The effect of neutral oligosaccharides on fecal microbiota in premature infants fed exclusively with breast milk: A randomized clinical trial

OBJECTIVE: This study was designed to compare the efficacy and safety of enteral supplementation of a prebiotic mixture ((SC)GOS/(LC)FOS) on faecal microbiota in very premature infants who fed exclusively with human-milk. METHODS: This double-center randomized control trial was conducted from December 2012 to November 2013 in the tertiary Neonatal Intensive Care Units of the Isfahan University of Medical Sciences. Fifty preterm infants (birth weight ≤1500 g who were not fed with formula) were randomly allocated to have enteral (tube feeding) supplementation with a prebiotic mixture ((SC)GOS/(LC)FOS; 9:1) or receive no prebiotics. FINDINGS: The primary outcome (e.g., the effect of the prebiotic mixture on fecal microbiota pattern) was clearly different between the two groups. Despite greater coliforms colony counts in first stool cultures in the prebiotic group (Group P) (P = 0.67), coliforms were significantly lower in the third stool cultures in the Group P (P < 0.001). Furthermore, despite the much higher Lactobacillus colony counts, in the first stool cultures, in the control group (Group C) (P = 0.005); there was a trend toward significantly increased Lactobacillus colony counts in the Group P during the study, but the difference between Lactobacillus colony counts, in the third stool cultures, between two groups was no longer statistically significant (P = 0.11). Interestingly, the median length of hospital stay was significantly less in the Group P (16 [12.50–23.50] vs. 25 [19.50–33.00] days; P = 0.003). CONCLUSION: This suggests that it might have been “the complete removal of formula” which manifests a synergistic effect between nonhuman neutral oligosaccharides (prebiotics) and human oligosaccharides, which in turn, led to the rapid growth of beneficial Lactobacillus colonies in the gut of breast milk-fed preterm infants, while decreasing the number of pathogenic coliforms microorganisms. Therefore, further studies with larger sample sizes are recommended to investigate the issue.