Helpful infant gut bacterium, Bifidobacterium infantis, uses special breast milk sugars to grow that other bacteria can’t use to grow.

Breast Milk Sugars Don’t Feed the Infant

As parents we often try to limit sugar for our kids. However, with breast milk – the sugars are essential food for helpful bacteria that grow in an infant’s gut. Along with fats, water, antioxidants from mom’s diet, antibodies, and other compounds, breast milk has a diversity of complex carbohydrate sugars. Called human milk oligosaccharides (HMO), these chains of carbohydrates bonded together are difficult to break apart. Humans do not make the enzymes that can break these breast milk sugar bonds [1, 2]. Our helpful gut bacteria do [3-6].

It's All About the Sugars, Baby
Infants and most gut bacteria don’t have the enzymes in their guts to digest the sugars that dominate human breast milk. The beneficial bacterium, Bifidobacterium infantis, uses enzyme Endo BI-1 for breaking sugars to use for food. This may explain why B. infantis dominates the gut of breast fed babies.

HMO sugars are extremely different from their refined and over-processed cousins that we use to sweeten our drinks and solid foods. Refined and processed sugars are primarily simple carbohydrates made of a few carbon molecules bound together (cartoon). These carbon bonds require little energy to break and digest, which is why they are considered a source of “fast energy”.

Feeding Our Invisible Friends

Why would human milk contain sugars that human infants can’t digest? It was a mystery for years. The answer came in 2008, the same year my first daughter was born, when the genome of Bifidobacterium longum subsp. infantis was sequenced. Now renamed B. infantis, this bacterial species had genes for breaking apart the complex carbohydrates that bound together HMOs [4, 6]. HMO’s nourish the microbial part of infant humans! Called the Milk-Oriented Microbiota (Mom) [7, 8], these bacteria dominate the gut microbiome of breast milk-fed infants. Formula-fed babies often lack these bacteria or the MOMs are in low abundance.

HMO sugars are also very different from the carbohydrates found in the milk of other mammals. Pick your favorite mammal – dog, cat, mouse, gorilla, horse, cow, lemur, goat, elephants, humans, whatever, female mammals produce milk to nourish their infants. However, human milk as more of these complex sugars than other mammals. One hypothesis is that this is due to how much the brain needs to develop in that first year of life. HMOs are also diverse in structure and type. Some are only a few sugars linked together, while others have the sugars attached to proteins (“glycoproteins”) or fats (“glycolipids”) [9, 10]

What Does B. infantis Need to Grow?

Which of the many types of HMOs can B. infantis use for growth? B. infantis was known to grow on the HMOs that were free carbohydrates. But what about glycoproteins or glycolipids? What do these bacteria need? The sugars or the proteins and lipids the sugars are attached to? The Mills lab at the University of California at Davis leads the field of breastmilk-microbiome research. They found that the bacterium needs the sugars of the HMOs to grow, they cannot grow on the proteins found in breast milk [3]. To grow on the sugar portion of the glycoproteins, the sugars and proteins must be cut apart.

How do these MOMs, these beneficial B. infantis bacteria, actually digest breast milk? What is the sword they use to cut apart the carbohydrates? The Mills’ lab found that a single enzyme at the bacterium’s cell wall – “endo B-N acetylglucosaminidase” (EndoBI-1) – removed the links between sugar and protein. EndoBI-1 freed the sugar for B. infantis to degrade further and grow [3]. Additionally, they tested the growth of Bifidobacteria which are not found in infant guts, such as B. animalis subsp. lactis. Only B. infantis could grow on the sugars released by EndoBI-1. Suggesting that the sugars released by EndoBI-1 from the HMO glycoproteins are what allow B. infantis to dominate the infant gut microbiome [3].

Breast milk contains a higher diversity of sugars than formula. These different types of sugars feed different bacteria.
Breast milk contains a higher diversity of sugars than formula. These different types of sugars feed different bacteria.

Breast Milk Research Feeds Formula Improvements

So what does this mean for formula-fed babies? Can this breast milk research help develop better formulas? Yes, these glycoproteins are found in cow milk too, but at low abundance. Scientists and nutritionists are working to figure out ways to concentrate the glycoproteins from cow whey protein concentrate. If so, these cow milk sugars could be used in formula to serve as novel prebiotic substrates to selectively grow B. infantis at levels similar to that of breast milk fed babies.

Basic research studies such as these are phenomenal. Not only do they help us unravel how our microbiomes and the human body interact, but the findings can be translated to help those babies that cannot be breast-fed for whatever reason. Although the lead author, Dr. David Mills, is always quick to say that “Breast milk is the only food perfectly evolved for human babies”.

For additional information on the infant microbiome see this post and further detail in my Science and Sensibility guest post.

REFERENCES

 

  1. Smilowitz JT, Lebrilla CB, Mills DA, German JB, Freeman SL: Breast Milk Oligosaccharides: Structure-Function Relationships in the Neonate. Annu Rev Nutr 2014, 34(1):143-169.
  2. Kunz C, Rudloff S, Baier W, Klein N, Strobel S: Oligosaccharides in Human Milk: Structural, Functional, and Metabolic Aspects. Annu Rev Nutr 2000, 20(1):699-722.
  3. Karav S, Le Parc A, Maria Leite Nobrega de Moura Bell J, Frese SA, Kirmiz N, Block DE, Barile D, Mills DA: Oligosaccharides released from milk glycoproteins are selective growth substrates for infant-associated bifidobacteria. Appl Environ Microbiol 2016.
  4. Sela DA, Chapman J, Adeuya A, Kim JH, Chen F, Whitehead TR, Lapidus A, Rokhsar DS, Lebrilla CB, German JB et al: The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome. Proceedings of the National Academy of Sciences 2008, 105(48):18964-18969.
  5. Wang M, Li M, Wu S, Lebrilla CB, Chapkin RS, Ivanov I, Donovan SM: Fecal microbiota composition of breast-fed infants is correlated with human milk oligosaccharides consumed. J Pediatr Gastroenterol Nutr 2015, 60(6):825-833.
  6. Zivkovic AM, German JB, Lebrilla CB, Mills DA: Human milk glycobiome and its impact on the infant gastrointestinal microbiota. Proceedings of the National Academy of Sciences 2011, 108(Supplement 1):4653-4658.
  7. Zivkovic AM, Lewis ZT, German JB, Mills DA: Establishment of a Milk-Oriented Microbiota (MOM) in Early Life: How Babies Meet Their Moms. Functional Food Reviews 2013, 5(1):3-12.
  8. Frese Steven A, Mills David A: Birth of the Infant Gut Microbiome: Moms Deliver Twice! Cell Host & Microbe 2015, 17(5):543-544.
  9. Bode L: Human milk oligosaccharides: prebiotics and beyond. Nutr Rev 2009, 67.
  10. Bode L, Jantscher-Krenn E: Structure-Function Relationships of Human Milk Oligosaccharides. Advances in Nutrition: An International Review Journal 2012, 3(3):383S-391S.

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