Glycoprofiling of Bifidobacterial Consumption of Human Milk Oligosaccharides Demonstrates Strain Specific, Preferential Consumption of Small Chain Glycans Secreted in Early Human Lactation

Abstract

The molecular basis by which human breast milk supports the development of a protective intestinal microbiome in infants is unknown. After lactose and lipids, human milk oligosaccharides (HMOs) are quantitatively the third largest and most diverse component of breast milk. In this work, glycomic profiling of HMO consumption by bifidobacteria using Fourier transform ion cyclotron resonance mass spectrometry reveals that one species, Bifidobacterium longum biovar infantis ATCC 15697, an isolate from the infant gut, preferentially consumes small mass oligosaccharides, representing 63.9% of the total HMOs available. These HMOs were detected in human breast milk at the onset and constantly through the first month of lactation by use of high performance liquid chromatography-chip time-of-flight mass spectrometry. Further characterization revealed that strain ATCC 15697 possesses both fucosidase and sialidase activities not present in the other tested strains. This work provides evidence that these small mass HMOs are selectively metabolized by select bifidobacterial strains and represent a potential new class of bioactive molecules functioning as prebiotics to facilitate a protective gut colonization in breast-fed newborns.

The role of human milk oligosaccharides in preventing necrotising enterocolitis and human immunodeficiency virus transmission

“…1 Glycoprofiling results by LoCascio et al 22 provide molecular and mechanistic evidence that specific strains of bifidobacteria have an affinity for selected classes of HMO. 8,11 This suggests that the diversity of specific oligosaccharide structures found within human milk do not provide a direct source of nutrition to the infant, but rather act as specific substrates to assist the growth of selected beneficial bacteria, that in their own right support the development and protection of the neonate.…”

“…21 An extraordinary characteristic of the intestinal environment of breastfed infants is the selective nourishment and protective support provided by the intestinal microbiotia. 22 The term "prebiotic" was introduced and defined by Gibson and Roberfroid as "a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon". 23,24 Although…”

“…8,11 This suggests that the diversity of specific oligosaccharide structures found within human milk do not provide a direct source of nutrition to the infant, but rather act as specific substrates to assist the growth of selected beneficial bacteria, that in their own right support the development and protection of the neonate. 22 N-acetylglucosamine oligosaccharides have been implicated as important cell wall components for bifidobacteria. 17 In the case of B. longum by infantis, this strain has the ability to preferentially consume the most abundant HMOs.…”

“…17 In the case of B. longum by infantis, this strain has the ability to preferentially consume the most abundant HMOs. 11,22 Antiadhesive effect of human milk oligosaccharides There is increasing evidence that oligosaccharides in human milk have a direct inhibitory effect on certain virulence capabilities of pathogenic microorganisms. 11 The destructiveness of most pathogenic microorganisms, e.g.…”

Biome engineering‐2020

“…The latter strategy allows also bystander bacteria to exploit the liberated sugars (Rakoff‐Nahoum et al ., 2016) with possibilities of cross‐feeding of enteric pathogens (Ng et al ., 2013). Some bifidobacteria showed preferences for fucosylated or small mass HMO typically produced through the first month of lactation (LoCascio et al ., 2007). The pioneers in that emerging field even suggested that mothers use a ‘glycan code’ when synthesizing HMO during the breastfeeding period that ‘instruct’ the gut in their infants what particular bacteria should get a nutritional push during a given time interval.…”