Think Globally, Act Locally: Regulated Deployment of Polysaccharide Degradation Abilities by our Symbiotic Gut Bacteria

Symbiotic microorganisms expand human digestive physiology by providing an armament of glycan‐degrading enzymes that are absent in the human genome. Dietary glycans, mixed with endogenous mucus, present a diverse menu of carbohydrates, which the trillions of microorganisms that inhabit the colon have adapted strategies to sense, triage and degrade. Understanding which of the hundreds of species of gut microbes consume each nutrient, how glycan degradation abilities vary among taxa and what molecular mechanisms are involved, are central problems in defining the relationship between diet, microbiota and health. We are taking microbiological, genomic, genetic and biochemical approaches to address these problems. Our results have revealed that members of the Bacteroidetes are major contributors to complex carbohydrate digestion and rely on expression of discrete gene clusters that each encodes the requisite proteins to catabolize a particular glycan. Each gene cluster is activated by a locally encoded transcription factor that participates in carbohydrate sensing and metabolism. In a single bacterium, many dozen individual gene clusters could simultaneously be triggered to respond to available nutrients. Yet, in experimental conditions, there is an ordered progression of carbohydrate utilization, reminiscent of catabolite repression. We are exploring the phenomenon of catabolite prioritization in gut Bacteroidetes and the mechanisms involved. Our results reveal that sensing and metabolic triaging of glycans varies among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment.