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

Abstract

Human milk oligosaccharides (HMOs) are a major component of human milk. They are associated with multiple health benefits and are manufactured on a large scale for their addition to different food products. In this systematic review, we evaluate the health outcomes of published clinical trials involving the supplementation of manufactured HMOs. We screened the PubMed database and Cochrane Library, identifying 26 relevant clinical trials and five publications describing follow-up studies. The clinical trials varied in study populations, including healthy term infants, infants with medical indications, children, and adults. They tested eight different HMO structures individually or as blends in varying doses. All trials included safety and tolerance assessments, and some also assessed growth, stool characteristics, infections, gut microbiome composition, microbial metabolites, and biomarkers. The studies consistently found that HMO supplementation was safe and well tolerated. Infant studies reported a shift in outcomes towards those observed in breastfed infants, including stool characteristics, gut microbiome composition, and intestinal immune markers. Beneficial gut health and immune system effects have also been observed in other populations following HMO supplementation. Further clinical trials are needed to substantiate the effects of HMO supplementation on human health and to understand their structure and dose dependency.

Preterm nutrition and brain development

“…Another class of components studied were HMOs. It has been demonstrated that supplementing infant formula with HMOs (in particular with 2'-FL), the composition and effects of the formula become similar to those of breast milk (better growth, reduced number of respiratory infections, better gut microbiome composition, reduced plasma levels of proinflammatory cytokines), 37 but no clinical study has so far demonstrated a direct effect on neurocognitive development, although this can be presumed from preclinical studies (improved neuronal connectivity, long-term memory and potentiation). 21 Until now, only one study analysed the effect of HMO supplementation on preterm infants: Hascoët et al 38 conducted an RCT which included 86 preterm and VLBW infants (43 received HMO supplement with 2'-FL and lacto-N-neotetraose; 43 received glucose-based placebo) and reported a significant better growth in length and head circumference in the HM group.…”

Safety of 2′‐fucosyllactose (2’‐FL) produced by a derivative strain (Escherichia coli SGR5) of E. coli W (ATCC 9637) as a Novel Food pursuant to Regulation (EU) 2015/2283

“…In a recent publication (Schönknecht et al., 2023), a systematic review evaluated the health outcomes of 26 published clinical trials performed with HiMOs. A total of eight different HiMO alone or in mixtures at different dose levels in comparison with standard IF and/or breastfed infants were evaluated.…”

Human Milk Oligosaccharides, Growth, and Body Composition in Very Preterm Infants

“…However, the findings are variable, and the results are not consistent across all studies. Moreover, formula-randomized controlled trials and real-world studies have not shown added growth benefits among those receiving supplementation with select HMOs [ 25 , 26 , 27 , 28 ].…”