Effects of an Amino Acid-Based Formula Supplemented with Two Human Milk Oligosaccharides on Growth, Tolerability, Safety, and Gut Microbiome in Infants with Cow’s Milk Protein Allergy

Abstract

This open-label, non-randomized, multicenter trial (Registration: NCT 03661736) aimed to assess if an amino acid-based formula (AAF) supplemented with two human milk oligosaccharides (HMO) supports normal growth and is well tolerated in infants with a cow’s milk protein allergy (CMPA). Term infants aged 1–8 months with moderate-to-severe CMPA were enrolled. The study formula was an AAF supplemented with 2′-fucosyllactose (2′-FL) and lacto-N-neotetraose (LNnT). Infants were fed the study formula for 4 months and were offered to remain on the formula until 12 months of age. Tolerance and safety were assessed throughout the trial. Out of 32 infants (mean age 18.6 weeks; 20 (62.5%) male), 29 completed the trial. During the 4-month principal study period, the mean weight-for-age Z score (WAZ) increased from −0.31 at the baseline to +0.28 at the 4-months’ follow-up. Linear and head growth also progressed along the WHO child growth reference, with a similar small upward trend. The formula was well tolerated and had an excellent safety profile. When comparing the microbiome at the baseline to the subsequent visits, there was a significant on-treatment enrichment in HMO-utilizing bifidobacteria, which was associated with a significant increase in fecal short-chain fatty acids. In addition, we observed a significant reduction in the abundance of fecal Proteobacteria, suggesting that the HMO-supplemented study formula partially corrected the gut microbial dysbiosis in infants with CMPA.

Can Human Milk Oligosaccharides Modulate the Allergic Response and Improve the Management of Cow’s Milk Protein Allergy?

“…26 For the final part of her presentation, Nowak-Węgrzyn focused on results of the Platypus study: a single-arm observational trial conducted in Australia that evaluated growth in 32 infants with moderate-to-severe CMPA fed an AAF containing two HMOs: 2'FL (1 g/L) and LNnT (0.5 g/L). 29 The mean age of the study population was 18.6 weeks, with a slight male predominance (62.5%). In terms of clinical manifestations of CMPA at enrolment, the majority of infants had GI or delayed-type skin reactions.…”

“…Eczema/atopic dermatitis was present in 53.1% of infants. 29 Results of the Platypus study showed improvement in growth parameters with HMO-supplemented formula feeding. 29 All anthropometric parameters (i.e., Z-scores for weight, length, head circumference, and BMI) progressed along the World Health Organization (WHO) normal growth curves, with an upward trend from baseline to 4-month follow-up (Figure 2).…”

“…29 Results of the Platypus study showed improvement in growth parameters with HMO-supplemented formula feeding. 29 All anthropometric parameters (i.e., Z-scores for weight, length, head circumference, and BMI) progressed along the World Health Organization (WHO) normal growth curves, with an upward trend from baseline to 4-month follow-up (Figure 2). Nowak-Węgrzyn also noted that there was a "dramatic improvement in symptoms," with infants experiencing a significant reduction in the frequency of presenting CMPA symptoms from enrolment to 1-month follow-up (Figure 2).…”

“…Overall, the study AAF demonstrated an excellent safety profile and was tolerated well by infants with moderate-to-severe CMPA. 29 As with the CINNAMON study, faecal microbiome analysis was also performed as part of the Platypus trial. Results showed an enrichment of the genus Bifidobacterium, with significant changes seen as early as the first month, and maintained to 12 months of age.…”

Microbiome Therapeutics for Food Allergy

“…Notably, dysregulation in the metabolism of lysine, leucine, and threonine have been associated with food allergies [ 106 ]. Emerging evidence suggests that there may be clinical benefits to combining symbiotics with amino acid formulas, and continued studies on amino acid supplementation for promoting beneficial microbial composition will be crucial [ 111 , 112 , 113 ].…”