Manipulating the Gut Microbiome to Improve Health

Abstract

The human gut microbiome is rapidly gaining attention for its connections to a long list of health and disease states, presenting new opportunities to modulate human health using microbiome therapeutics. In this dissertation, I will explore the concept of the microbiome as a metabolic “organ,” where the metabolic reactions encoded in microbial genomes can have profound effects on the health of the host. In the context of athletic performance, distinct exercise-associated microbiome states are characterized by increases in distinct microbial taxa, some of which are relatively unique in their preference for lactate as a carbon source. We show that isolates of lactate-utilizing members of the genus Veillonella can improve athletic performance in mice, and further show that the principal metabolic byproduct of Veillonella, propionate, mimics this performance enhancing effect. In a similar vein, we investigate the metabolic potential for probiotic E. coli Nissle to absorb glucose in the context of diabetic postprandial hyperglycemia. We show that E. coli Nissle can reduce the glycemic impact of a large glucose bolus, however this effect is not dependent on E. coli glucose metabolism. Thus, while we observe improvements in glycemic profiles, these improvements are not due to a metabolic interaction, but likely a physiological one. Overall, the work I describe here represents a step towards manipulating the gut microbiome to improve health and manage disease. By focusing on the molecular effectors at the host-microbiome interface, we can target and modify those signals to the benefit of host wellbeing.