Neonatal diet alters fecal microbiota and metabolome profiles at different ages in infants fed breast milk or formula

Am J Clin Nutr. 2020 Jun 1;111(6):1190-1202. doi: 10.1093/ajcn/nqaa076.

Abstract

Background: Neonatal diet has a large influence on child health and might modulate changes in fecal microbiota and metabolites.

Objectives: The aim is to investigate fecal microbiota and metabolites at different ages in infants who were breastfed (BF), received dairy-based milk formula (MF), or received soy-based formula (SF).

Methods: Fecal samples were collected at 3 (n = 16, 12, and 14, respectively), 6 (n = 20, 19, and 15, respectively), 9 (n = 12, 11, and 12, respectively), and 12 mo (n = 14, 14, and 15, respectively) for BF, MF, and SF infants. Infants that breastfed until 9 mo and switched to formula were considered as no longer breastfeeding at 12 mo. Microbiota data were obtained using 16S ribosomal RNA sequencing. Untargeted metabolomics was conducted using a Q-Exactive Hybrid Quadrupole-Orbitrap mass spectrometer. The data were analyzed using R (version 3.6.0) within the RStudio (version 1.1.463) platform.

Results: At 3, 6, and 9 mo of age BF infants had the lowest α-diversity, SF infants had the highest diversity, and MF was intermediate. Bifidobacterium was 2.6- to 5-fold lower in SF relative to BF infants through 1 y of life. An unidentified genus from Ruminococcaceae higher in the SF (2%) than in the MF (0.4%) and BF (0.08%) infants at 3 mo of age was observed. In BF infants higher levels of butyric acid, d-sphingosine, kynurenic acid, indole-3-lactic acid, indole-3-acetic acid, and betaine were observed than in MF and SF infants. At 3 mo Ruminococcaceae was positively correlated to azelaic, gentisic, isocitric, sebacic, and syringic acids. At 6 mo Oscillospira was negatively correlated with 3-hydroxybutyric-acid, hydroxy-hydrocinnamic acid, and betaine whereas Bifidobacterium was negatively associated with 5-hydroxytryptamine. At 12 mo of age, Lachnospiraceae was negatively associated with hydroxyphenyllactic acid.

Conclusions: Infant diet has a large impact on the fecal microbiome and metabolome in the first year of life.This study was registered at clinicaltrials.gov as NCT00616395.

Keywords: breastfeeding; formula diets; immune system; metabolites; microbiota.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bacteria / classification
  • Bacteria / genetics
  • Bacteria / isolation & purification
  • Bottle Feeding*
  • Breast Feeding*
  • Feces / microbiology*
  • Female
  • Gastrointestinal Microbiome*
  • Humans
  • Infant
  • Infant Formula / analysis
  • Male
  • Metabolome*
  • Milk, Human / metabolism*

Associated data

  • ClinicalTrials.gov/NCT00616395