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Prebiotics and Bioactive Milk Fractions Affect Gut Development, Microbiota, and Neurotransmitter Expression in Piglets

Berding, Kirsten*; Wang, Mei; Monaco, Marcia H.; Alexander, Lindsey S.; Mudd, Austin T.‡,§; Chichlowski, Maciej||; Waworuntu, Rosaline V.||; Berg, Brian M.*,||; Miller, Michael J.*,†; Dilger, Ryan N.*,‡,§; Donovan, Sharon M.*,†

Journal of Pediatric Gastroenterology & Nutrition: December 2016 - Volume 63 - Issue 6 - p 688–697
doi: 10.1097/MPG.0000000000001200
Original Articles: Nutrition

Objective: This study tested the hypothesis that the addition of prebiotics and 2 functional milk ingredients to infant formula would maintain normal growth and gut development, and modify microbiota composition and neurotransmitter gene expression in neonatal piglets.

Methods: Two-day-old male piglets (n = 24) were fed formula (CONT) or formula with polydextrose (1.2 g/100 g diet), galactooligosaccharides (3.5 g/100 g diet), bovine lactoferrin (0.3 g/100 g diet), and milk fat globule membrane-10 (2.5 g/100 g diet) (TEST) for 30 days. On study day 31, intestinal samples, ileal and colonic contents, and feces were collected. Intestinal histomorphology, disaccharidase activity, serotonin (5’HT), vasoactive intestinal peptide (VIP), and tyrosine hydroxylase (TH) were measured. Gut microbiota composition was assessed by pyrosequencing of the V3–V5 regions of 16S rRNA and quantitative polymerase chain reaction.

Results: Body weight of piglets on TEST was greater (P ≤ 0.05) than CONT on days 17 to 30. Both groups displayed growth patterns within the range observed for sow-reared pigs. TEST piglets had greater jejunal lactase (P = 0.03) and higher (P = 0.003) ileal VIP expression. TEST piglets tended to have greater (P = 0.09) sucrase activity, longer (P = 0.08) ileal villi, and greater (P = 0.06) duodenal TH expression. Microbial communities of TEST piglets differed from CONT in ascending colon (AC, P = 0.001) and feces (P ≤ 0.05). CONT piglets had greater relative abundances of Mogibacterium, Collinsella, Klebsiella, Escherichia/Shigella, Eubacterium, and Roseburia compared with TEST piglets in AC. In feces, CONT piglets harbored lower (P ≤ 0.05) proportions of Parabacteroides, Clostridium IV, Lutispora, and Sutterella than TEST piglets.

Conclusions: A mixture of bioactive ingredients improved weight gain and gut maturation, modulated colonic and fecal microbial composition, and reduced the proportions of opportunistic pathogens.

*Division of Nutritional Sciences

Department of Food Science and Human Nutrition

Piglet Nutrition and Cognition Laboratory, Department of Animal Sciences

§Neuroscience Program, University of Illinois, Urbana-Champaign

||Mead Johnson Pediatric Nutrition Institute, Evansville, IN.

Address correspondence and reprint requests to Sharon M. Donovan, Department of Food Science and Human Nutrition, University of Illinois, 339 Bevier Hall, 905 South Goodwin Ave, Urbana, IL 61801 (e-mail:

Received 30 October, 2015

Accepted 11 March, 2016

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (

This study was supported by a grant from Mead Johnson Nutrition (Evansville, IN).

S.D., M.M., and R.D. have received grant funding. S.D. has served on advisory boards, and S.D., R.D., M.W., M.M., L.A., and R.D. have consulted for Mead Johnson Nutrition. M.C., R.W., and B.B. are employees of Mead Johnson Nutrition. The remaining authors report no conflicts of interest.

© 2016 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,