Weaned children may still benefit from human milk oligosaccharides

A pooled sample of human milk oligosaccharides (HMOs) may offer numerous benefits for post-weaned children.
"This study has advanced our understanding of the health-enhancing properties of HMOs while highlighting the need for further studies on the efficacy of incorporating individual structures into infant formula, particularly when aiming to modulate the gut microbiota," wrote scientists from the Human Milk Institute at the University of California San Diego. (Getty Images/Image Source)

A pooled sample of human milk oligosaccharides (HMOs) from the breastmilk of several women may offer numerous benefits for post-weaned children.

According to a new study published in Microbiome, these benefits include an increase in numerous beneficial bacteria populations.

“Overall, these shifts in the microbial communities induced by pHMOs treatment highlight their potential to enhance the health of young children by positively modulating their gut microbiota,” wrote researchers from the Human Milk Institute at the University of California San Diego.

The study also compared pHMOs to 2’-FL, the widely commercialized HMO used in infant formula, and found that 2’-FL did not have any significant benefits in post-weaned children.

Benefits of HMOs

HMOs—structurally diverse complex carbohydrates and the third largest solid component of human milk—can help to promote gut barrier function, inhibit potential pathogens and facilitate development of children’s immune systems.

Due to its benefits, some formula companies add synthetic versions of HMOs into their products. 2’-FL, one of the most abundantly secreted HMOs and one that has been commercially available for several years, is the most widely used in infant formula. Previous research has shown that HMO-supplemented formula resulted in fewer respiratory tract infections and a reduced use of antibiotics compared to normal formula for infants.

While the benefits of its addition in formula are well reported, there is not much research on the effects of HMOs on post-weaned children. More information could help to modulate post-weaned developing gut microbiota, the authors write.

Study details

This study analyzed fecal-derived microbial communities of seven children between the ages of 18 and 24 months. The children all carried the antigen alleles associated with an increased risk of developing type-1 diabetes.

The experiment was conducted via bioreactors designed to model the human distal colon, and milk from several women was combined. The pooled HMOs, which included the same amount of 2’FL as the FL group, also contained 18 other HMOs.

Analysis was conducted via genomic DNA sequencing, taxonomic profiling, microbial isolation, HMO utilization assays and metabonomic profiling.

Microbial shifts

Following exposure to pHMOs, there were significant shifts in the microbial community composition and metabolic output. An increase in abundance of bacteroides and health-associated metabolites was reported. Some genera that expanded most included Bacteroides, Ruminococcus and Escherichia-Shigella. Other, non-beneficial populations declined, such as Sutterella, Parasutterella and Sellimonas.

At the species level, pHMO supplementation was associated with increases in Faecalibacterium prausnitzii, Alistipes onderdonkii, Tyzzerella nexilis and Bifidobacterium spp.

Metabolic responses included elevated production of SCFA, acetate and other organic acids that serve essential functions as nutrient sources and influences of host cell gene expression. SCFAs can stimulate intestinal epithelial cells and immune cells to help promote the production of anti-inflammatory cytokines.

In contrast, the 2’FL treatment alone did not induce any genus-level changes.

The researchers noted that “this suggests that only a subset of post-weaned infants may harbor Bifidobacterium strains capable of fermenting 2’FL.”

The fact that microbial communities in this study were able to hydrolyze HMO structures suggests “that HMO-utilizing genes persist in the gut microbiota beyond weaning,” they wrote.

“Overall, our study demonstrates the capacity of the gut microbiota of post-weaned young children to metabolize HMOs and derive benefits from their metabolism.”


Source: Microbiome, 2025, 13(44) doi: 10.1186/s40168-025-02034-9. “Modulating the developing gut microbiota with 2’-fucosyllactose and pooled human milk oligosaccharides.” Authors: S. Renwick, S., et al.