Term infant formula supplemented with milk-derived oligosaccharides shifts the gut microbiota closer to that of human milk-fed infants and improves intestinal immune defense: a randomized controlled trial.

The American journal of clinical nutrition. 2022;115(1):142-153

Plain language summary

Human milk is finely attuned to the needs of infants supporting optimal growth and overall development. Infant formula composition is developed after human milk. A promising novel approach to enhance the oligosaccharide profile of infant formulas is the addition of bovine milk-derived oligosaccharides (MOS). The aim of this study was to investigate the effects of a MOS-supplemented infant formula on gut microbiota and intestinal immunity. This study was a randomised, double-blind, controlled trial of 2 formula fed groups and a prospective, observational companion study of human milk-fed infants (HFI). Formula-fed infants (n = 230) were randomly assigned to either the control group (CG) or experimental group (EG). Results showed that adding MOS to infant formula had a strong effect on gut microbiota particularly noticeable was a significant increase in bifidobacteria. Furthermore, the effects of the MOS-supplemented formula on the gut microbiota in caesarean- or vaginally born infants were similar, changing the microbiota towards the composition of vaginally born HFI including an increase in bifidobacteria. Authors conclude that the gut microbiota and intestinal immunity of formula-fed infants can be beneficially modulated by an infant formula with an oligosaccharide profile enhanced by the addition of MOS. Thus, supplementing infant formula with MOS is a promising approach to support the development of the gut microbiota during early infancy in concert with the infant’s immune development.

Abstract

BACKGROUND Bovine milk-derived oligosaccharides (MOS) containing primarily galacto-oligosaccharides with inherent concentrations of sialylated oligosaccharides can be added to infant formula to enhance the oligosaccharide profile. OBJECTIVE To investigate the effects of an MOS-supplemented infant formula on gut microbiota and intestinal immunity. METHODS In a double-blind, randomized, controlled trial, healthy term formula-fed infants aged 21-26 d either received an intact protein cow milk-based formula (control group, CG, n = 112) or the same formula containing 7.2 g MOS/L (experimental group, EG, n = 114) until the age of 6 mo. Exclusively human milk-fed infants (HFI, n = 70) from an observational study served as the reference. Fecal samples collected at baseline, and the ages of 2.5 and 4 mo were assessed for microbiota (16S ribosomal RNA-based approaches), metabolites, and biomarkers of gut health and immune response. RESULTS Aged 2.5 and 4 mo, redundancy analysis (P = 0.002) and average phylogenetic distance (P < 0.05) showed that the overall microbiota composition in EG was different from CG and closer to that of HFI. Similarly, EG caesarean-born infants were different from CG caesarean- or vaginally born infants and approaching HFI vaginally born infants. Relative bifidobacteria abundance was higher in EG compared with CG (P < 0.05) approaching HFI. At the age of 4 mo, counts of Clostridioides difficile and Clostridium perfringens were ∼90% (P < 0.001) and ∼65% (P < 0.01) lower in EG compared with CG, respectively. Geometric LS mean (95% CI) fecal secretory IgA in EG was twice that of CG [70 (57, 85) compared with 34 (28, 42) mg/g, P < 0.001] and closer to HFI. Fecal oral polio vaccine-specific IgA was ∼50% higher in EG compared with CG (P = 0.065). Compared with CG, EG and HFI had lower fecal calcium excretion (by ∼30%, P < 0.005) and fecal pH (P < 0.001), and higher lactate concentration (P < 0.001). CONCLUSIONS Infant formula with MOS shifts the gut microbiota and metabolic signature closer to that of HFI, has a strong bifidogenic effect, reduces fecal pathogens, and improves the intestinal immune response.

Lifestyle medicine

Fundamental Clinical Imbalances : Digestive, absorptive and microbiological
Patient Centred Factors : Mediators/Gut microbiota
Environmental Inputs : Diet ; Nutrients ; Microorganisms
Personal Lifestyle Factors : Nutrition
Functional Laboratory Testing : Stool
Bioactive Substances : Oligosaccharides ; Bifidobacteria

Methodological quality

Jadad score : 5
Allocation concealment : Yes

Metadata