Abstract
Galactooligosaccharides (GOS) are prebiotic carbohydrates that impart changes in the gut bacterial composition of formula-fed infants to more closely resemble that of breast-fed infants. Consuming human milk oligosaccharides (HMOs) provides specific bacterial strains with an advantage for colonizing the infant intestine. These same effects are seen in infants after GOS consumption, however GOS are very complex mixtures and the underlying molecular mechanisms of how GOS mimic HMOs are relatively unknown. Here we studied the effects of GOS utilization on a prominent gut symbiont, Bacteroides thetaiotaomicron, which has been previously shown to consume HMOs via mucin O-glycan degradation pathways. We show that several pathways for targeting O-mucin glycans are activated in B. thetaiotaomicron by GOS, as well as the galactan utilization sytem. Characterization of the endo-galactanase from this system identified activity on various longer GOS substrates while a subset of GOS compounds were identified as potential activators of mucin glycan metabolism in B. thetaiotaomicron. Our results show that GOS functions as an inducer of mucin-glycan pathways while providing a nutrient source in the form of β-(1 → 4)-galactan. These metabolic features of GOS mixtures may serve to explain the beneficial effects that are seen for GOS supplemented infant formula.
Highlights
Individual monosaccharide components[13,14]
We identified two distinct mechanisms directed at GOS metabolism by B. thetaiotaomicron: firstly, extended linear β-(1 → 4)-linked GOS molecules were degraded via the action of an extracellular GH53 endo-β-(1 → 4)-galactanase that is encoded within a galactan utilization PUL
We show that specific GOS molecules mimic Human milk oligosaccharides (HMOs) by expressing enzymes and transport components from PULs indicated in mucin-O-glycan degradation in B. thetaiotaomicron while a specific endo-β-galactanase directed at dietary fibre catabolism plays an important role in GOS degradation
Summary
Individual monosaccharide components[13,14]. These catabolic systems are arranged in defined operons called polysaccharide utilization loci (PULs) that make up approximately 20% of the B. thetaiotaomicron genome and target specific polysaccharides for degradation[4,5]. We show that specific GOS molecules mimic HMOs by expressing enzymes and transport components from PULs indicated in mucin-O-glycan degradation in B. thetaiotaomicron while a specific endo-β-galactanase directed at dietary fibre catabolism plays an important role in GOS degradation. This is the first study to identify the molecular details of GOS utilization by B. thetaiotaomicron from which we can speculate how specific GOS compounds may elicit responses similar to HMOs. This is the first study to identify the molecular details of GOS utilization by B. thetaiotaomicron from which we can speculate how specific GOS compounds may elicit responses similar to HMOs These results provide a basis for making more selective prebiotic preparations for infant formulas and for broader prebiotic and dietary fibre applications
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