Milk’s role in directing the infant microbiome

by David Sela

Background

Since mammals have evolved in a world dominated by microbes,
it is essential to not only consider milk’s direct role in infant health, but to understand milk’s influence on the infant’s resident microbial
inhabitants. This so-called microbiota is responsible for complementing enzymatic deficiencies in their mammalian hosts by harvesting energy from otherwise
indigestible foods. This is in addition to modulating the immune system and
restricting pathogen access to preferred colonization sites among other benefits. Accordingly, the
dramatic evolutionary link between milk and one such infant-associated
bacterium, Bifidobacterium longum subsp. infantis (B. infantis) has
been reported: Sela, D.A. et al., PNAS (2008) PMID:19033196

 

 

B. infantis is often enriched in breast-fed infants through their atypical ability to utilize human milk oligosaccharides (HMOs). HMOs are
soluble glycans indigestible by infant host enzymes, thus do not
possess a known nutritive function. The genome sequence of this infant gut symbiont
possesses discernable features which evolutionarily link infant, milk and their associated beneficial microbes. These milk-active genes, and their encoded metabolic networks, further reinforce the use of dairy based applications to enrich the bifidobacterial content in infants and other populations. Thus the completion of the B. infantis genome project has elevated this bacterium to the preferred model in which to study milk’s dual benefit to consumers and their healthy gut microbes. 

This IMGC portal project disseminates information regarding B. infantis genes active on milk substrates encountered within the infant gut.

 

Genomics and glyomics of B. infantis utilization of human milk oligosaccharides

 

Any discussion of linking the milk glycome with the B. infantis genome requires understanding the HMO structures themselves. A detailed examination of the HMO core structure is provided here.

Next, the list of genes believed to be involved in HMO utilization by B. infantis can be accessed here.

A general protocol for surveying additional bacterial genomes as more are publically deposited can be accessed here.

The distribution of milk-related genes in other members of the human gut consortium can be found here.

Finally, a pathway tools  database constructed from the B. infantis genome sequence can be downloaded here.

 

 Additional References

Particularly useful references regarding milk oligosaccharides and their function enriching bifidobacteria:

 

Coppa,
G. V., S. Bruni, et al. (2004). “The first prebiotics in humans: human
milk oligosaccharides.” J Clin Gastroenterol 38(6 Suppl): S80-3.

Engfer, M. B., B. Stahl, et al.
(2000). “Human milk oligosaccharides are resistant to enzymatic hydrolysis
in the upper gastrointestinal tract.” Am J Clin Nutr 71(6): 1589-96.

German, J. B., S. L. Freeman, et
al. (2008). “Human milk oligosaccharides: evolution, structures and
bioselectivity as substrates for intestinal bacteria.” Nestle Nutr
Workshop Ser Pediatr Program
62:
205-18; discussion 218-22.

Katayama, T., A. Sakuma, et al.
(2004). “Molecular cloning and characterization of Bifidobacterium bifidum
1,2-alpha-L-fucosidase (AfcA), a novel inverting glycosidase (glycoside
hydrolase family 95).” J Bacteriol 186(15): 4885-93.

Kitaoka, M., J. Tian, et al.
(2005). “Novel putative galactose operon involving lacto-N-biose
phosphorylase in Bifidobacterium longum.” Appl Environ Microbiol 71(6): 3158-62.

Kunz, C. and S. Rudloff (1993).
“Biological functions of oligosaccharides in human milk.” Acta
Paediatr
82(11): 903-12.

LoCascio, R. G., M. R.
Ninonuevo, et al. (2007). “Glycoprofiling of bifidobacterial consumption
of human milk oligosaccharides demonstrates strain specific, preferential
consumption of small chain glycans secreted in early human lactation.” J
Agric Food Chem
55(22): 8914-9.

Newburg, D. S. (2000).
“Oligosaccharides in human milk and bacterial colonization.” J
Pediatr Gastroenterol Nutr
30 Suppl
2
: S8-17.

Ninonuevo, M. R., Y. Park, et
al. (2006). “A strategy for annotating the human milk glycome.” J
Agric Food Chem
54(20): 7471-80.

Sela, D. A., J. Chapman, et al.
(2008). “The genome sequence of Bifidobacterium longum subsp. infantis
reveals adaptations for milk utilization within the infant microbiome.” Proc
Natl Acad Sci U S A
105(48):
18964-9.

Ward, R. E., M. Ninonuevo, et
al. (2006). “In vitro fermentation of breast milk oligosaccharides by
Bifidobacterium infantis and Lactobacillus gasseri.” Appl Environ
Microbiol
72(6): 4497-9.