Human milk oligosaccharides (HMO) are abundant in human milk (5-20 g/L) (1) and exert numerous beneficial effects (2-4). The two predominant HMO are lacto-N-tetraose (LNT) and 2´-fucosyllactose (2´-FL), although 2´-FL presence depends upon maternal secretor type (1). Bovine milk oligosaccharide content and composition are lower and less complex (5), thus infant formulae are nearly devoid of oligosaccharides (6). Most contain prebiotics, but large scale production has enabled the recent addition of 2´-FL and LNnT to formula (6). Note that LNT type 1 and LNnT type 2 cores differ, which affects their recognition (7) and utilization (8), thus their functionality is likely not identical.

Two randomized clinical trials have investigated adding HMO to formula (9, 10). In the first, infants were fed control formula (CF) or formula containing 0.2 or 1.0 g/L 2´-FL for the first 4 months of life and were compared to a breast-fed (BF) reference (9). All formulae also contained galactooligosaccharides, which was reduced in the 2´-FL formulae to maintain a total oligosaccharide content of 2.4 g/L. Growth, stool consistency or adverse events were similar across treatments (9). Immune outcomes were assessed in these infants using blood samples collected on day of life 42 (11).

Infants fed the 2´-FL formulae did not differ from BF, but had 29 to 83% lower plasma proinflammatory cytokine concentrations than CF-fed infants. In terms of immune cells, BF infants had higher total T-cell and cytotoxic (CD8+) T-cells than CF-fed infants. Total T-cells in infants fed 2´-FL were intermediate between BF and CF, and CD8+ T cells in infants fed 1.0 g/L 2´-FL were intermediate between BF and CF (11).

In the second study, infants received a CF or a formula with 1.0 g/L 2´-FL and 0.5 g/L LNnT for 6 months, after which all were fed the CF until 12 months of age (10). Weight gain and digestive symptoms were similar in both groups, except infants fed HMO had softer stool and fewer nighttime wake-ups at 2 months. Secondary outcomes showed that consuming HMO-supplemented formula reduced parent- reported morbidity (particularly bronchitis) and antipyretics and antibiotics use (10). In addition, the HMO formula shifted the microbiome composition to be more similar to that of BF and increased Bifidobacterium abundance (12). Taken together, supplementing formula with 2´-FL or 2´-FL+LNnT affected infant immunity, reduced infection and medication use, and increased bifidobacteria abundance, thus narrowing the gap between breast-and formula-fed infants.


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