Human milk supports optimal infant development by providing essential nutrients and bioactive compounds, including oligosaccharides, which promote gut microbiota balance and immune function. Current infant formulas lack these oligosaccharides, potentially contributing to differences in outcomes between breastfed and formula-fed infants. This study examined whether bovine milk-derived oligosaccharides (MOS) in infant formula improve gut microbiota composition and intestinal immunity in formula-fed infants compared to breastfed infants.
Methods
This double-blind, randomised controlled trial enrolled 230 healthy, term formula-fed infants aged 21–26 days. Infants received either a control formula (CG) or MOS-supplemented formula (EG, 7.2 g/L) until 6 months of age. Human milk-fed infants (HFI, n=70) served as a reference group. Fecal samples were collected at baseline, 2.5 months, and 4 months to assess gut microbiota composition, metabolic markers, and immune biomarkers.
Results
Gut Microbiota Composition:
By 2.5 and 4 months, the gut microbiota in EG shifted closer to that of HFI. EG showed significantly higher levels of Bifidobacterium spp. compared to CG, approaching levels seen in HFI. MOS particularly promoted species like Bifidobacterium breve and B. longum. Caesarean-born infants in EG exhibited microbiota profiles similar to vaginally delivered HFI, suggesting MOS corrected delivery-associated dysbiosis.
Reduction in Pathogens:
At 4 months, Clostridioides difficile and Clostridium perfringens counts in EG were reduced by ~90% and ~65%, respectively, compared to CG. This reduction was likely driven by bifidobacteria proliferation and associated metabolite production.
Metabolic Effects:
EG had lower fecal pH and higher lactate and acetate concentrations than CG, aligning with HFI profiles. These metabolic changes were linked to improved calcium absorption, indicated by lower fecal calcium excretion in EG and HFI.
Immune Function:
Fecal secretory IgA (sIgA) levels were twice as high in EG compared to CG, approaching HFI levels. Notably, oral poliovirus vaccine-specific IgA was ~50% higher in EG, suggesting improved mucosal immune response. Additionally, EG had lower levels of intestinal inflammation and permeability markers (calprotectin, α-1 antitrypsin, and myeloperoxidase) compared to CG.
Conclusion
The addition of MOS to infant formula improved gut microbiota composition, increased bifidobacteria abundance, reduced pathogenic bacteria, and enhanced intestinal immune response. These outcomes align MOS-supplemented formula-fed infants closer to breastfed infants, particularly in microbiota development and mucosal immunity. MOS supplementation holds promise as a strategy to bridge the gap between formula and human milk.
