An Extensively Hydrolyzed Formula Supplemented with Two Human Milk Oligosaccharides Modifies the Fecal Microbiome and Metabolome in Infants with Cow’s Milk Protein Allergy

Abstract

Cow’s milk protein allergy (CMPA) is a prevalent food allergy among infants and young children. We conducted a randomized, multicenter intervention study involving 194 non-breastfed infants with CMPA until 12 months of age (clinical trial registration: NCT03085134). One exploratory objective was to assess the effects of a whey-based extensively hydrolyzed formula (EHF) supplemented with 2′-fucosyllactose (2′-FL) and lacto-N-neotetraose (LNnT) on the fecal microbiome and metabolome in this population. Thus, fecal samples were collected at baseline, 1 and 3 months from enrollment, as well as at 12 months of age. Human milk oligosaccharides (HMO) supplementation led to the enrichment of bifidobacteria in the gut microbiome and delayed the shift of the microbiome composition toward an adult-like pattern. We identified specific HMO-mediated changes in fecal amino acid degradation and bile acid conjugation, particularly in infants commencing the HMO-supplemented formula before the age of three months. Thus, HMO supplementation partially corrected the dysbiosis commonly observed in infants with CMPA. Further investigation is necessary to determine the clinical significance of these findings in terms of a reduced incidence of respiratory infections and other potential health benefits.

Clinical Studies on the Supplementation of Manufactured Human Milk Oligosaccharides: A Systematic Review

“…At the time of writing, ten additional clinical trials were registered as ongoing in the ClinicalTrials.gov database, investigating HMOs as preventives or therapeutics (clinicaltrials.gov, accessed on 26 July 2023). In the time between the literature search and the preparation of this review, four clinical trial follow-up studies were published focusing on the effects of HMOs on the microbiome [89][90][91] or microbiomederived markers [92]. This reflects that clinical HMO research is a rapidly evolving field with potential new insights to come out in the future.…”

Probiotics in the New Era of Human Milk Oligosaccharides (HMOs): HMO Utilization and Beneficial Effects of Bifidobacterium longum subsp. infantis M-63 on Infant Health

“…Apart from B. infantis, HMOs have already been shown to be effective in positively shaping the microbiota of infant gut, which is especially important for the formula-fed infants. The gut microbiota of formula-fed infants are often characterized by a higher degree of microbial diversity, lower abundance of bifidobacteria and higher count of pathogens than breastfed infants, all of which are shown to be improved to some extent by the supplementation of different HMO mixtures in the formula, as substantiated in recent clinical studies [81,85,86].…”

“…The safety of these HMOs is supported in clinical trials, with the addition level ranging from 0.2 g/L to 5.75 g/L. The efficacy of HMO supplementation in modulating gut microbiota composition and mediating the immune response have also been studied [79][80][81][82][83]. Collectively, these human clinical studies propel the regulatory approvals for the use of HMOs in infant formula in different countries.…”

Prebiotics in New-Born and Children’s Health

“…The nutritional makeup of human milk is replicated as precisely as possible in infant formula, which is designed specifically for babies. Most baby formulae are either made from cow milk or soy milk, and their goal is to mimic the nutrient profile of human breastmilk [77,78]. Prebiotics in infant formula are modeled after the prebiotic oligosaccharides found in human milk.…”