Infant Formula Supplemented with Five Human Milk Oligosaccharides Shifts the Fecal Microbiome of Formula-Fed Infants Closer to That of Breastfed Infants

Abstract

Breastmilk is the optimal source of infant nutrition, with short-term and long-term health benefits. Some of these benefits are mediated by human milk oligosaccharides (HMOs), a unique group of carbohydrates representing the third most abundant solid component of human milk. We performed the first clinical study on infant formula supplemented with five different HMOs (5HMO-mix), comprising 2′-fucosyllactose, 3-fucosyllactose, lacto-N-tetraose, 3′-sialyllactose and 6′-sialyllactose at a natural total concentration of 5.75 g/L, and here report the analysis of the infant fecal microbiome. We found an increase in the relative abundance of bifidobacteria in the 5HMO-mix cohort compared with the formula-fed control, specifically affecting bifidobacteria that can produce aromatic lactic acids. 5HMO-mix influenced the microbial composition as early as Week 1, and the observed changes persisted to at least Week 16, including a relative decrease in species with opportunistic pathogenic strains down to the level observed in breastfed infants during the first 4 weeks. We further analyzed the functional potential of the microbiome and observed features shared between 5HMO-mix-supplemented and breastfed infants, such as a relative enrichment in mucus and tyrosine degradation, with the latter possibly being linked to the aromatic lactic acids. The 5HMO-mix supplement, therefore, shifts the infant fecal microbiome closer to that of breastfed infants.

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.…”

The Role of Diet and Nutritional Interventions for the Infant Gut Microbiome

“…Efforts to promote the development of a gut microbiome in FF infants that closely resembles that of a breastfed infant in order to emulate health advantages conferred by breast milk include the supplementation of infant formula with prebiotics, probiotics or symbiotics [106][107][108], which are synergistic combinations of both.…”

“…Although infant formula products are engineered to replicate the macronutrient profile of human milk, currently, the majority of them do not incorporate substantial levels of prebiotics and/or probiotics, as reported by Salminen et al in 2020 [113]. Babies fed with formula enhanced with HMOs exhibited increased Bifidobacteria and decreased Enterobacteriaceae and Peptostreptococcaceae [107]. A study by Borewicz [99] compared the fecal microbiota composition in infants who were breastfed with that of babies fed with an infant formula fortified with prebiotics (GOS and/or FOS) or receiving mixed feeding.…”

Human milk oligosaccharides differentially support gut barrier integrity and enhance Th1 and Th17 cell effector responses in vitro

“…More than 150 structurally distinct HMOs have been identified, which are generally divided into three structural groups: neutral fucosylated, neutral non-fucosylated, and acidic (sialylated) HMOs ( 1 ). HMOs benefit infant health by modulating the gut microbiome ( 2 – 4 ), strengthening intestinal barrier integrity and function ( 5 , 6 ), immunomodulation ( 7 , 8 ), and supporting cognitive development ( 9 , 10 ). Most HMOs are undigested when they reach the lower gut, where they are fermented by the intestinal microbiome ( 11 ).…”