Unintentional and Intentional Engineered Probiotics Using Xanthan Gum

Xanthan gum is a branched polysaccharide with complex sugar linkage structure and unique rheological properties making it useful as a food additive in a wide variety of processed foods at typical concentrations of 0.05-0.5% (w/w). Here, we show that the ability to utilize xanthan gum is surprisingly common in the individual human gut microbiomes of healthy adults and appears to be contingent on the activity of a single uncultured bacterium that is a member of an uncultured Ruminococcaceae genus. Using a metatranscriptomic approach followed by recombinant enzyme studies, we show that this keystone xanthan gum degrader depolymerizes xanthan gum with a novel glycoside hydrolase family 5 (GH5) enzyme that produces oligosaccharides that it can utilize via a series of additional enzymes. In some cases, oligosaccharide products of this pathway also cross-feed Bacteroides intestinalis strains equipped with their own distinct enzymatic pathway. Both xanthan gum loci were found with variable prevalence in industrialized human microbiome metagenomes but were absent in hunter-gatherers. Thus, consumption of a generally regarded as safe food additive, has apparently reinforced the existence of a food web between members of two different phyla of gut bacteria. Our findings have implications for the adaptability of the human gut microbiome to the introduction of new food additives on comparatively short timescales as well as utilizing the results of these events to engineer new orthogonal niches in members of the human gut microbiota for a future generation of probiotics.