Temporal Associations Between Human Milk Metabolites and the Infant Gut Microbiome and metabolome

IntroductionHuman milk is vital in establishing a healthy infant gut microbiome. Gut microbes and their metabolites are important for host development. However, our understanding of how milk metabolites are connected to the gut microbiome and metabolome in early-life remains limited. We aimed to investigate associations between the human milk metabolome and the gut microbiome in infancy. MethodsThe fecal and milk samples were collected at 2.5 (n=283), 6 (n=129) and 14 (n=65) months of age. Gut microbiota was analyzed with amplicon sequencing, the gut metabolome was analyzed with gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry, and milk metabolites were analyzed with proton nuclear magnetic resonance. ResultsBifidobacterium and other butyrate producers were associated with ethanolamine and methionine level in the milk, in a time-dependent manner. Elevated milk fucosylated oligosaccharide, LNFP-I and caprylate concentrations were positively associated with secondary bile acid levels following the introduction of solid foods. Additionally, acidic oligosaccharides 3-SL and 6-SL were positively associated with long-chain carbohydrates prior to solid food introduction, however negatively associated thereafter. ConclusionOur results highlight that milk metabolites are associated with biologically relevant gut microbial metabolites. Only limited associations were observed between milk composition and the microbiome, which differed between early and late infancy. This suggests milk metabolome may differentially influence microbial metabolism depending on dietary diversity and/or the maturity of the microbiome. ImportanceIts essential to raise awareness about breastfeeding and its variety of health benefits. Expanding our understanding of how human milk small molecules with potential bioactivity interact with the gut microbiome can help highlight these positive effects. Exploratory studies of human milk composition with gut microbial metabolites may support achieving this goal. Furthermore, understanding of biological effects of different components in human milk is important, and it can help to develop strategies to ensure optimal growth and development of an infant regardless of the breastfeeding status of the child.