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

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