The study, which took place across 18 centers in Europe, found that the synbiotic formula not only increased the abundance of Bifidobacteria, a cornerstone of the infant gut, but also reduced the presence of opportunistic pathogens.
“The synbiotic formula promoted the expansion of beneficial Bifidobacteria, especially infant-type species, in all infants, suggesting the formula could contribute toward minimizing the observed gaps in early microbiome development between formula-fed and breastfed infants,” the researchers wrote in Frontiers in Nutrition.
Funded by Nestlé, the study is the first to provide data on growth, gastrointestinal tolerance and gut microbiome outcomes in response to feeding with a unique infant formula.
Importance of HMOs and beneficial bacteria for infant health
Human milk is packed with oligosaccharides and beneficial bacteria that can positively impact the long-term health of children. Babies who are not breastfed therefore often miss out on these crucial components, with studies showing that infant feeding is an important modifiable risk factor for infant disease.
Since some babies cannot be breastfed, scientists have begun to study the effect of adding probiotic strains and manufactured human milk oligosaccharides to infant formula to assess whether these synbiotic solutions provide health benefits to infants.
In this study, the researchers added two strains of B. infantis and B. lactis to a partially hydrolyzed whey-based formula. They then randomized 313 infants into three groups, with 118 fed the synbiotic formula, 114 fed a control formula (with no probiotic strains or HMOs) and 81 fed breastmilk.
At four months of age, the babies were assessed for weight gain velocity, fecal outcomes (abundance of Bifidobacteria, and immune and gut health markers), gastrointestinal tolerance and adverse events.
Loss of crucial gut bacteria in breastfed babies
Overall, the study showed that the synbiotic formula was safe and well-tolerated and supported healthy, age-appropriate growth up to four months of age.
While weight gain was similar in the synbiotic group compared to the control and breastfed groups, the intervention arm had slightly higher weight-for-age, weight-for-length, height-for-age and length-for-age scores.
Stool consistency and frequency were also similar across the groups, with stool frequency slightly lower in the formula-fed infants compared to the breastfed infants.
However, there was a significant overall expansion of the infant-type species of beneficial Bifidobacteria in the synbiotic group compared to the control group.
The researchers also highlighted that B. infantis was observed only in small amounts in the breastfed group, indicating that there is a ‘general loss’ of this important gut bacteria in modern populations.
“Interestingly, the commensal infant-type Bifidobacteria B. infantis were only rarely observed in breastfed and control infants compared to synbiotic infants through three months,” they wrote. “A similar low prevalence was recently reported in other geographies, which is consistent with the general loss of B. infantis and the reduced capacity for HMO metabolism observed in industrialized settings compared to developing countries.”
The synbiotic group also had a lower presence and abundance of opportunistic pathogens such as toxigenic C. difficile. Based on previous research, the authors suggest this effect is likely due to the HMOs present in the synbiotic formula rather than the probiotics.
‘Maximizing’ the benefits of formula
Overall, the study highlighted the critical role of HMOs and beneficial bacteria in early gut and immune development.
The researchers noted that the research underscores the importance of ‘maximizing’ infant formula solutions to ensure formula-fed babies receive the nutrients they need to optimize growth and overall health.
“Given the importance of breastfeeding for infants to have a healthy, long-term developmental trajectory, it is crucial to maximize the benefits that formula can provide in cases where breastfeeding is not possible,” they wrote.
The study will continue to follow the infants up to 15 months of age, with the next set of results expected in the near future.
Source: Frontiers in Nutrition. doi: 10.3389/fnut.2025.1628847. “Partially hydrolyzed, whey-based infant formula with six human milk oligosaccharides, B. infantis LMG11588, and B. lactis CNCM I-3446 is safe, well tolerated, and improves gut health: a staged analysis of a randomized trial”. Authors: J.C. Picaud, et al.
