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Prebiotic Oligosaccharides in Premature Infants

Underwood, Mark A.*; Kalanetra, Karen M.; Bokulich, Nicholas A.; Mirmiran, Majid*; Barile, Daniela; Tancredi, Daniel J.*; German, J. Bruce; Lebrilla, Carlito B.§; Mills, David A.

Journal of Pediatric Gastroenterology and Nutrition: March 2014 - Volume 58 - Issue 3 - p 352–360
doi: 10.1097/MPG.0000000000000211
Original Articles: Hepatology and Nutrition

Objective: The aim of the study was to determine the impact of increasing doses of 2 prebiotic oligosaccharides and of an “all-human diet” on the intestinal microbiota of premature infants.

Methods: Twelve premature infants receiving formula feedings were randomly assigned to receive either galacto-oligosaccharide (F+GOS) or a pooled concentrated donor human milk product containing human milk oligosaccharides (F+HMO) in increasing doses during a 5-week period. A second group of 15 premature infants received their mother's own milk fortified with either a concentrated donor human milk product (H+H) or a bovine powdered fortifier (H+B). Serial stool specimens from each infant were analyzed by terminal restriction fragment length polymorphism and quantitative polymerase chain reaction for bacterial composition.

Results: All of the infants studied had relatively low levels of bifidobacteria and no measurable Lactobacilli. Infants from the F+GOS and F+HMO groups demonstrated an increase in relative numbers of Clostridia with increasing doses. Compared with the H+B group, the infants in the F+HMO and the H+H groups showed an unexpected trend toward an increase in γ-Proteobacteria over time/dose. Principal coordinate analyses and Shannon diversity scores were not significantly different among the 4 groups. Infants in the H+H group received more antibiotics during the study period than those in the other groups. Two of the infants receiving GOS developed feeding intolerance.

Conclusions: None of the prebiotic interventions resulted in significant increases in bifidobacteria compared with baseline specimens or the H+B group; however, many of the infants did not receive the highest doses of GOS and HMO, and antibiotic use in the H+H group was high.

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*Department of Pediatrics

Department of Viticulture and Enology

Department of Food Science and Technology

§Department of Chemistry, University of California, Davis.

Address correspondence and reprint requests to Mark A. Underwood, Ticon 2 Room 237, 2516 Stockton Blvd, Sacramento, CA 95817 (e-mail:

Received 6 May, 2013

Accepted 9 October, 2013

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This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Development, the National Institute of Allergies and Infectious Diseases, and the National Institute of Diabetes and Digestive and Kidney Diseases (R01-HD059127). The project described was also supported by the National Center for Advancing Translational Sciences and the National Institutes of Health, through grant #UL1 TR000002. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. registration no.: NCT00810160.

The authors report no conflicts of interest.

© 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,