Human milk oligosaccharides (HMOs) are a major component of human milk, associated with multiple health benefits including shaping a healthy infant gut microbiome, possibly supporting brain development and the maintenance of a well-balanced immune system, reducing the risk of bacterial imbalance and maturing and maintaining the integrity of the intestine.
The new review includes 26 published relevant clinical trials and five publications describing follow-up studies from the PubMed database and Cochrane Library. The clinical trials tested eight different HMO structures individually or as blends in varying dosages.
The authors say this is the first systematic review covering the use of manufactured HMOs as food supplements in humans.
"Here, we provide a comprehensive overview of clinical studies conducted in populations of all ages that have supplemented manufactured HMOs to different food products and summarize the evidence on health outcomes and the current state of clinical research."
The paper outlines articles published until the end of 2022. All studies reported safety and tolerance of the respective single HMO and HMO blends, the HMOs applied differed in complexity and dosage.
Several studies reported a positive shift in outcomes towards those observed in breastfed infants - including stool characteristics, gut microbiome composition, intestinal immune markers, and beneficial effects on gut health and the immune system.
Beneficial gut health and immune system effects have also been observed in other populations following HMO supplementation.
Focus on strengthening scientific insights and expertise
Most of the clinical trials indicated changes in the gut-associated microbiome with HMO supplementation. The selective consumption of HMOs by species of Bifidobacterium, Bacteroides, and Lactobacillus provides them with a growth advantage. In children and adults, HMO supplementation increased the abundance of bifidobacteria, although the physiological relevance of this modulatory effect is unclear.
HMO administration was associated with additional gut health outcomes that may be linked to the metabolic activity of the bacterial communities dominating the gut, including increased faecal content of SCFAs, reduced faecal pH, and modulation of microbial metabolic pathways. HMO supplementation also promoted more frequent and softer stools. Two studies reported changes in stool characteristics along with microbiome changes.
Changes in the microbiome may also be associated with a reduced number of infections. Infants receiving HMO supplements suffered from less-frequent respiratory tract infections, were less likely to need attention from health professionals, and were less likely to experience otitis media.
Associations between faecal communities rich in bifidobacteria, microbial metabolic pathways, and reduced infections have been reported.
These outcomes may be mediated by a combination of mechanisms. In a Bifidobacterium-dominated gut environment, the growth of pathogenic bacteria is strongly discouraged. The microbiome may also support the immune system, either by direct interaction with immune cells or by producing immunomodulatory metabolites.
The authors assert that further evidence from well-designed clinical trials and preclinical experiments is required to substantiate the evidence for health benefits in different populations.
Dr. Katja Parschat, Head of Research & Development, Chr. Hansen HMO, says “At Chr. Hansen, we continuously create research and clinical trials to further explore the effects of HMO supplementation on human health and to understand the structure and dose dependency of HMOs. It is a strategic priority for us to invest in building in-depth knowledge in this emerging field and provide insights on the benefits of HMOs.
“Our aim is to support the healthy development of infants that cannot be breastfed by providing HMOs as an ingredient for infant formula. With the publication of the in-depth systematic review, Chr. Hansen contributes to building knowledge on the beneficial effects of HMO, assessing the current study level. We are happy to provide this to customers and researchers to facilitate and to collaborate on further insight building around HMOs,” she concludes.
"Clinical Studies on the Supplementation of Manufactured Human Milk Oligosaccharides: A Systematic Review"
Schönknecht, Y.B.; Moreno Tovar, M.V.; Jensen, S.R.; Parschat, K.