738-P: Meta’omic Analysis of Elite Athletes Identifies a Performance-Enhancing Microbe that Functions via Lactate Metabolism

Abstract

The human gut microbiome encodes a vast metabolic repertoire with direct impacts on many aspects of host physiology, yet it is unknown whether it has any bearing on physical performance or exercise. To begin to address this question, we performed a longitudinal metagenomic analysis on runners in the 2015 Boston Marathon to identify microbiome features associated with intense physical activity. The strongest microbiome feature enriched post-marathon was an increase in the abundance of the bacterial genus Veillonella. We isolated Veillonella atypica directly from the marathon runners, and found that upon inoculation in laboratory mice in an AB/BA crossover study testing treadmill runtime to exhaustion, runtime was increased 13% in a V. atypica-dependent manner. V. atypica has a preference for lactate as its primary carbon source, and we find using shotgun metagenomic analysis in a cohort of elite athletes that every differentially expressed gene family in the pathway metabolizing lactate to the short-chain fatty acid propionate is at higher relative abundance post-exercise. Using 13C3-labeled lactate in mice we demonstrate that serum lactate crosses the epithelial barrier into the lumen of the gut. We also show that intrarectal instillation of propionate is sufficient to reproduce the increased treadmill runtime performance observed with V. atypica gavage. Taken together, these studies reveal that V. atypica improves runtime via its metabolic conversion of exercise-induced lactate into propionate, thereby identifying a natural, microbiome-encoded enzymatic process that enhances athletic performance. Disclosure A. Kostic: Stock/Shareholder; Self; DeepBiome Therapeutics, Inc., FitBiomics, Inc. Funding American Diabetes Association/Pathway to Stop Diabetes (1-17-INI-13)