Effects of Fortified Formula Milk Supplementation on Neurocognitive Development and the Microbiota-Gut-Brain Axis in

Yifan Gong1,2, Xingwen Zhao3, Qi Zhang2

  • 1College of Food Science and Engineering, Gansu Agricultural University, Lanzhou 730070, China.

Nutrients
|April 14, 2026
PubMed

Insights

Fortified formula milk enhanced processing speed in preschoolers, linked to gut bacteria changes and improved propanoate metabolism. This suggests a role for the microbiota-gut-brain axis in early childhood cognitive development.

Area of Science:

  • Neuroscience
  • Microbiology
  • Nutritional Science

Background:

  • Preschool neurodevelopment is crucial, but research on fortified formula's impact and microbiota-gut-brain axis mechanisms is limited.
  • Understanding how nutrition influences cognitive development in early childhood is essential.

Purpose of the Study:

  • To evaluate the effect of multi-nutrient fortified formula on neurodevelopment in preschool children.
  • To explore potential microbiota-gut-brain axis mechanisms underlying these effects.

Main Methods:

  • A 9-month cluster-randomized, double-blind, controlled trial involving 120 healthy children aged 3-6 years.
  • Neurocognitive function assessed using WPPSI-IV; gut microbiota and fecal metabolomes analyzed.
  • Safety evaluated via anthropometry and blood biochemistry.

Main Results:

  • No significant difference in Full Scale Intelligence Quotient, but significant improvement in Processing Speed Index (PSI) in the intervention group.
  • Increased gut microbial alpha diversity and Bifidobacterium abundance observed.
  • Elevated fecal 2-hydroxybutyric acid (2-HB) linked to propanoate metabolism; both Bifidobacterium and 2-HB positively associated with PSI improvement.

Conclusions:

  • Fortified formula milk improved processing speed in preschoolers.
  • This improvement is associated with gut ecosystem modulation, including Bifidobacterium enrichment and altered propanoate metabolism.
  • Preliminary evidence supports the microbiota-gut-brain axis role in nutritional cognitive programming in early childhood.
Abstract

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