Human Oligosaccharides

13 min read /
HMO in the nutrition of infants

A mother‘s breast milk is the natural and ideal food for babies. It provides the energy and nutrients that every infant needs in the first 4–6 months of life, in the right quality and quantity. Breastfeeding and the resulting intestinal microbiomes are related to the better health of the infant. HMOs play an important role here.

Many factors such as the length of lactation, environmental and genetic factors influence the amount of HMOs. HMOs can support the development of immune function and provide protection against infectious diseases, directly through the interaction of intestinal epithelial cells or indirectly through the modulation of intestinal microbiota, including the stimulation of
bifidobacteria.

Infants who are breastfed for shorter periods or not breastfed suffer more frequently from infectious diseases such as gastroenteritis and acute middle ear infection, have more immune-mediated diseases, a lower intelligence quotient. And they are likely to have a higher risk of overweight and type 2 diabetes later in life.

Recently it has become possible to produce the first oligosaccharides that are structurally identical to those found in breast milk. It is important that HMOs are resistant to cold and heat and are not affected by pasteurisation and freeze-drying. The addition of an HMO, namely 2‘-fucosyllactose (2‘-FL), is a step forward in bringing artificial infant nutrition closer to the gold standard: breast milk.



No adverse effects have been reported for the addition of an HMO, namely 2‘ fucosyllactose (2‘-FL), and in vitro and animal studies have demonstrated the benefits of supplementing infant formula with 2‘-FL. Lacto-N-neotetraose (LnNT) is also added to the infant formula. A first clinical study with an infant formula (2‘-FL and LNnT) showed that infants fed with the 2‘-FL and LNnT formula were less likely to develop respiratory infections and needed antibiotics less often in the first year of life than those fed the same formula without HMO. From this it can be concluded that 2‘-FL and LNnT are a safe and beneficial supplement to infant formula.

This is especially true for special foods for infants with cow‘s milk allergy (CMA).
Vandenplas Y, DOHaD 2019

Microbiome and neurological development

Pregnancy and the first weeks of life are marked by significant changes in the composition of our body‘s microbiomes. These changes coincide with key periods of infant developmental plasticity.

This leads to a complex dialogue between the brain and the microbes that colonize the gastrointestinal tract. Studies in recent years have shown the existence of a bi-directional microbial gut-brain axis.

The composition of the intestinal microbiome of the pregnant woman is subject
to a dynamic change to support the fetus. This composition is influenced by numerous external factors such as nutrition, medication, lifestyle, but also by infections, hospital stays and stress. Inadequate intake of micro and macronutrients, maternal overweight and high fat content are associated with poor development of the child‘s nervous system. New data indicate that maternal consumption of prebiotics, probiotics and psychotropic drugs affect the stability of the maternal and child‘s microbiome and thus the behavior of the offspring.

The type of delivery affects the infant‘s microbiome only temporarily. Over time, section children develop a microbial population similar to that of infants with vaginal deliveries.

Breastfeeding is obviously an influential parameter compared to bottle feeding. Breast-fed infants have a clear microbial „fingerprint“ in the intestine, they also show improved verbal and non-verbal cognitive skills in childhood compared to the toddlers who received infant formula.
Codagnone MG, Ann Nutr Metab 2019



2’FL promotes cognitive development

Maternal factors, such as breast milk, have been shown to influence the development of a baby. Animal studies have shown that the oligosaccharide 2‘FL contained in breast milk has a positive influence on the development of the nervous system. The first human study confirmed that this 2‘FL found in breast milk promotes cognitive development.

In a cohort study at the Saban Research Institute of Children‘s Hospital Los Angeles with 50 mothers and their babies, the researchers analysed the composition of breast milk and the frequency of feeding at the ages of 1 and 6 months. A special technology makes it possible to link differences in milk composition with specific infant outcomes such as cognitive development. Cognitive development was measured at the age of 24 months using the Bayley III scale. It was shown that the amount of 2‘FL in breast milk in the first month of feeding was associated with significantly higher values of cognitive development in infants at the age of 2 years. Since similar associations were not observed after 6 months, it can be assumed that early exposure to 2‘FL may be most important for the improvement of infant learning and memory, with benefits that may continue into adulthood.



The observations showed that the improved neuronal development induced by breastfeeding is primarily due to mothers producing more 2‘FL for the baby‘s consumption. For women who are unable to breastfeed or can only breastfeed briefly, 2‘FL could be added to the baby‘s diet to support its cognitive development.
Berger PK et al., PLOS ONE, 2020

HMOs influence the risks of a premature birth

Every year around 15 million children are born too early. Premature
birth is one of the main causes of new-born mortality. The causes
of spontaneous preterm birth (PTB) are multifactorial and often
unknown. The study tested the hypothesis that human milk oligosaccharides
(HMOs) in blood and urine modulate the maternal urinary and vaginal microbiome and influence the risk for PTB.

The vaginal and urinary microbiome of a cross-sectional cohort of women with and without preterm labour was analysed and correlated with measurements of metabolites and HMO in urine and blood. Several microbial signatures associated with the short cervix, PTB and/or preterm contractions were identified, e.g. Lactobacillus jensenii, L. gasseri, Urea-plasma sp. and Gardnerella sp. In addition, associations between sialylated HMO, especially 3‘-sialylylactose, with PTB, short cervix and increased inflammation were shown. They confirmed an influence of HMO on the microbiome profile. In the identification of serum and urine HMOs and several key chemical organisms associated with PTB, the results indicate two different processes which influence the risk for PTB.

One process appears to be driven by sterile inflammation characterised
by elevated serum concentrations of sialysed HMO.

A second process could be microbially mediated, possibly driven by
secretor-active HMOs in urine.
Pausan M-R et al., bioRxiv 2019