HMOs play key roles in infant health by acting as prebiotics, preventing infections, and regulating the immune system.
The physiological benefits of HMOs are, at least partly, mediated by metabolites such as acetate and aromatic lactic acids (ALAs), produced during the utilization of HMOs by infant-type human-residential bifidobacteria (HRB).
However, the effects of HMOs on the gut microbiota of infants who lack HRB with HMO-utilizing ability, or on children over 3 years old after the decrease of infant-type HRB, have not been widely investigated.
A study conducted by Morinaga Milk Industry sought to find out the effects of HMO alone or in combination with Bifidobacterium longum subsp. infantis M-63 (B. infantis M-63) on the gut microbiota of infants and young children, specifically focusing on the prebiotic effects using a fecal culture system.
Changes in the production of HRB-associated metabolites, such as short chain fatty acids (SCFAs), lactate and ALAs, were also evaluated.
A pH-controlled single-batch fermenter was used to model the human gut microbiota, and fecal fermentation was conducted with 2’-FL, with or without supplementation with B. infantis M-63.
“We selected 2’-FL as it is one of the most abundant HMOs in human milk, and is the most commonly used in infant and young child formulas,” the authors wrote.
The fecal fermentation results showed that infants supplemented with 2’-FL alone led to a striking difference in response—one infant had a significant increase in bifidobacteria, two infants showed a slight increase, and one infant showed almost no response. Approximately 80% of 2’-FL in the culture media remained unconsumed.
In contrast, the combination of 2’-FL and B. infantis M-63 significantly increased bifidobacteria and promoted acetate and ALA production in all four infants. Correspondingly, 2’-FL in the fermentation media was completely consumed.
All infants in this study were breastfed. This indicates that even among breastfed infants, not all have Bifidobacterium capable of utilizing 2’-FL and hence, do not fully benefit from it.
Therefore, the co-administration of infant-type HRB with a high HMO-utilizing capacity, such as B. infantis M-63, could be an effective solution to this issue.
Effects on young children
In this study, the detected Bifidobacterium species were primarily B. longum and B. breve in infants, and B. longum, B. breve and B. catenulatum group in young children.
Specifically, all infants had either B. longum or B. breve, alone or both, and one infant had B. bifidum. All young children had B. longum, B. breve, and B. catenulatum group, with one individual additionally carrying B. bifidum and another having B. adolescentis group.
Given that HMO-utilization pathways in bifidobacteria vary at the species or even strain level, such individual variations are thought to be related to differences in the response to HMO.
In the fermentation with the feces of young children, an increase in bifidobacteria was not observed with supplementation of 2’-FL. This finding reaffirms the interspecies and inter-strain variations in the HMO-utilizing capacity of bifidobacteria within the same species.
Furthermore, it suggests that a shift from strains with high HMO-utilizing capacity to those with lower capacity within the same species occurs during the transition from infants to young children, marked by the cessation of breastfeeding.
HMOs can be utilized by certain bacterial groups other than bifidobacteria. In the 2’-FL-only group of the young children, an increase in Bacteroides and Streptococcus was observed accompanied by consumption of the added 2’-FL. This suggests that 2’-FL can be utilized by these bacteria.
Conversely, in the 2’-FL and B. infantis M-63 group, a bifidogenic effect and the promotion of acetate and ALA production were observed in young children.
As with the infants, the co-administration of infant-type HRB with a high HMO-utilizing capacity alongside 2’-FL is effective in providing the benefits of 2’-FL to young children beyond the age of three. However, the impact for young children was slightly weaker compared to that for infants.
For example, in the 2’-FL and B. infantis M-63 group, although the occupancy rate of bifidobacteria reached nearly 70% in infants, it was only about 20% in young children.
This may be due to potential competition between M-63 and other bacteria capable of utilizing 2’-FL in the gut of young children, such as Bacteroides or Streptococcus, or because the gut microbial environment of young children may not be suitable for bifidobacteria to utilize 2’-FL.
Clarifying this point in future studies is expected to provide a comprehensive view of HMO metabolism in the guts of infants and young children, as well as insights into the adaptation of the gut microbiota to dietary prebiotics.
“Taken together, these results suggest that to ensure that infants and young children receive the full health benefits of HMOs, it is crucial to have Bifidobacterium with high HMO-utilization capacity, such as B. infantis, in the gut. In the absence of these bacteria, oral supplementation with probiotic strains may be an effective strategy,” the researchers said.
“In addition, these findings may provide new insights for the improvement of infant and young child formulae.”
Source: Frontiers in Nutrition. doi: doi.org/10.3389/fnut.2026.1744839. “Synbiotic effects of 2’-fucosyllactose and Bifidobacterium longum subsp. infantis M-63 in fermented human fecal communities”. Authors: Shijir Xijier Mingat, et al.
