial species and delayed onset of colonization when compared to term infants (Goldmann 1978; Gewolb 1999).

Nosocomial infections are frequent complication among VLBW infants. Data of the NICHD Network demonstrated that as many as 25% of these infants have at least one or more positive blood cultures, and 5% have positive cerebrospinal fluid cultures over the course of their neonatal hospitalization (Stoll 1996). Late onset sepsis is associated with an increased risk of death, neonatal morbidities and prolonged hospitalization (Stoll 2002a; Stoll 2002b).

Probiotic bacteria are live microbial supplements that colonize the gut and provide benefit to the host (Millar 2003). The most frequently used probiotics are lactobacillus and Bifidobacterium. There is an increasing interest in the potential health benefits of proactive colonization of the gastrointestinal tract of preterm infants (Millar 2003). Potential mechanisms by which probiotics may protect high risk infants from developing NEC and/or sepsis include; increased barrier to translocation bacteria and their products across the mucosa (Orrhage 1999; Mattar 2001), competitive exclusion of potential pathogens (Reid 2001), modification of host response to microbial products (Duffy 2000), augment IGA mucosal responses, enhancing enteral nutrition that inhibit the growth of pathogens, and up‐regulation of immune responses (Link‐Amster 1994). Although data on probiotics have universally suggested safety, there is a theoretical risk of bacteremia secondary to enterally administered probiotics strains. Bacillus species administered as probiotics, were reported to be associated with invasive disease in target populations (Richard 1988).