Longitudinal Profiles of Dietary and Microbial Metabolites in Formula- and Breastfed Infants

Abstract

The early-life metabolome of the intestinal tract is dynamically influenced by colonization of gut microbiota which in turn is affected by nutrition, i.e. breast milk or formula. A detailed examination of fecal metabolites was performed to investigate the effect of probiotics in formula compared to control formula and breast milk within the first months of life in healthy neonates. A broad metabolomics approach was conceptualized to describe fecal polar and semi-polar metabolites affected by feeding type within the first year of life. Fecal metabolomes were clearly distinct between formula- and breastfed infants, mainly originating from diet and microbial metabolism. Unsaturated fatty acids and human milk oligosaccharides were increased in breastfed, whereas Maillard products were found in feces of formula-fed children. Altered microbial metabolism was represented by bile acids and aromatic amino acid metabolites. Elevated levels of sulfated bile acids were detected in stool samples of breastfed infants, whereas secondary bile acids were increased in formula-fed infants. Microbial co-metabolism was supported by significant correlation between chenodeoxycholic or lithocholic acid and members of Clostridia. Fecal metabolites showed strong inter- and intra-individual behavior with features uniquely present in certain infants and at specific time points. Nevertheless, metabolite profiles converged at the end of the first year, coinciding with solid food introduction.

Urine Metabolomic Profile of Breast- versus Formula-Fed Neonates Using a Synbiotic-Enriched Formula

“…According to in vivo studies in weanling rats, higher concentrations of secondary bile acids (i.e., deoxycholic acid) were determined in the formula fed group. In line with our results, secondary bile acids may be representative metabolic products of probiotics, such as Bifidobacteria , or bacterial communities, such as Clostridia and Firmicutes , in FF infants from 1st to 3rd month of life [ 56 ].…”

“…In particular, primary and conjugated bile acids, key regulators in the formation of gut microecology by participating in bacterial metabolism, were detected in high amounts in healthy neonates [ 54 ]. Secretion of bile acids (mainly sulfated) is elicited by the presence of human milk lipids and is indirectly associated with increased presence of Veillonella , Bacteroides , Clostridium , Enterobacteriaceae and Streptococcus taxa in BF newborns [ 55 , 56 ]. According to in vivo studies in weanling rats, higher concentrations of secondary bile acids (i.e., deoxycholic acid) were determined in the formula fed group.…”

Open Search of Peptide Glycation Products from Tandem Mass Spectra

“…Due to its high specificity, sensitivity, and speed, mass spectrometry (MS) has been a cornerstone of glycation product analysis for several decades. − Many methods have been developed for the analysis of glycation products. − High-resolution MS techniques enable simultaneous detection and identification of both early and advanced glycation products even in complex mixtures. − This makes high-resolution MS particularly suitable for non-targeted glycation studies . The highly accurate precursor mass and fragmentation behavior are powerful features for structure elucidation and diagnostic fragment identification. − Challenges in non-targeted analysis including the lack of commercial standards and the diversity of structures can be tackled using isotope labeling. − …”

A Pilot Study Exploring Temporal Development of Gut Microbiome/Metabolome in Breastfed Neonates during the First Week of Life

“…Various sterol lipids, glycerophospholipids and fatty acids additionally account for metabolites discriminating between infants of various feeding modalities [ 25 26 27 35 ]. We observed palmitic acid, oleic acid, stearic acid and linoleic acid to be the predominant lipids comprising the infant stool fatty acid profiles.…”

“…Other studies have also demonstrated that breastfeeding alters the metabolic profile until about one year of age, at which point it has been postulated that the predominance of a solid food diet is responsible for the convergence. The analysis of infant fecal metabolite profiles may suggest that the overall variability demonstrated by each individual infant may reflect the interplay between genetic backgrounds and external influences, including the composition of maternal breast milk, amount consumed, and living environment [ 12 35 ].…”