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Clinical Paper: Bosheva M. et al. 2022

Infant Formula With a Specific Blend of Five Human Milk Oligosaccharides Drives the Gut Microbiota Development and Improves Gut Maturation Markers: A Randomized Controlled Trial

5 mins

Human milk oligosaccharides (HMOs) have important biological functions for a healthy development in early life.


This study aimed to investigate gut maturation effects of an infant formula containing 5 HMOs (2’-fucosyllactose, 2’,3-di-fucosyllactose, lacto-N-tetraose, 3’-sialyllactose, and 6’-sialyllactose).


In a multicenter study, healthy infants (7–21 days old) were randomly assigned to:

  • A standard cow’s milk-based infant formula (control group, CG);
  • The same formula with 1.5 g/L HMOs (test group 1, TG1);
  • Or with 2.5 g/L HMOs (test group 2, TG2).
  • A human milk-fed group (HMG) was enrolled as a reference.

Fecal samples collected at baseline (n∼150/formula group; HMG n = 60), age 3 months (n∼140/formula group; HMG n = 65) and 6 (n∼115/formula group; HMG n = 60) months were analyzed for microbiome (shotgun metagenomics), metabolism, and biomarkers.


At both post-baseline visits, the microbiota composition of two test groups was different (p<0.01) and coordinates were closer to the breast-fed reference group microbiota compositions in the two test groups (TGs) compared to CG (P < 0.01) with coordinates closer to that of HMG. The relative abundance of Bifidobacterium longum subsp. infantis (B. infantis) was higher in TGs vs. CG (P < 0.05; except at 6 months: TG2 vs. CG P = 0.083). Bifidobacterium abundance was higher by ∼45% in TGs vs. CG at 6-month approaching HMG. At both post-baseline visits, toxigenic Clostridioides difficile abundance was 75–85% lower in TGs vs. CG (P < 0.05) and comparable with HMG. Fecal pH was significantly lower in TGs vs. CG, and the overall organic acid profile was different in TGs vs. CG, approaching HMG. At 3 months, TGs (vs. CG) had higher secretory immunoglobulin A (sIgA) and lower alpha-1-antitrypsin (P < 0.05). At 6 months, sIgA in TG2 vs. CG remained higher (P < 0.05), and calprotectin was lower in TG1 (P < 0.05) vs. CG.


Infant formula with a specific blend of 5 HMOs supports the development of the intestinal immune system and gut barrier function and shifts the gut microbiome closer to that of breastfed infants with higher bifidobacteria, particularly B. infantis, and lower toxigenic Clostridioides difficile.


We believe that breastfeeding is the ideal nutritional start for babies and we fully support the World Health Organization’s recommendation of exclusive breastfeeding for the first six months of life followed by the introduction of adequate nutritious complementary foods along with continued breastfeeding up to two years of age. We also recognise that breastfeeding is not always an option for parents. We recommend that healthcare professionals inform parents about the advantages of breastfeeding. If parents choose not to breastfeed, healthcare professionals should inform parents that such a decision can be difficult to reverse and that the introduction of partial bottle-feeding will reduce the supply of breast milk. Parents should consider the social and financial implications of the use of infant formula. As babies grow at different rates, healthcare professionals should advise on the appropriate time for a baby to begin eating complementary foods. Infant formula and complementary foods should always be prepared, used and stored as instructed on the label in order to avoid risks to a baby’s health. The product should be used only on the advice of independent persons having qualifications in medicine, nutrition, pharmacy, or other professionals responsible for maternal and child care.