1. What are the differences in gut physiology between formula and breastfed infants? Does the addition of prebiotics and probiotics in formula mimic the effects of breast milk? Sahira Copenhaver Nutrition 490W Dr. Patterson Spring 2011 April 22, 2011

2. Outline Definitions Intestinal microflora of breastfed vs. formula fed infants Studies evaluating formulas with prebiotics and probiotics – Pre-term Westerbeek et al (2010) – Term Rinne et al (2005) Bakker-Zierikzee et al (2005) Where is research heading? Dietitian’s role Conclusions

3. Definitions Human Milk Oligosaccharides (HMOs) Functional Food Components – Probiotics Bifidobacteria and lactobacilli – Prebiotics Galacto-oligosaccharides (GOS) Fructo-oligosaccharides (FOS) Thomas et al Pediatrics 2010;126:1217-1231. 1

4. Intestinal Microflora of Breastfed vs. Formula Fed Infants Breastfed – Dominated by populations of Bifidobacteria Formula fed – More complex microflora with Bifidobacteria, facultative anaerobes, bacteroides, and clostridia Mountzouris et al British Journal of Nutrition 2002;87:405-420. 2

5. Enteral Supplementation of Prebiotic Mixture on Intestinal Permeability in Preterm Infants Subjects – 113 infants, gestational age <32 weeks and/or birth weight <1500g Methods – Randomly allocated Prebiotic mixture of 80% GOS/FOS + 20% AOS Placebo mixture (maltodextrin) – Intestinal Permeability Westerbeek et al British Journal of Nutrition 2011;105:268-274. 3

6. 4 0 1 2 Time point Westerbeek et al British Journal of Nutrition 2011;105:268-274. L/M Ratio 0.5 0.4 0.3 0.2 0.1 0.0 No Effect on L/M Ratio in Both Groups

7. Enteral Supplementation of Prebiotic Mixture not Correlated with Intestinal Permeability in Preterm Infants Results – Baseline patient and nutritional characteristics were not different between groups – LBW increased the L/M ratio Limitations – Timing Westerbeek et al British Journal of Nutrition 2011;105:268-274. 5

8. Similar Bifidogenic Effects on Infant Gut Microflora Subjects – 32 infants, born between 36 and 42 weeks of gestation Study Design (Four Groups) – Formula (n=8)* – Pre + Formula – Breast milk – Pro + Breast milk Rinne et al FEMS 2005;43:59-65. 6

9. Similar Bifidogenic Effects on Infant Gut Microflora Methods – Fluorescent in situ hybridization (FISH) – Bifidobacterium species characterization Results – Bifidobacteria lower among formula group (P=0.044) – Bifidobacterium composition achieved in infants receiving prebiotic supplemented formula Rinne et al FEMS 2005;43:59-65. 7

10. Bifidobacterium Composition Achieved 8 Rinne et al FEMS 2005;43:59-65.

11. Infant Formula Containing a Mixture of GOS/FOS or Bb-12 Compared to Standard Subjects – 63 pregnant women breastfeeding, 57 not breastfeeding Feeding Groups – Mothers who decided not to breastfeed Standard formula (n=19) Prebiotic formula; GOS/FOS (n-19) Probiotic formula; Bb-12 (n=19) – Breastfeeding Bakker-Zierikzee et al BJN 2005;94:783-790. 9

12. Infant Formula Containing a Mixture of GOS and FOS Results in Higher Bifidobacteria Methods – Questionnaires – FISH Fecal samples Results Bakker-Zierikzee et al BJN 2005;94:783-790. 10

13. GOS/FOS Formula has a Higher Percentage of Bifidobacteria in the Total Bacterial Count 11 Breast milk Standard formula Bb-12 GOS/FOS

14. Where is Research Heading? Development of new prebiotic blend formula Microflora modulation can occur through diets – Is the effect long lasting? – Optimal composition and dosage Clarify specific effects: understand HMO’s benefit for the breastfed infant 12

15. Dietitian’s Role Encouragement of breastfeeding is the first choice Whenever breastfeeding is not possible – Supplemented infant formula provides safe, nutritious, and healthy food for growth and development Keep abreast with the latest research Huerou-Luron et al Nutrition Research Reviews 2010;23:23-36. 13

16. Conclusions Enteral supplementation of a prebiotic mixture does not enhance postnatal decrease in intestinal permeability in preterm infants in the first week of life Infants given partially hydrolyzed formula supplemented with prebiotics had identical levels of Bifidobacteria in feces, exceeding formula fed infants With the aim of stimulating the typical intestinal microflora of breastfed infants in formula fed infants, the effects of adding pre or probiotics to infant formula was compared to a standard formula. Although not statistically significant, GOS/FOS group had higher percentage of Bifidobacteria 14

17. The field is still in its infancy and it has to grow with care … 15

18. References 1.Thomas DW, Greer FR, et al. Probiotics and prebiotics in pediatrics. Pediatrics 2010;126:1217-1231. 2.Mountzouris KC, McCartney AL, Gibson GR. Intestinal microflora of human infants and current trends for tis nutritional modulation. British Journal of Nutrition 2002;87:405-420. 3.Westerbeek EAM,van den Berg A, Lafeber HN, Fetter WPF, van Elburg RM. The effect of enteral supplementation of a prebiotic mixture of non-human milk galacto-, fructo- and acidic oligosaccharides on intestinal permeability in preterm infants. British Journal of Nutrition 2011;105:268-274. 4.Rinne MM, Gueimonde M, Kalliomaki M, Hoppu U, Salminen SJ, Isolauri E. Similar bifidogenic effects of prebiotic-supplemented partially hydrolyzed infant formula and breastfeeding on infant gut microbiota. FEMS 2005;43:59-65. 5.Bakker-Zierikzee AM, Alles MS, Knol J, et al. Effects of infant formula containing a mixture of galacto- and fructo- oligosaccharides or viable Bifidobacterium animalis on the intestinal microflora during the first 4 months of life. BJN 2005;94:783-790. 6.Huerou-Luron IL, Blat S, Boudry G. Breast v. formula-feeding: impacts on the digestive tract and immediate and long term health effects. Nutrition Research Reviews 2010;23:23-36.