The human gut microbiome is a dynamic ecosystem with prolific health connotations. Physical activity is emerging as a potent regulator of human microbiome composition. PURPOSE: This study examined changes in the gut microbiome of a world-class ultramarathon runner before and after competing in the Western States Endurance Run (WSER), a 163 km mountain footrace. METHODS: Anthropometrics and body composition were assessed and the ultramarathoner’s submaximal and maximal performance profiles were evaluated. Gut microbiome analyses were performed at four time-points: 21 wk and 2 wk before and 2 h and 10 d after WSER. RESULTS: Aerobic power (VO₂max) was 4.24 L/min (66.7 ml/kg/min), and running economy (51.1 ml/kg/min at 268 m/min) and lactate threshold (~83% VO₂max) values were comparable to that of highly trained distance runners. Two hours post-race, considerable changes in the ultrarunners gut microbiome were observed. Alpha diversity (Shannon Diversity Index) increased from 2.73 to 2.80 and phylum-level bacterial composition (Firmicutes/Bacteroidetes ratio) rose from 4.4 to 14.2. Underlying these macro-level microbial alterations were demonstrable increases in select bacterial genera such as Veillonella (+14,229%) and Streptococcus (+438%) concomitant with reductions in Alloprevotella (-79%) and Subdolingranulum (-50%). CONCLUSIONS: To our knowledge, this case study shows the most rapid and pronounced shifts in human gut microbiome composition after acute exercise in the human literature. These findings provide yet another example of how exercise can be a powerful modulator of human health.