Abstract

BackgroundMilk fat globule membrane (MFGM) and lactoferrin (LF) are human-milk bioactive components demonstrated to support gastrointestinal and immune development. Significantly fewer diarrhea and respiratory-associated adverse events through 18 mo of age were previously reported in healthy term infants fed a cow-milk–based infant formula with an added source of bovine MFGM and bovine LF through 12 mo of age.ObjectivesThe aim was to compare microbiota and metabolite profiles in a subset of study participants.MethodsStool samples were collected at baseline (10–14 d of age) and day 120. Bacterial community profiling was performed via 16S rRNA gene sequencing and alpha and beta diversity were analyzed (QIIME 2). Differentially abundant taxa were determined using linear discriminant analysis effect size (LefSE) and visualized (Metacoder). Untargeted stool metabolites were analyzed (HPLC/MS) and expressed as the fold-change between group means (control to MFGM+LF ratio).ResultsAlpha diversity increased significantly in both groups from baseline to 4 mo. Subtle group differences in beta diversity were demonstrated at 4 mo (Jaccard distance; R2 = 0.01, P = 0.042). Specifically, Bacteroides uniformis and Bacteroides plebeius were more abundant in the MFGM+LF group at 4 mo. Metabolite profile differences for MFGM+LF versus control included lower fecal medium-chain fatty acids, deoxycarnitine, and glycochenodeoxycholate, and some higher fecal carbohydrates and steroids (P < 0.05). After applying multiple test correction, the differences in stool metabolomics were not significant.ConclusionsAddition of bovine MFGM and LF in infant formula was associated with subtle differences in stool microbiome and metabolome by 4 mo of age, including increased prevalence of Bacteroides species. Stool metabolite profiles may be consistent with altered microbial metabolism. This trial was registered at https://clinicaltrials.gov as NCT02274883.

Highlights

  • Maturation of the infant immune system and gastrointestinal (GI) tract, including dynamic development of the gut microbiome, establishes the foundation for long-term metabolic and immune health [1]

  • The aim of the present analysis was to examine the impact of bovine MFGM (bMFGM) and bovine lactoferrin (bLF) in infant formula (IF) on stool microbiome and metabolome

  • The microbiota of infants receiving human milk is more stable over time and is characterized by lower alpha diversity compared with infants receiving IF [35]

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Summary

Introduction

Maturation of the infant immune system and gastrointestinal (GI) tract, including dynamic development of the gut microbiome, establishes the foundation for long-term metabolic and immune health [1]. Animals who received formula with added bMFGM displayed significant group differences in ascending colon and stool microbiota [10], as well as higher stool Proteobacteria and reduced Firmicutes [11]. In rat pups receiving formula with added bMFGM, richness and evenness of gut microbial species increased compared with a control formula with added vegetable fat, and the abundance of Firmicutes and Proteobacteria were more similar to a group receiving dam’s milk [3]. Milk fat globule membrane (MFGM) and lactoferrin (LF) are human-milk bioactive components demonstrated to support gastrointestinal and immune development. Conclusions: Addition of bovine MFGM and LF in infant formula was associated with subtle differences in stool microbiome and metabolome by 4 mo of age, including increased prevalence of Bacteroides species.

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