Physiology of Consumption of Human Milk Oligosaccharides by Infant Gut-associated Bifidobacteria

Abstract

The bifidogenic effect of human milk oligosaccharides (HMOs) has long been known, yet the precise mechanism underlying it remains unresolved. Recent studies show that some species/subspecies of Bifidobacterium are equipped with genetic and enzymatic sets dedicated to the utilization of HMOs, and consequently they can grow on HMOs; however, the ability to metabolize HMOs has not been directly linked to the actual metabolic behavior of the bacteria. In this report, we clarify the fate of each HMO during cultivation of infant gut-associated bifidobacteria. Bifidobacterium bifidum JCM1254, Bifidobacterium longum subsp. infantis JCM1222, Bifidobacterium longum subsp. longum JCM1217, and Bifidobacterium breve JCM1192 were selected for this purpose and were grown on HMO media containing a main neutral oligosaccharide fraction. The mono-and oligosaccharides in the spent media were labeled with 2-anthranilic acid, and their concentrations were determined at various incubation times using normal phase high performance liquid chromatography. The results reflect the metabolic abilities of the respective bifidobacteria. B. bifidum used secretory glycosidases to degrade HMOs, whereas B. longum subsp. infantis assimilated all HMOs by incorporating them in their intact forms. B. longum subsp. longum and B. breve consumed lacto-N-tetraose only. Interestingly, B. bifidum left degraded HMO metabolites outside of the cell even when the cells initiate vegetative growth, which indicates that the different species/subspecies can share the produced sugars. The predominance of type 1 chains in HMOs and the preferential use of type 1 HMO by infant gut-associated bifidobacteria suggest the coevolution of the bacteria with humans.

Diverse galactooligosaccharides consumption by bifidobacteria: implications of β-galactosidase—LacS operon

“…32) In contrast, strains belonging to B. breve, B. bifidum, and B. longum, which are frequently found in infant's intestines, 19) all showed gradual growth with GOS-P and utilized the DP2 fraction of GOS-M, consisting mainly of lactose. Asakuma et al demonstrated that B. breve does not decrease HMO concentrations until lactose has been expended, 33) indicating that these infant-borne bifidobacteria are highly adapted to this substrate. At the same time, it is noteworthy that B. breve and B. longum utilized the small DP4 fraction of GOS-P in addition to the major DP3 fraction.…”

The role of early life nutrition in the establishment of gastrointestinal microbial composition and function

“…72,73 Of particular interest to researchers is the ability of Bifidobacterium to metabolize HMOs. Certain HMO show bifidogenic effects in vitro, 72,74 selectively stimulating the growth of certain commensal bacteria often identified in BF infants, such as B. infantis, B. bifidum, B. breve and B. longum. 34,42 Additionally, HMOs also serve as a carbon source for various species of Bacteroides common to the infant GI tract, but do not function as a substrate for other members of the Firmicutes phylum or Bifidobacterium species primarily present in adults, such as B. adolescentis and B. animalis; these microbes lack the enzymatic capacity to break down and consume HMOs.…”

Genomics of the Genus Bifidobacterium Reveals Species-Specific Adaptation to the Glycan-Rich Gut Environment

“…infantis, a typical fecal isolate from (breast-fed) infants, encompasses a gene cluster predicted to encode GHs and carbohydrate transporters necessary for the import and metabolism of HMOs (5). This 43-kb gene cluster encodes a variety of predicted or proven catabolic enzymes, such as fucosidases, sialidases, a ␤-hexosaminidase, and ␤-galactosidases, as well as extracellular solute binding proteins and permeases that are devoted to HMO metabolism (5,(54)(55)(56). Moreover, the genome of this microorganism contains a complete urease operon predicted to be involved in the utilization of urea, representing an important nitrogen source in milk (5).…”