Tip of the iceberg: Vast opportunities for developing pre/probiotics/synbiotics with HMOs – Biostime event
HMOs could serve as prebiotic for beneficial bacteria to utilise, said Dr Lars Bode, Professor of Paediatrics in the Division of Neonatology and the Division of Gastroenterology, Hepatology and Nutrition, at the University of California, San Diego.
Prof Bode is also the Larsson-Rosenquist Chair of Collaborative Human Milk Research, and Director of the Larsson-Rosenquist Foundation Mother-Milk-Infant Centre of Research Excellence (MOMI CORE) at the university.
He was speaking at the Biostime Nutrition Professional Webinar Series organised by Biostime Institute Nutrition and Care (BINC). Biostime is also an infant nutrition brand under China firm Health and Happiness Group (H&H Group).
Well-known HMOs include 2’FL and 3’FL. Studies have shown that different probiotics “feed on” different types of HMOs for growth and gut colonisation.
This means that new pre/probiotics could be developed depending on the types of HMOs that they feed on.
For instance, the HMO known as DSLNT is key for preventing necrotizing enterocolitis in pre-term infants. This means that when a probiotic is being developed for preterm babies, the probiotic should not “feed on” DSLNT so that it could be used for preventing necrotizing enterocolitis.
On the other hand, HMOs being temperature and pH stable, are able to survive stomach acid and pasteurisation, again, making it a candidate for new pre/probiotic product development.
“There is opportunity to develop pre/probiotics/synbiotics that specifically go after individual oligosaccharide and leave others intact,” he said.
He explained that this is because different HMOs have different health benefits, hence, developing a probiotics that utilise all HMOs would not be beneficial.
“HMOs are more than just foods for bugs, we know that they have anti-microbial properties, not only do they foster the growth of beneficial bacteria, they also suppress the growth of bacteria that we don’t want.
“We want to keep some oligosaccharides active and intact to do the other wonderful things, for example, as antiadhesives and antimicrobials to prevent pathogens from attaching or stop growing,” he said.
Other functions of HMOs include serving as epithelial cells and immune cell modulators.
While HMOs are more commonly applied in infant formula, there is ongoing research on how it could be used for different functions, beyond infant nutrition.
The following is a list of existing research on HMOs and its potential benefits.Necrotizing enterocolitis
A particular HMO, the DSLNT, has been shown to reduce the risk of necrotizing enterocolitis (NE) in preterm infants.
In preterm infants affected with the disease, drinking HMOs from breast milk could increase survival rates. Those who took infant formula with added HMOs also had a higher survival rate, according to a study by Autran CA et al published in GUT in 2018.
“It is one specific oligosaccharide call DSLNT that is responsible, so it is that one specific oligosaccharide which is associated with lower NEC risk,” Prof Bode said.
This was also proven in animal model study and the evidence provided opportunities to develop newer therapeutics and the opportunity to screen mums and donor milk to provide suitable human milk to infants at risk.Diarrhoea and infection
Existing research has shown that the HMO, 2’FL could reduce the growth of pathogens.
This include campylobacter, enteropathogenic E. coli, and enterotoxic E. coli, according to a WCPGHAN 2020 abstract by Alliet P et al.
The HMO LNT, on the other hand, works on Group B streptococcus (GBS), while 3’SL and 6’SL have applications for protection from rotavirus.Infant growth
Again, 2’FL is a key HMO associated with growth in infancy and early childhood.
In contrast, the HMO LNnT is negatively associated with growth.
As for 3’SL and 6’SL, they are associated with growth in children with malnutrition.Immunity
Certain HMOs are associated with immune functions.
For instance, DFLac (DFL) is associated with cytokine release.
“In cohort studies, we found that it is not individual oligosaccharide that is associated [with a particular condition]. For example, cow milk allergy, food sensitisation, or allergic disease have a mixture of different oligosaccharides associated with it,” said Prof Bode.Cognition
In terms of cognitive development, 2’FL has been shown to exert effects on memory and learning in animal models.
In human cohort studies, it has shown effects on cognitive development at the first 24 months of life.
On the other hand, 3’SL and 6’SL are also associated with memory and learning, according to a study by Wang B published in Advances in Nutrition in 2012.
Other ongoing research will look at HMOs and its impact on obesity, sepsis, and cardiovascular health.
“We strongly believe that we have only seen the tip of the iceberg, there is a lot of room for discovery with 150 to 200 different oligosaccharides, that’s 150 to 200 different opportunities,” said Prof Bode.
What are HMOs?
- HMOs are complex sugars
- HMOs are the third most abundant solid component of human milk, after lactose and lipids
- There are five building blocks for HMOs. Different structures form different oligosaccharides and different structures meant different functions
- HMOs are not a recent discovery, between 150 to 200 oligosaccharides have been identified
- Beside isolating it from humans, it can also be synthetically made bio-engineered from yeast
- There is a higher level of oligosaccharides in human breast milk as compared to bovine milk. The former has about 5-15g/L while the latter has 0.05g/L of oligosaccharides.
- Human breast milk and bovine milk also differ in the types and composition of oligosaccharides. For instance, 2’FL is present in human breast milk but absence in bovine milk.
- Even amongst humans, there are differences in the types and concentration ofligosaccharides, which is akin to a “thumbprint”.
- The concentrate of HMOs in one person will change throughout the weeks and months but is relatively constant throughout the hour and day
- Women who have more kids have a higher level of oligosaccharides in their breast milk and this is independent of their age and child delivery methods (vaginal birth or c-sec)