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Evidence-Based Supplement Research
Evidence-Based Supplement Research

Mixed feeding and mode of birth modulate the effects of a hydrolyzed synbiotic formula on the gut microbiome in infants at risk of atopic disease.

  • 2026-08
  • Clinical nutrition ESPEN 74
    • Evangelia Intze
    • Monika Schaubeck
    • Bianca M Arendt
    • Manja Fleddermann
    • Kirsten Beyer
    • Thomas Clavel
    • Ilias Lagkouvardos
    • Thomas C A Hitch

Study Design

Type
Randomized Controlled Trial (RCT)
Population
342 healthy term infants
Methods
Randomized controlled trial; infants received synbiotic infant formula manufactured from extensively hydrolyzed (eHF) or intact protein (control formula; CF) as exclusive formula feeding or as mixed feeding (MF) with human milk; stool samples at 4 and 12 months of age analyzed by 16S rRNA gene amplicon sequencing
Duration
from 4 to 12 months of age
Funding
Unclear

Background and aims

Intestinal colonization by microbial communities is important for infant health. Little knowledge about the effect of infant formula matrix (i.e. form of protein) on the infant microbiome is available. The main aim of this study was to investigate how mode of birth, cessation of breastfeeding, and the formula matrix i.e. protein matrix of synbiotic infant formulas modulate intestinal colonization in infants.

Methods

Stool microbiota profiles of 342 healthy term infants participating in a randomized controlled trial were studied. Infants received synbiotic infant formula manufactured from extensively hydrolyzed (eHF) or intact protein (control formula; CF) as exclusive formula feeding or as mixed feeding (MF) with human milk. Stool samples at 4 and 12 months of age were analyzed by 16S rRNA gene amplicon sequencing.

Results

Phylogenetic profiles of the stool microbiota showed age-dependent maturation. Protein hydrolyzation had only minor effects on overall community types. However, compared to CF, eHF feeding was linked to a Bifidobacterium-dominated microbiota at 4 months of age in two subgroups: in infants born by Cesarean section and those who had received MF for less than 3 months.

Conclusion

In this comparison of two synbiotic infant formulas, the formula matrix based on hydrolyzed protein was linked to a Bifidobacterium-dominated community, dependent on birth and feeding mode. Because bifidobacteria are positively linked to infant health and allergy-prevention, further studies are needed to confirm these results and to investigate the effects on clinical outcomes.

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