Research & Education

Human Milk Oligosaccharides Support Infant Immune System Development

The human gut microbiome plays a significant role in immune health and disease prevention in ways that researchers are just starting to identify. Some of the symbiotic interaction between humans and microbes may begin in utero, where the major creation of the human microbiome takes place during birth and early infancy. Breastfeeding plays a significant part in developing the microbiome and infant immune system, with human milk oligosaccharides playing a major role.

Human breast milk contains many key components of which human milk oligosaccharides (HMOs) are the third-most prevalent behind lactose and lipids. There are more than 200 HMOs, all of which contain lactose along with monosaccharides, such as glucose, galactose, or their derivatives. The composition of HMOs in an individual depends on different factors, including genetics, and this follows similar patterns just like blood types. The concentration of HMOs declines over the course of lactation, with colostrum containing the most.

HMOs and the Infant Immune System

HMOs aid in developing the infant immune system, with much of their action being involved in building a healthy microbiome. Human enzymes do not break down HMOs, which is similar to many other oligosaccharides. Instead, these oligosaccharides act as fuel for bacteria and stimulate the growth of a balanced microbiota with higher numbers of commensal bacteria, such as those in the Bacteroides and Bifidobacterium species compared with pathogenic varieties.

In addition to acting as a prebiotic, HMOs also bolster the infant immune system by:

  • Preventing microbes from adhering to the intestinal mucosa because of the structural similarities to the glycoconjugates microbes used to adhere to cells

  • Limiting the growth of pathogens by producing organic acids and bacteriocins

  • Acting as fuel for microbes to produce the short-chain fatty acids (butyrate, propionate, and acetate)

  • Boosting cell maturation in the intestinal mucosa and aiding in barrier function

  • Reducing inflammation by inhibiting gene expression for inflammatory cytokines, chemokines, and receptors

Although much of the action of HMOs occurs in the gastrointestinal tract, studies show that at least 1% of HMOs enter systemic circulation to modulate immune responses. This includes the formation of platelet-neutrophil complexes and binding endothelial cells to immune cells.

The Benefits of Adding HMOs to Formula

Building the infant’s microbiome and immune system relies on more than one player. HMOs have a significant role that may impart similar benefits by adding this supplement to formula.

In a randomized control trial, one group of infants took a formula supplemented with HMOs, and the other group took a control formula for 119 days. The HMO group displayed similar inflammatory cytokine profiles to breastfed infants, both of which were significantly lower (29% to 83%) than those infants consuming the control formula. 

Another study found that infants on an HMO-supplemented formula for the first 6 months of life experienced fewer lower respiratory tract infections in their first year and used less medication than those with traditional formula. In another study, it was found that consuming HMO-supplemented formula led to a microbiome much closer to that of breastfed infants at 3 months of age.

Adding HMOs to formula may aid in building a healthy microbiome. HMO supplementation also supports the development of the immune response in the gut and gut-associated lymphoid tissue. This may help protect infants and facilitate the foundation of a healthier immune response and microbiome as the infant matures into childhood and even into adulthood.

By Kendra Whitmire, MS, CNS