Investigating the impact of cow’s milk allergy interventions on infants’ gut microbiomes

Title: Investigating the impact of cow’s milk allergy interventions on infants’ gut microbiomes

Given that cow’s milk allergy (CMA) is one of the most prevalent allergies in early childhood, it is vital that we develop a deeper scientific understanding of the effects of dietary interventions on the gut microbiome – so that we can support infants with CMA and help them (and their gut flora) to thrive. To find out more, our scientists went looking for answers in some critical material: baby poo.

The study, which has now been published in the peer-reviewed journal Molecular Nutrition & Food Research,¹Pingping Zhu, Mariyana V. Savova, Alida Kindt,
the PRESTO study team, Harm Wopereis, Clara Belzer,
Amy C. Harms,Thomas Hankemeier​. DOI: 10.1002/mnfr.202400583.R2​ . examined the impact of giving synbiotic supplements to infants with CMA. Synbiotics are mixtures of probiotics and prebiotics designed to support digestion, containing both ‘good’ bacteria and fibers to help those bacteria grow.

The scientists’ research, which was part-funded by Danone Research & Innovation (R&I) via the EARLYFIT project, revealed that six months of synbiotic supplementation did successfully – and significantly – alter the infants’ fecal metabolome (the complete set of small-molecule chemicals within their poo).

Harm Wopereis, a senior scientist at Danone R&I, is one of the co-authors of the paper. “With cow’s milk allergy in infants,” he explains, “we’re understanding more and more about the relevance of the gut microbiome – and this study showed some intriguing results. With a stronger evidence base, we can ensure infants get the right support and treatment.”

Finding answers in feces 

CMA affects approximately 0.5–3% of children in developed countries, ²J. D. Flom and S. H. Sicherer /. “Epidemiology of Cow’s Milk Allergy,” Nutrients 11 (2019): 1051.; Høst, “Frequency of Cow’s Milk Allergy in Childhood,” Annals of Allergy, Asthma … Continue reading making it one of the most prevalent food allergies in early childhood and creating dietary challenges for infants and their families. This study focused on infants with immunoglobin E (IgE)-mediated CMA, the most common form of food allergy.

The study’s authors analyzed a subset of stool samples collected during PRESTO – a multicenter, randomized, double-blind, controlled clinical study – as part of EARLYFIT, a project to identify molecular markers that underlie the interaction between nutrition, the intestinal microbiome, and immune fitness in early life.​

The EARLYFIT project was part of the partnership program between NWO Domain Applied and Engineering Sciences (AES) and Danone Research & Innovation (R&I). The project focused on the development and understanding of new concepts for specialized nutrition that influence the immune fitness, special baby and toddler nutrition, and medical nutrition. It brought together scientists from three Dutch universities: Wageningen University, Radboud UMC Nijmegen and Leiden University.

In the clinical trial, CMA-allergic infants all received amino acid-based formula (AAF), but some also received synbiotic supplementation containing inulin, oligofructose, and Bifidobacterium breve M-16V. Their feces were sampled at the start of the trial, and then after six and 12 months.

Digesting the results 

The analysis revealed that synbiotic intake altered the infants’ levels of purine, bile acid, and unsaturated fatty acids. There were also indications of successful colonization by ‘good’ bacteria: while children with IgE-mediated CMA may have less bifidobacteria than their healthy counterparts,³M. V. Savova, P. Zhu, A. C. Harms, R. G. van der Molen, C. Belzer, and D. M. Hendrickx, “Current Insights Into Cow’s Milk Allergy in Children: Microbiome, Metabolome, and Immune Response—A … Continue reading these results suggest induced bifidobacteria activity among those taking synbiotic supplements.

“At the six-month mark, we ​found increased metabolites produced by infant-type Bifidobacterium species enhanced by the synbiotic formula: indolelactic acid and 4-hydroxyphenyllactic acid,” says Harm. “The increase subsequently declined after 12 months of intervention, but this is a significant finding. Bifidobacteria and its metabolites play a pivotal role in gut microbiome development in early life.”

The study also looked at the impact of cow’s milk tolerance acquisition – i.e., when infants outgrow their allergy – on the fecal metabolome. The results were inconclusive, but the analysis did suggest that amino acids, bile acids, and branched short-chain fatty acids were more present in infants who outgrew CMA, compared to those with more persistent CMA​.

“EARLYFIT has been an extremely valuable project,” says Guus Roeselers, Senior Team Leader in Gut Microbiology & Specialized Nutrition at Danone R&I. “Together, these experts were able to collect and analyze evidence that will ultimately have a real-world impact for parents and their babies in those critical early months.”