[Science Update] Relationship between metabolites modulated by HMOs and reduced risk of LRTIs


In relation to the reduced incidence of lower respiratory tract infections (LRTIs) shown in infants fed a 2-HMO formula compared to those fed a control formula, the current study provided unique insights into how HMO feeding affects the developing gut microbiome-host metabolome in early infancy. In this study, the microbiota composition and biochemical species in infant stool (n = 743) from a previous clinical trial were measured.

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  • Control formula: Intact cow’s milk protein-based formula
  • Test formula: Control formula supplemented with 2 HMOs (2’-FL & LNnT) in which 1.5 g/L lactose was replaced by a 2:1 mixture of the 2 HMOs


  • Shotgun metagenomic sequencing
  • Untargeted mass spectrometry metabolomics


  • Major alterations in lipid and amino acid metabolism were caused by the presence of HMOs in the formula, particularly in phospholipid/sphingomyelin metabolism and the gamma-glutamylation and N-acetylation of amino acids
  • HMOs caused alterations in the gut's functional ecology, which were associated to the reduced LRTIs that have been reported
    • A negative correlation between gamma-glutamylated amino acids (GGAAs) and LRTIs was observed
    • Sphingolipids and free amino acids were observed to be positively correlated to later LRTIs
  • There were several statistically significant correlations between the LRTI phenotype or feeding group and the three identified classes of important metabolites, namely GGAAs, N-acetylated-amino acids (NAAs), and sphingolipids
  • Sphinganine and 3-keto-sphinganine had the strongest correlations with Bacteroides species
    • GGAAs had the strongest correlation with Bifidobacterium species, namely, B. bifidum, B. longum subsp. longum, and B. longum subsp. infantis
  • The concentrations in stool calprotectin and elastase and the stool metabolites sphinganine, 3-keto-sphinganine, 5-aminovalerate, butyrate, and propionate were observed to be positively correlated
  • Stool calprotectin and elastase were observed to be negatively associated with the stool metabolites acetate, lactate, fucosyl-glycans and most GGAAs


  • These results expand our knowledge of the infant gut/microbiome co-metabolism in early life and give evidence that such metabolic alterations may affect immune competence at distant mucosal sites like the airways

2’-FL = 2’-Fucosyllactose; LNnT = Lacto-N-Neotetraose

Link to the full article:


Martin FP et al. Host-microbial co-metabolites modulated by human milk oligosaccharides relate to reduced risk of respiratory tract infections. Front Nutr. 2022;9:935711.

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