Researchers in China, South Korea and the USA suggested that the evidence paves the way for integrative nutritional strategies in early childhood and the development of next-generation synbiotic formulations.
The 12-week trial involving 390 toddlers compared the effects of a synbiotic supplement or probiotic alone on common conditions such as diarrhea, eczema and respiratory infections.
“Probiotics alone were associated with beneficial clinical effects, while the combination of probiotics and 2’-FL showed a consistent trend toward broader protective effects,” the researchers wrote in the journal Frontiers in Nutrition.
“These findings are consistent with current pediatric microbiome and nutrition research indicating that microbiota-directed interventions can contribute to common diseases risk reduction in early childhood,” they added.
Supporting the infant gut
During the first three years of life, the microbiome develops from a low-diversity community to a more complex, stable and mature ecosystem.
HMOs from breast milk are a primary driver of the colonization of the newborn gut. HMOs serve as prebiotics to nourish beneficial bacteria such as Bifidobacterium infantis.
Early colonization with Bifidobacteria supports childhood immune function. Previous studies have demonstrated that Bifidobacterium probiotics can improve levels of secretory immunoglobulin A (SIgA), the gut’s first line of defense, and decrease markers of inflammation.
Emerging evidence suggests that probiotics can also work via the gut-skin axis and gut-lung axis, helping to lower the risk of common conditions such as eczema and upper respiratory tract infections.
Synbiotics combine probiotics such as bifidobacteria and prebiotics such as HMOs into a single formulation. They have gained interest for their ability to help beneficial bacteria survive in the digestive tract and to generate short-chain fatty acids (SCFAs) that fuel the gut cells and lower inflammation.
Study details
The multi-center, randomized controlled trial involved 390 healthy toddlers aged 1-3 years. They consumed a synbiotic containing the HMO 2′-fucosyllactose (2′-FL) with infant-adapted Bifidobacterium strains, a probiotic with identical strains and doses, or a placebo for 12 weeks, with a 12-week follow-up.
The primary outcome was the incidence of upper respiratory tract infections (URTIs) over 24 weeks, and secondary outcomes included pneumonia, diarrhea, eczema, antibiotic use, gut microbiota, and fecal immune biomarkers.
The findings showed that, compared with placebo, the HMO probiotics group had lower rates of URTIs, pneumonia, diarrhea, and eczema; fewer symptom-days for several respiratory and gastrointestinal manifestations; and fewer antibiotic-use days.
Adjusted differences between the synbiotic group and the probiotic group did not reach statistical significance. Still, the researchers wrote that the combination “showed a consistent pattern of greater effect magnitude across most outcomes.”
In addition, the synbiotic reduced the inflammatory marker fecal calprotectin and increased SIgA, indicating that the combination “enhanced intestinal immune homeostasis, the researchers wrote.
The researchers also noted that 2’-FL may have utility beyond microbiota regulation, serving as “soluble decoy receptors that inhibit the adhesion of pathogens to the intestinal epithelium”.
They noted that larger studies are necessary to determine if 2’-FL has additional benefits beyond those achieved with probiotics alone.
Source: Frontiers in Nutrition. doi: 10.3389/fnut.2026.1856180; “Precision synbiotic intervention with 2′-fucosyllactose and infant-derived Bifidobacterium modulates gut-immune axis and reduces disease risk in toddlers: a randomized controlled trial.” Authors: K. Chen et al.
