Breast milk provides an inexpensive, nutrient-filled source of food for babies. Because of this, the American Academy of Pediatrics and the WHO recommend new mothers to exclusively breast feed their babies for the first six months of life, and continue up to two years (supplemented with other foods). Breast milk provides maternal antibodies, which protect the immature immune system. It has a balance of carbohydrate, protein, and fats that are hard to reproduce in formula. It provides digestive enzymes and hormones necessary in early life. And new research published in Applied and Environmental Microbiology suggests specific components of breast milk help to shape the baby’s nascent gut microbiome as well.
First author Sercan Karav, working with senior author David Mills, hypothesized that some of the milk constituents might specifically interact with human gut microbes. Bifidobacterium longum subspecies infantis is one of the first colonizers of infants after birth, where its ability to produce lactic acid and lower the pH is thought to prevent growth of unwanted microbial species. Scientists already know that milk sugars support B. infantis growth, but exactly which component is the bacterium’s favorite food has been a mystery, since human milk sugars can be found in both as polysaccharide chains and attached to other milk components as glycolipids and glycoproteins. If the preferred component is discovered, reasoned the scientists, it could be incorporated as a prebiotic – something that encourages the growth of healthy microbiome members.
B. infantis has a number of enzymes that can break down various sugar substrates found in human milk, and one such recently discovered enzyme is an endo-beta-N-acetyleglucosamnidase (EndoBI-1). Karav posited that this enzyme may release N-linked glycoprotein components which could then be used as food. To test this idea, the enzyme was recombinantly expressed in E. coli and used to release N-glycans from whey glycoproteins. When fed the released N-glycans as their only carbon source, B. infantis grew well, while another Bifidobacterium species, B. lactis, was not. B. lactis does not grow well on human milk, nor does it have the EndoBI-1 enzyme, demonstrating the specificity of B. lactis as a human milk-consuming species.
To specifically show that these N-glycans are B. infantis’ preferred food source, the scientific team compared bacterial growth on three different food sources: untreated whey protein, purified N-glycans from whey protein, and whey protein that had had its N-glycans removed. This last condition was a key control: if the bacteria are using N-glycans with other components, they should grow fine even with N-glycans removed. Instead, the bacteria didn’t grow at all when N-glycans were removed, showing the vital role played by this component in B. infantis growth (see figure, right).
The source of whey – milk proteins – used in the study was also of note. Not all new mothers are able to breast feed their babies, for a variety of reasons, and must rely on formula in the first few months. Preparing a formula using nonhuman milk sources that confers similar health benefits as human breast milk has proven difficult, and study after study has supported the use of breast milk over formula. The results show that N-glycans derived from cow’s milk (used in this study) can promote growth of the important infant human microbiome member. Incorporation of these N-glycans may better mimic the benefits of human breast milk, with potential to benefit breast-fed and bottle-fed babies.
-- Julie Wolf