The promise of human milk oligosaccharides

MANY studies show how human milk oligosaccharides (HMOs) can strengthen the human immune system as early as infancy.

HMOs are complex sugar molecules that support the immune system and inhibit pathogen. They add to the nourishing quality of breast milk which naturally contains lactose, lipids, proteins, vitamins, mineral nutrients, hormones and antibodies.

Constituting the third largest component of breast milk after lactose and fats, HMOs are unique to humans in concentration and structural diversity. Being anti-pathogenic, they are an ideal ingredient to add in infant formula, adult nutrition such as dairy products, cereals and beverages. Their benefits extend to pharmaceutical and dermatological applications as well.

Biotech company, Jennewein's  5‑HMO blend is closer to natural breast milk as it is a combination of five of the most common HMOs in nature-identical concentrations.

HMOs act as prebiotics

Over the last decade, bodies of scientific research suggest the positive effects of HMOs on infant immune system and brain development. Findings also point to reduced risk of necrotising enterocolitis, the most common and fatal disorder in preterm neonates.

Acting as prebiotic, HMOs promote the growth of beneficial bacteria and aids the development of infant microbiome. A natural and healthy microbiome helps the overall development of an infant. Failure to support it reportedly leads to obesity, autism, allergy, and other issues related to infant health and development.

Some 200 different HMO structures have been identified and can be assigned to three classes, according to Dr. Katja Parschat, deputy head of R&D at Jennewein Biotechnologie, an international biotech company based in Germany.  

The neutral HMOs, such as lacto-N-tetraose are prebiotic, stimulating the growth of commensal bacteria such as bifidobacteria and lactobacilli.

Fucosylated HMOs, such as 2’-Fucosyllactose (2’-FL) and 3‑Fucosyllactose (3’-FL), not only support the growth of friendly bacteria; they also protect against infectious diseases by inhibiting the adhesion of viruses and pathogenic bacteria to receptors on human target cells.

Sialylated HMOs, such as 3’-sialyllactose and 6’‑sialyllactose are major sources of sialic acid, a versatile molecule required for proper brain development during the first months of life.

Each of these chemically diverse sugars confers different beneficial effects on developing infants. This is why breast milk is so important to infants. So, when mothers are unable to breastfeed, their babies lose a considerable amount of natural healthy components.

“As an alternative, they can use formula, which is enriched with HMOs such as the 2’-FL,” says Dr. Bettina Gutiérrez, head of press and public relations at Jennewein.

The 2’-FL is the most common HMO, existing in around 80% of all human milk samples at a concentration of 3g/L.

Large-scale production of HMOs

Jennewein has succeeded in producing 2’-FL and other HMOs at an industrial scale using its in-house fermentation technique. “This process has the E-Coli B21 bacterial strain as a base,” reveals Dr. Gutiérrez. “This strain is genetically engineered so that the bacteria can produce the enzymes necessary for production.”

The 2’-FL approved for infant and toddler nutrition has a generally regarded as safe (GRAS) status from the US Food and Drug Administration, and registered as a Novel Food in the European Union.

The concentration of HMOs currently added to infant formula varies between 0.2 and 1.5 g/L, but 2’-FL is approved with a maximum concentration of 3g/L. The Lacto-N-neotetraose at a concentration of 0.6 g/L can be combined with 1.2 g/L 2’‑FL to achieve a total HMO concentration of 1.8 g/L, as stipulated by the European Union list of Novel Foods.

5‑HMO blend

Jennewein’s 5‑HMO blend is closer to natural breast milk as it is a combination of five of the most common HMOs in nature-identical concentrations: 2’-FL, 3’-FL, lacto-N-tetraose, 3’-sialyllactose and 6’-sialyllactose,” reveals Dr. Gutiérrez. “This means that this new blend is the first product to contain both acidic and neutral HMOs.”

All the HMOs in this blend are anti-infective, able to protect against a variety of pathogens including Campylobacter jejuni (2'-FL), Salmonella (2'-FL, 3-FL), Streptococci (LNT) and noroviruses (2’-FL, 3-FL, 3’-SL and 6’-SL), says Dr. Gutiérrez.

“They also help to enhance the natural gut microbiome by promoting the growth of beneficial bacteria such as Bifidobacteria, Lactobacilli and Bacteroides. The fucosylated and sialysed HMOs 2’-FL, 3’-FL, 3’-SL and 6’-SL are immunoregulated. In addition, the 3’-SL and 6’-SL oligosaccharides support brain development in infants by providing sialic acid, which is an important component for neurons,” she adds.

The company hopes to market 5‑HMO in autumn of this year.

GOS and FOS soon out

According to Dr. Parschat, “the broad panel of HMOs extends the spectrum of positive effects for developing infants. By ensuring that the concentration of HMOs is similar to natural versions, the carbohydrate content of infant formula is becoming increasingly similar to that of natural breastmilk. This may make the addition of artificial prebiotics such as GOS and FOS unnecessary in the future.”

To ensure that the 5’-HMO mix is well tolerated and safe for infants, the company has been conducting a clinical study since 2018 in hospitals in Italy, Spain and Germany. This study involves 324 babies who have been divided into three groups.

“The first group received baby food with the HMO preparation, the second was fed a reference formula and the third was breastfed,” explains Dr. Gutiérrez. “Subjects were successfully recruited from all three countries. To date, good compatibility with the food supplemented with the 5'-HMO mix has been found in infants. The study is expected to be completed in autumn, with the product launched in Europe soon after.

Venture in Asia

Given such benefits and developments in HMOs, one would assume that HMOs are being widely used in infant milk formulas. But Jennewein Biotechnologie says that is not yet the case. The company, however, is committed to increasing the adoption of HMOs not only in Europe but also in Asia and other parts of the globe.

Already, the company has received approval for its 2’-FL in Singapore and has initiated the process for the approval of its HMOs in China, which accounts for the largest market share of baby food.

Recently Jennewein signed a Memorandum of Understanding on infant microbiome and human milk oligosaccharides, with Inner Mongolia Yili Industrial Group (Yili Group), China’s leading dairy company to develop an innovative infant formula and dairy products specifically tailored to the Chinese market.

In a press release, Dr. Gerrit Smit, managing director of Yili Innovation Center Europe, said: “Yili Group has been dedicated to Chinese breast milk composition studies for years and has initiated the establishment of a Chinese Breast Milk Database. “Yili has constantly brought innovative products to the market based on scientific research, for example Pro-Kido, and is looking forward to collaborating with Jennewein in the future.”

Furthermore, the HMOs from Jennewein Biotechnologie are kosher and halal, and this increases their opportunities in a wider market.