Disturbance of normal gastrointestinal ontogenesis, early postnatal stress, different pattern of gastrointestinal colonization, changes in the microbiota induced by infection or early use of antibiotics in Neonatal Intensive Care Unit (NICU), or other events, perturb physiologic inflammation and gut physiology, resulting in an aberrant activation of intestinal peristalsis and gut-brain axis [
39]. Aberrant intestinal functions development are the major determinant for feeding intolerance (FI), a major problem in NICU. FI is defined as the inability to digest enteral feedings and may be considered as a predictive value for a developing NEC [
40]. FI occurs most commonly in very low birth weight (VLBW) infants, indicating a deficiency in the developmental pattern of gastrointestinal tract with decreasing gestational age (GA). Newborns require structural and functional maturation of gastrointestinal tract for the digestion and absorption of the nutrient elements from colostrum and breast milk. A complete intestinal motor function development includes suck - swallow coordination, gastroesophageal sphincter tone continence, adequate gastric emptying and intestinal peristalsis. Term newborns are able to acquire adequate quantities of nutrients to promote the rapid growth that occurs shortly after birth. However, half of preterm infants are delayed in achieving full enteral feeding volumes and present reflux, gastric residual and constipation due to delayed gastric emptying, prolonged intestinal transit, abdominal distension, and delayed passage of meconium, all of which reflex gastrointestinal functions immaturity [
41]. There are few studies available about the fetal ontogenesis and the neonatal early adaptation of motility and mucosal barrier functions of the human gut [
42‐
44]. Functional components of the human gastrointestinal tract do not evolve simultaneously: in facts, althought anatomical differentiation of human gut is usually achieved within 20 weeks of gestation, the functional maturation is postponed over time and require an organized peristalsis and a coordinated sucking and swallowing reflexes, that are not extabished, respectively, until 29–30 weeks and 32–34 weeks of gestations [
45]. As illustrated before, the early composition of the intestinal microbiota at birth can influence the correct ontogenesis of gut barrier, motor and immune functions through a complex neuroendocrine cross-talk [
46]. Thus, an appropriate colonization of the gastrointestinal tract after birthis likely to play an important role in the final development of gut functions. Premature infants have an abnormal colonization, tend to colonize with fewer bacteria, are routinely administered antibiotics, are often born via caesarian section, and are exposed to highly pathogenic institutional organisms [
47,
48]. Examining the intestinal bacteria present in premature infants may be an important determinant in the pathogenesis of feeding intolerance and necrotizing enterocolitis (NEC) [
49]. Using advanced technologies and stool samples studies have shown that infants who develop NEC have significantly less bacterial diversity in their intestinal microbiota with presence of certain pathogenic bacteria and the lack of protective bacteria [
50,
51].
Exposure to “non-beneficial” microorganisms and antibiotics early in life may result in immune dysregulation, aberrant barrier functions, and alterated gut sensorimotor functions that, in susceptible individuals, may lead to some disease states after birth or later in life. Efforts to optimize the intestinal microbiota colonization at birth in neonates who are born by caesarean delivery, born preterm, exposed to antibiotics and/or fed with infant-sterile-formulas, have increased the interest in early probiotics supplementation. Introducing probiotic to preterm infants has been postulated to enhance enteral feeding, prevent NEC and avoid overgrowth of pathogenic organism. Probiotics are live microbes that provide health benefits to the host when dispensed in adequate doses. Many strains that are part of the human intestinal microbiota could be considered as potential probiotics but microorganisms used in prevention and treatment of pediatric clinical diseases are typically members of the genera lactobacillus and bifidobacterium, following the natural evolution of the microbial colonization in a healty term breast-fed baby.