Coevolution With Milk Has Influenced Innovation In The Bifidobacterium Longum Subsp. Infantis Genome To Utilize Sialylated And Fucosylated Milk Oligosaccharides

Following birth, the breast-fed infant gastrointestinal tract is rapidly colonized by a microbial consortium often dominated by bifidobacteria. This numerical advantage competitively excludes pathogen colonization in addition to conferring other health benefits to the developing neonate. To resolve the genesis of this milk-mediated enrichment, we have previously demonstrated that select bifidobacterial phylotypes utilize specific human milk oligosaccharides (HMOs) secreted early in lactation1. Accordingly, HMO ubiquity in the infant gut has profoundly influenced the remodeling of the Bifidobacterium longum subsp. infantis genome towards milk glycan utilization at the expense of plant-derived sugars. This includes the innovation of several catabolic processes previously unknown in the bifidobacteria2. Biochemical characterizations of these catabolic enzymes have confirmed that they are indeed active on sialylated and fucosylated oligosaccharides and their derivatives. Moreover, bifidobacterial glycosidases exhibit unique expression profiles dependant on growth on lactose or HMO as a sole carbohydrate source. Temporal tracking of both neutral and acidic oligosaccharide consumption has revealed the specific compositions preferred by B. longum subsp. infantis while subsisting on these milk sugars. Furthermore, an array of evolutionarily divergent oligosaccharide transporters are employed in extracellular recognition and transmembrane import of specific milk glycan structures. Finally, next generation sequencing and chromosomal microarray analysis of additional bifidobacterial genomes has generalized these findings to a clade typically isolated from breast-fed infants. These studies have functionally verified, in part, the genomic mechanism by which B. longum subsp. infantis interacts with milk-borne molecules, and strongly supports a milk-dependant colonization strategy. Thus milk should no longer be regarded solely as consequential to the evolution of the mammalian genome, but as a selective imperative that has directed the fundamental structure of the mammalian microbiome as well.

1. LoCascio, R.G. et al. 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, 8914-8919 (2007).

2. Sela, D.A. et al. 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, 18964-18969 (2008).