HMOs: Hail to the Chief

Human milk oligosaccharides (HMOs) are the third must abundant solid component in human milk behind #1-lactose and #2-lipids (fats). So far scientists have identified more than 200 of them in human milk. I use the acronym, PIDEN Seal, as a way to remember what HMOs do. This works for me because PIDEN sounds like BIDEN. You may have heard of him.

Six Definitions

1. Oligo means many
2. Mono means one
3. Saccharide means sugar
4. A sugar is a carbohydrate
5. A monosaccharide is a single-unit sugar
6. An oligosaccharide is a sugar made up of many sugars. Oligosaccharides are made up of 2-10 monosaccharide units linked via glycosidic bonds.

 HMO Fun Facts

• Human milk oligosaccharides (HMOs) are made up of differing amounts and configurations of 5 monosaccharides: glucose, galactose, N-acetylglucosamine, fucose, and sialic acid which is usually in the form of N-acetylneuraminic acid.
• As all HMOs have lactose as a building block, it is thought that they are an extension of lactose synthesis, which occurs in the lactocyte, the milk making cell in the breast.
• The types of HMOs in a mother’s milk appear to be genetically determined. Each mother makes a different set of oligosaccharides.
• The quantity of HMOs in human milk varies with the stage of lactation.

As HMOs are a type of carbohydrate, it would be logical to assume that they provide the infant with energy. However, this is not the case. Scientists discovered that human infants actually are unable to digest most of the HMOs. HMOs pass intact and undigested through the stomach and small intestine and end up in the large intestine where most bacteria in the gut microbiome are found.

PIDEN Seal

What do HMOs do? Using the acronym, PIDEN Seal, they:

• P – Prebiotic / Serve as a prebiotic. They help shape a healthy microbiome by encouraging the growth of “good bacteria,” especially Bifidobacteria. This explains the finding that the stool of breastfed babies contains more Bifidobacteria than the stool of formula-fed babies. One type of Bifidobacteria, infantis, has a particular affinity for the HMOs in breast milk.
• I – Immune / Help promote the development of the immune system by shaping the microbiome.
• D – Decoy / Serve as decoy receptors. They fake out the bad guys - the pathogens (viruses, bacteria, parasites) - attracting them to attach to the HMO instead of attaching to gut mucosal surfaces. The HMO + dangerous pathogens package is then excreted in the stool. Examples of pathogens that can bind to HMOs include norovirus, rotavirus, Campylobacter jejuni, and E. coli.
• E – Einstein / Boost brain development and cognition. After dining on HMOs, infantis releases a nutrient called sialic acid. (Remember this from the basic blueprint of the composition of HMOs?) Once absorbed from the gut into the blood stream, sialic acid participates in the growth of the baby’s brain, which is growing incredibly fast in the first year of life.
• N – NEC / Provide protection against necrotizing enterocolitis (NEC). NEC is a serious gastrointestinal disease affecting premature infants. The intestine becomes inflamed and infected and surgery may be needed to remove necrotic segments. Breastfed infants are at a 6-10-fold lower risk to develop NEC than formula-fed infants.
• Seal / Seal things up. Remember infantis, the bacteria that loves HMOs? According to a must-read article by Ed Yong, “After B. infantis digests H.M.O.s, it releases short-chain fatty acids, which feed an infant’s gut cells. Through direct contact, B. infantis also encourages gut cells to make adhesive proteins that seal the gaps between them, keeping microbes out of the blood stream.” (1) HMOs are higher in concentration in colostrum than in mature milk. Scientists wonder if this is one reason why so many infants who exclusively drink breast milk from women positive for HIV don’t get infected.

What a system.

References

1. Ed Yong. Breastfeeding the Microbiome. The New Yorker. July 22, 2016.  Link to article
2. Bode L. Human milk oligosaccharides: Every baby needs a sugar mama. 2012;22(9):1147-1162.
3. Bode L. Human milk oligosaccharides at the interface of maternal-infant health. Breastfeed Med. 2018;13(S1):S7.
4. Lactation College Course. Human Milk Composition. Presented by Barbara L. Philipp, MD, FAAP, FABM. Educational credits offered: 1 L-CERP (Detailed Content Outline: Development and Nutrition), 1 CEU, 1 CME. Human Milk Composition Course