The expanding universe of HMOs: From early life nutrition to innovative adult health applications

Human milk oligosaccharides (HMOs) have long been sought out for their proven health benefits and efficacy, particularly in the realm of infant and early life nutrition and gut health. Yet, as the science surrounding HMOs as well as research in the gut axes, continues to broaden, so do the applications for these innovative ingredients.

Nutrition Insight sits down with experts from dsm-firmenich and Novonesis to better understand the evolving HMO space.

According to Thomas Stenfeldt Batchelor, SVP, advanced health and protein solutions at Novonesis, HMOs, which are prominent in breast milk, are primarily utilized in infant formula. 

However, their use is expanding beyond formula to encompass young children’s milk and complementary foods like cereals. This shift is driven by the critical importance of the first 1,000 days of a child’s life and ongoing research on the health benefits of HMOs for toddlers.

“More and more research focuses on the use of HMOs in adult supplements with interest in specific health indications, such as irritable bowel syndrome (IBS),” Batchelor explains. “However, even more research is indicating that HMOs are supportive for inflammatory disorders, such as atherosclerosis, which is currently being investigated clinically.”

Marta Mikš, the senior regulatory and scientific affairs manager at dsm-firmenich, agrees and notes that, in addition to infant health and adult nutrition, dsm-firmenich is exploring new applications in areas such as skin care, though she emphasizes that it is too early to disclose any findings at this stage.

“We see an increased demand across the globe as HMO penetration is increasing,” says Mikš. “Average penetration in infant formula is only at 10%, so it is important that more babies get access to the health benefits of this critical component of breast milk whenever breastfeeding is not possible.”

“The Chinese market is still limited by regulatory boundaries and is about to open up for products targeting infants and children below three years. This will lead to a steep increase in demand from that region.”

An expanding market

Innova Market Insights’ data suggests a 16% increase in the use of HMO ingredients in baby and toddler products from July 2019 to June 2024, predominantly in baby formula. At the same time, the application of HMOs is broadening to include new product developments in supplements.

Batchelor reveals that one of the main factors for HMOs rapidly gaining traction in infant formula is their close similarity to breast milk, being the third most abundant solid component. Moreover, he states that consumer research indicates growing awareness and preference among parents for products containing HMOs, especially when seeking alternatives closest to breast milk for their children.

“Novonesis has long-term expertise and experience in producing HMOs,” says Batchelor. “Our HMOs are produced via fermentation and subsequently purified in a process where the HMOs are separated from the microbial production strain.”

“Finally, the HMOs are spray-dried to create a fine-grade powder as the final product. This unique process results in superior sensory properties, such as taste and smell.”

Novel ingredients

Mikš highlights that HMOs are stable and manageable in both production and application. The primary challenge is their high production cost, but efforts are underway to reduce expenses and expand their inclusion in more finished products.

“dsm-firmenich is the only HMO supplier with authorizations encompassing eight unique HMO structures in a growing number of markets, including the EU, US and UK,” she underscores.

She adds that this includes: 

• Four neutral fucosylated HMOs — 2’-fucosyllactose (2’-FL), difucosyllactose (DiFL), 3-fucosyllactose (3-FL) and lacto-N-fucopentaose I.
• Two neutral core HMOs — lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT).
• Two acidic sialylated HMOs — 6’-sialyllactose (6’-SL) and 3’-sialyllactose (3’-SL) sodium salts. 

“The diversity of these HMO structures translates into unique biological functions. Depending on the food application, these HMOs can be formulated individually or in combinations with other ingredients such as probiotics.”

Batchelor spotlights that all currently marketed HMOs are produced via microbial fermentation.

“In nature, there are more than 150 HMOs present in breast milk that are known to date. Commercialized are currently HMOs such as fucosylated 2’-FL, 3-FL and DiFL, sialylated lactose 3’-SL, 6’-SL as well as LNT and LNnT,” he illustrates. “These HMO structures are relatively simple because they are small in size and either fucosylated or sialylated in only one position.” 

“Future HMOs are more complex because they are in their chemical structure increasing in size and complexity by being modified several times by fucosylation or sialylation.”

The future of HMOs

Batchelor reveals that the future of HMOs hinges on science and clinically proven benefits, such as the clinical study conducted on its MyOli5 HMO Mix. Additionally, Novonesis recently conducted a clinical study in collaboration with Aarhus University, Denmark’s Technical University, and Copenhagen University to evaluate short- and long-term health outcomes in conjunction with HMO supplementation.

“Our study delves into the mechanism of action of HMOs, alongside analyzing microbial metabolites to understand the impact of microbiome changes as well as effects of HMOs on immune system maturation,” he explains. “These efforts underline our strong commitment to enhancing the understanding and efficacy of HMOs in promoting infant well-being.”

hhe also states that she anticipates that synbiotics — combinations of HMOs and probiotics — and special and medical nutrition applications will be a future trend as science continues to unveil how HMOs can address specific health challenges across all demographics.

At the same time, Mikš highlights that research into HMOs is constantly advancing, leading to more precise nutrition solutions that better mimic breast milk for formula-fed infants. She also notes that scientists are exploring the distinct roles of various HMOs and their combinations to determine the most effective compositions and dosages for optimal health benefits.

“This understanding will be crucial in enhancing infant formula formulations to better support infant growth and development,” she emphasizes. “Furthermore, the potential synergies between HMOs and other bioactive ingredients, particularly probiotics, are being actively investigated and these combinations, known as synergistic synbiotics, offer enhanced health benefits aiming to improve gut and immune health and potentially contribute to mental and metabolic well-being.”

“Finally, advances in biotechnology and fermentation processes are also making it possible to produce more complex and diverse HMO structures on a commercial scale, which can more closely replicate the diversity of oligosaccharides found in human breast milk and associated benefits,” Mikš concludes.