The PRESTO study: Exploring the role of synbiotics in cow's milk allergy

Cow’s milk allergy (CMA) is one of the most common food allergies in early childhood, affecting infants during a critical period of growth and development. While many children eventually outgrow the condition, CMA can place a significant burden on both infants and their families, often requiring specialized diets, careful symptom management and regular medical care. 

“At Danone Research & Innovation (Danone R&I), our multidisciplinary teams are investigating how early life nutrition may help address the challenges of CMA, not only by managing symptoms and meeting an infant’s nutritional needs, but also by shaping the developing gut microbiota,” says Maaike den Os, Clinical Study Researcher in Specialized Paediatrics. “One example of our work is the PRESTO study, which explored the role of synbiotics in children with CMA, including their effects on the gut microbiota and longer-term health outcomes”.

CMA occurs when the immune system mistakenly reacts to proteins naturally present in cow’s milk, such as casein and whey. Clinical manifestations can range from skin (e.g: eczema) and gastrointestinal symptoms (e.g: diarrhoea and vomiting) to more severe allergic reactions (e.g: anaphylaxis).

For infants who cannot be exclusively breastfed, specialized formulas are an important part of dietary management. “Healthcare professionals may recommend an amino acid-based formula for those with severe symptoms or complex nutritional needs,” explains Annelot Breedveld, Scientist in Allergy. 

Our experts are becoming increasingly interested in the connection between nutrition, the gut microbiota, and immune development. “Synbiotics may support beneficial gut bacteria, helping to bring the gut environment closer to that observed in healthy breastfed infants,” notes Annelot.

To better understand their potential role in CMA management, Danone R&I conducted PRESTO, a long-term clinical study that followed 169 formula-fed infants with CMA across 18 sites worldwide. Over a 12-month period, infants received either an amino acid-based formula alone or the same formula enriched with synbiotics. Researchers then monitored the children for several years, with stool, saliva and blood samples collected at regular intervals to assess long-term health outcomes, gut microbiota composition and the development of tolerance to cow’s milk.

Children in both groups developed tolerance to cow's milk at similar rates over time, indicating that synbiotics did not alter the natural course of CMA outgrowth. However, Infants receiving the synbiotic-containing formula showed a gut microbiota composition more similar to that observed in healthy breastfed infants and experienced fewer infection-related hospitalisations. Additionally, long-term follow-up data showed that children in both groups had eating behaviours comparable to those of healthy peers at six years of age.

“These insights contribute to a growing body of research exploring how nutrition can support infants with CMA beyond symptom management alone,” Annelot highlights. “While synbiotics did not influence the natural development of tolerance to cow’s milk in this study, they may offer broader benefits by promoting beneficial gut bacteria and a microbiota profile more closely aligned with patterns reported in healthy breastfed infants.” 

PRESTO is part of Danone R&I’s broader research program that explores how specialized nutrition can support infants with CMA. Building on these findings, ongoing studies - such as the SMASH study - are investigating the potential of additional biotics and HMOs to deepen our understanding of how early-life nutrition may contribute to healthy growth and development.

Learn more about our research on allergies, gut health and HMOs.

1. Chatchatee P. et al. (2025) Effects of a specific synbiotic blend on fecal short-chain fatty acids and gut inflammation in cow's milk-allergic children receiving amino acid-based formula during early life: results of a randomized controlled trial (PRESTO study). Front Allergy 6; https://doi.org/10.3389/falgy.2025.1667162
2. Chatchatee P. et al. (2024) Tolerance development in cow's milk-allergic children receiving amino acid-based formula with synbiotics: 36-Months follow-up of a randomized controlled trial (PRESTO Study). J Pediatr Gastroenterol Nutr 78(3):699-703. https://doi.org/10.1002/jpn3.12104
3. Chatchatee P. et al. (2022) Tolerance development in cow's milk-allergic infants receiving amino acid-based formula: A randomized controlled trial. J Allergy Clin Immunol 149(2):650-658.e5; https://doi.org/10.1016/j.jaci.2021.06.025
4. Hendrickx D.M. et al. (2023) Assessment of infant outgrowth of cow's milk allergy in relation to the faecal microbiome and metaproteome. Scientific Reports 13(1):12029; https://doi.org/10.1038/s41598-023-39260-w
5. Hendrickx D.M. et al. (2023) Trackability of proteins from probiotic Bifidobacterium spp. in the gut using metaproteomics. Beneficial Microbes 14(3):269-280; https://doi.org/10.1163/18762891-20220137
6. Hendrickx D.M. et al. (2025) Identification of potential inflammation markers for outgrowth of cow's milk allergy. PLoS One 20(9):e0331462; https://doi.org/10.1371/journal.pone.0331462
7. Zhu P. et al. (2025) Exploring the Fecal Metabolome in Infants With Cow's Milk Allergy: The Distinct Impacts of Cow's Milk Protein Tolerance Acquisition and of Synbiotic Supplementation. Mol Nutr Food Res 69(1):e202400583; https://doi.org/10.1002/mnfr.202400583