Effect of Bovine Milk Fat Globule Membrane and Lactoferrin in Infant Formula on Gut Microbiome and Metabolome at 4 Months of Age

Maciej Chichlowski; Nicholas Bokulich; Cheryl L Harris; Jennifer L Wampler; Fei Li; Carol Lynn Berseth; Colin Rudolph; Steven S Wu

doi:10.1093/cdn/nzab027

Effect of Bovine Milk Fat Globule Membrane and Lactoferrin in Infant Formula on Gut Microbiome and Metabolome at 4 Months of Age

Curr Dev Nutr. 2021 Apr 2;5(5):nzab027. doi: 10.1093/cdn/nzab027. eCollection 2021 May.

Authors

Maciej Chichlowski¹, Nicholas Bokulich², Cheryl L Harris¹, Jennifer L Wampler¹, Fei Li³, Carol Lynn Berseth¹, Colin Rudolph¹, Steven S Wu¹

Affiliations

¹ Medical and Scientific Affairs, Reckitt|Mead Johnson Nutrition Institute, Evansville, IN, USA.
² Laboratory of Food Systems Biotechnology, Institute of Food, Nutrition, and Health, ETH Zürich, Zurich, Switzerland.
³ Departments of Developmental and Behavioral Pediatrics & Child Primary Care, MOE-Shanghai Key Lab for Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.

Abstract

Background: Milk 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.

Objectives: The aim was to compare microbiota and metabolite profiles in a subset of study participants.

Methods: Stool 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).

Results: Alpha diversity increased significantly in both groups from baseline to 4 mo. Subtle group differences in beta diversity were demonstrated at 4 mo (Jaccard distance; R ² = 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.

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. Stool metabolite profiles may be consistent with altered microbial metabolism. This trial was registered at https://clinicaltrials.gov as NCT02274883.

Keywords: formula feeding; infant microbiome; lactoferrin; metabolome; milk fat globule membrane (MFGM).

Associated data

ClinicalTrials.gov/NCT02274883