Infant formula with cow's milk fat and prebiotics affects intestinal flora, but not the incidence of infections during infancy in a double-blind randomized controlled trial

Antonia Nomayo, Andreas Schwiertz, Rainer Rossi, Katharina Timme, Janine Foster, Richard Zelenka, Josef Tvrdik, Frank Jochum, Antonia Nomayo, Andreas Schwiertz, Rainer Rossi, Katharina Timme, Janine Foster, Richard Zelenka, Josef Tvrdik, Frank Jochum

Abstract

Background: The postnatal intestinal colonization of human milk-fed and formula-fed infants differs substantially, as does the susceptibility to infectious diseases during infancy. Specific ingredients in human milk, such as prebiotic human milk oligosaccharides and a specifically structured fat composition with high proportion of beta-palmitic acid (beta-PA) promote the growth of intestinal bifidobacteria, which are associated with favorable effects on infants' health. The present study investigates whether addition of prebiotic galactooligosaccharides (GOS) in combination with higher amounts of beta-PA from cow's milk fat in infant formula positively affects gut microbiota and the incidence of infections in formula-fed infants.

Methods: In a double-blind controlled trial, formula-fed infants were randomly assigned to either receive an experimental formula containing a higher proportion of beta-PA (20-25%) from natural cow's milk fat, and a prebiotic supplement (0.5 g GOS/100 ml), or a standard infant formula with low beta-PA (< 10%), without prebiotics. A breast-fed reference group was also enrolled. After 12 weeks, fecal samples were collected to determine the proportion of fecal bifidobacteria. The number of infections during the first year of life was recorded.

Results: After 12 weeks, the proportion of fecal bifidobacteria was significantly higher in infants receiving formula with high beta-PA and GOS compared to control, and was similar to the breast-fed group (medians 8.8%, 2.5%, and 5.0% respectively; p < 0.001). The incidence of gastrointestinal or other infections during the first year of life did not differ between groups.

Conclusions: The combination of higher amounts of beta-PA plus GOS increased significantly the proportion of fecal bifidobacteria in formula-fed infants, but did not affect the incidence of infections.

Trial registration: The study protocol was registered with Clinical Trials (Protocol Registration and Results System Trial ID: NCT01603719 ) on 05/15/2012 (retrospectively registered).

Keywords: Beta-palmitic acid; Bifidobacteria; Galactooligosaccharides; Immunity; Microbiota.

Conflict of interest statement

AN and JF have received honoraria and/or non-financial support from the sponsor (DMK Baby, formerly Humana GmbH). FJ received honoraria and/or non-financial support for scientific and educational activities from Humana GmbH, Nestle, and Fresenius Kabi. Their institution was receiving funding sources covering staff costs from Humana GmbH at the time of study conduction. The contribution of FJ to the study was further financed by the board resources supported by the Ev. Waldkrankenhaus Spandau—which is a non-profit hospital.

RZ is an employee of the sponsor DMK Baby Co. Ltd., Bremen, Germany, formerly Humana GmbH.

For the remaining authors, no competing interests are declared.

Figures

Fig. 1
Fig. 1
Flow diagram of study participants. HbPA+ formula = formula supplemented with galactooligosaccharides and fat blend with cow’s milk fat, vegetable, and fish oil (modified to contain 20–25% of beta-palmitic acid); control formula = formula not containing GOS, fat blend containing vegetable, and fish oil without cow’s milk fat. *2 participants in the hbPA+ group were retrospectively excluded due to recruitment error (did not meet inclusion criteria). **analysis of secondary endpoints “infection rates during 12-week intervention”
Fig. 2
Fig. 2
Stool microbiota. Boxplots of median percentages of fecal bifidobacteria on total stool bacteria among feeding groups. Stool microbiota was determined by real-time PCR using selective primers to recognize the genus Bifidobacterium and total bacteria. High-bPA+ group = participants receiving formula with high beta-PA and GOS supplement, control group = participants receiving standard infant formula, BF group = breast-fed reference group; *percentage of bifidobacteria in the control formula group was significantly lower than in the hbPA+ formula and breast milk groups (p = 0.0005), respectively; difference between breast milk and verum formula group was not significant

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