Karen Harris

Karen Harris is a professional writer and editor with more than two decades of experience in research-driven nonfiction writing. With a background in journalism and a Master's degree in English, she brings a meticulous approach to fact-finding, source evaluation, and clear communication of complex topics. Her work spans health, lifestyle, and consumer education, always with a focus on accuracy and readability.

Context

The milk fat globule membrane (MFGM) is a biologically active component of human and bovine milk, rich in proteins, phospholipids, and glycolipids. It is largely removed during standard infant formula manufacturing. Previous research from this cohort linked MFGM-supplemented formula to a lower incidence of acute otitis media and potentially beneficial immune and metabolic effects. This study investigated whether MFGM supplementation could shift the gut microbiome and metabolome of formula-fed infants closer to that of breastfed infants.

Study Overview

Design: Secondary analysis (fecal microbiome and metabolome sub-study) of a double-blind, parallel-group randomized controlled trial


Population: 90 healthy, full-term infants randomly selected from a cohort of 240 (30 per group: breastfed reference, standard formula, MFGM formula); enrolled in Umeå, Sweden


Follow-up: 12 months (stool samples at 2, 4, 6, and 12 months)


Funding: Funded by Hero (industry); several senior authors are members of Semper and Hero Scientific Advisory Boards and received travel grants


Evidence Certainty (GRADE): Not formally GRADE-rated; exploratory secondary analysis - not powered for microbiome or metabolome outcomes


Comparison:

  • Experimental Formula group (EF, n = 30): Low-energy, low-protein formula supplemented with bovine MFGM concentrate (~0.48 g/L, providing 4% of total protein), from ~2 to 6 months
  • Standard Formula group (SF, n = 30): Standard cow's milk-based formula (BabySemp1), same period
  • Breastfed reference group (BF, n = 30): Non-randomized, exclusively breastfed reference
  • All infants received complementary foods from 4 months onward as per Swedish guidelines; follow-up to 12 months

Key Findings

Gut Microbiome:

  • During the exclusive feeding period (2–6 months), breastfed infants had significantly higher fecal Bifidobacterium abundance compared to both formula groups - a well-established finding.
  • The difference between EF and SF microbiota was minor overall; MFGM supplementation did not meaningfully shift the formula-fed gut microbiome toward the breastfed profile.
  • A higher prevalence of Akkermansia was noted in some EF-fed infants during the exclusive feeding period, though this was not statistically significant across the group.
  • At 12 months, fecal Haemophilus (a genus containing several pathogens) was less prevalent in EF-fed infants compared to SF - a novel finding requiring confirmation.
  • By 12 months, microbiome differences between breastfed and formula-fed infants had largely disappeared across all groups.

Gut Metabolome:

  • A clear and consistent metabolic difference between breastfed and formula-fed infants was observed from 2 to 6 months: breastfed infants showed higher fecal lactate, pyruvate, fucose, 1,2-propanediol, and myo-inositol (markers of carbohydrate/HMO fermentation); formula-fed infants showed higher butyrate, propionate, isobutyrate, isovalerate, and phenylacetate (markers of protein/amino acid fermentation).
  • The EF group showed significantly lower levels of several fecal metabolites compared to SF during the exclusive feeding period, including amino acids (ornithine, isoleucine, glutamate, phenylalanine, tyrosine, valine, glycine), amino acid degradation products, lactate, succinate, and hypoxanthine - suggesting reduced protein fermentation in the gut.
  • This metabolic shift in EF did not, however, fully bridge the gap to the breastfed metabolome profile.
  • After introduction of complementary foods and by 12 months, metabolome differences between all feeding groups became indistinguishable.

Mechanistic Interpretation:

  • The authors hypothesize that higher protein content in standard formula drives amino acid fermentation by gut microbes, raising fecal branched-chain fatty acids and ammonia. The lower protein content of EF (not MFGM itself) likely explains much of the observed metabolic difference between EF and SF.
  • MFGM's glycosylated proteins may provide some fermentable substrate, but the amount supplemented was lower than doses shown to affect microbiome composition in animal studies.

Limitations

  • This is a secondary, exploratory sub-study of a trial not powered for microbiome or metabolome outcomes; findings are hypothesis-generating only.
  • The breastfed group was not randomized - feeding choice introduces uncontrollable confounders.
  • Sample size is small (n = 30 per group), limiting statistical power for microbiome analyses.
  • The EF differed from SF in both MFGM content and protein/energy level, making it impossible to attribute observed effects specifically to MFGM.
  • Volume of human milk consumed and maternal HMO secretor status were not recorded, adding variability to the breastfed group.
  • A large proportion of infants across all groups consumed probiotic products (containing Lactobacillus) during the study, which may have influenced fecal metabolome results.
  • By 12 months, only 6 infants in the breastfed group still had a recorded breastfeeding history, severely limiting 12-month comparisons.
  • Industry-funded; several senior authors have financial relationships with the formula manufacturer.

Neutral Interpretation

This exploratory sub-study demonstrates a clear and expected metabolic distinction between breastfed and formula-fed infant gut environments during the exclusive feeding period, primarily driven by differences in carbohydrate (HMO) availability and protein content. MFGM supplementation had only a moderate impact on the gut microbiome and did not shift the formula-fed microbiota meaningfully toward the breastfed pattern. The observed reductions in amino acid fermentation metabolites in EF-fed infants are interesting but likely reflect the lower protein content of EF rather than a specific MFGM effect. Independent, adequately powered trials with MFGM as the sole variable are needed to draw conclusions about its gut microbiome effects.

Full Citation

He X, Parenti M, Grip T, et al. Fecal microbiome and metabolome of infants fed bovine MFGM supplemented formula or standard formula with breast-fed infants as reference: a randomized controlled trial. Sci Rep. 2019;9:11589. 

PMID: 31406230. 

Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC6690946/

Disclosure

This summary is based on the published full-text study. It is provided for informational purposes only and does not constitute medical advice.