Background. In a large-scale study of feeding strategies in premature infants (early vs later initiation of enteral feeding, continuous vs bolus tube-feeding, and human milk vs formula), the feeding of human milk had more effect on the outcomes measured than any other strategy studied. Therefore, this report describes the growth, nutritional status, feeding tolerance, and health of participating premature infants who were fed fortified human milk (FHM) in comparison with those who were fed exclusively preterm formula (PF). Methods. Premature infants were assigned randomly in a balanced two-way design to early (gastrointestinal priming for 10 days) versus late initiation of feeding (total parenteral nutrition only) and continuous infusion versus intermittent bolus tube-feeding groups. The type of milk was determined by parental choice and infants to receive their mother9s milk were randomized separately from those to receive formula. The duration of the study spanned the entire hospitalization of the infant. To evaluate human milk versus formula feeding, we compared outcomes of infants fed >50 mL · kg⁻¹ · day⁻¹ of any human milk (averaged throughout the hospitalization) with those of infants fed exclusively PF. Growth, feeding tolerance, and health status were measured daily. Serum indices of nutritional status were measured serially, and 72-hour nutrient balance studies were conducted at 6 and 9 weeks postnatally. Results. A total of 108 infants were fed either >50 mL · kg⁻¹ · day⁻¹ human milk (FHM,n = 62) or exclusively PF (n = 46). Gestational age (28 ± 1 weeks each), birth weight (1.07 ± 0.17 vs 1.04 ± 0.19 kg), birth length and head circumference, and distribution among feeding strategies were similar between groups. Infants fed FHM were discharged earlier (73 ± 19 vs 88 ± 47 days) despite significantly slower rates of weight gain (22 ± 7 vs 26 ± 6 g · kg⁻¹ · day⁻¹), length increment (0.8 ± 0.3 vs 1.0 ± 0.3 cm · week⁻¹), and increment in the sum of five skinfold measurements (0.86 ± 0.40 vs 1.23 ± 0.42 mm · week⁻¹) than infants fed PF. The incidence of necrotizing enterocolitis and late-onset sepsis was less in the FHM group. Overall, there were no differences in any measure of feeding tolerance between groups. Milk intakes of infants fed FHM were significantly greater than those fed PF (180 ± 13 vs 157 ± 10 mL · kg⁻¹ · day⁻¹). The intakes of nitrogen and copper were higher and magnesium and zinc were lower in group FHM versus PF. Fat and energy absorption were lower and phosphorus, zinc, and copper absorption were higher in group FHM versus PF. The postnatal retention (balance) surpassed the intrauterine accretion rate of nitrogen, phosphorus, magnesium, zinc, and copper in the FHM group, and of nitrogen, magnesium, and copper in the PF group. Conclusions. Although the study does not allow a comparison of FHM with unfortified human milk, the data suggest that the unique properties of human milk promote an improved host defense and gastrointestinal function compared with the feeding of formula. The benefits of improved health (less sepsis and necrotizing enterocolitis) associated with the feeding of FHM outweighed the slower rate of growth observed, suggesting that the feeding of FHM should be promoted actively in premature infants.

The brain-gut axis allows bidirectional communication between the central nervous system (CNS) and the enteric nervous system (ENS), linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent experimental work suggests that the gut microbiota have an impact on the brain-gut axis. A group of experts convened by the International Scientific Association for Probiotics and Prebiotics (ISAPP) discussed the role of gut bacteria on brain functions and the implications for probiotic and prebiotic science. The experts reviewed and discussed current available data on the role of gut microbiota on epithelial cell function, gastrointestinal motility, visceral sensitivity, perception and behavior. Data, mostly gathered from animal studies, suggest interactions of gut microbiota not only with the enteric nervous system but also with the central nervous system via neural, neuroendocrine, neuroimmune and humoral links. Microbial colonization impacts mammalian brain development in early life and subsequent adult behavior. These findings provide novel insights for improved understanding of the potential role of gut microbial communities on psychological disorders, most particularly in the field of psychological comorbidities associated with functional bowel disorders like irritable bowel syndrome (IBS) and should present new opportunity for interventions with pro- and prebiotics.