Gut microbiota responses to aerobic exercise training are intensity-dependent and associated with individual improvements in V.O2max

Background Exercise intensity is a key determinant of physiological adaptations to training, yet its influence on the gut microbiota remains poorly understood. Furthermore, considerable interindividual variability in aerobic training adaptations exists, but factors associated with this variability are still unclear. We investigated how six weeks of cycling in the moderate, heavy, and severe exercise intensity domains influenced V . ⁢ O 2 ⁢ max and the gut microbiota in healthy adults. Methods Sixty-five healthy young adults were randomized to one of five cycling intervention groups according to exercise intensity domains (MOD: n = 11; HVY1: n = 10; HVY2: n = 13; HIIT: n = 11; SIT: n = 12), or a non-intervention control group (CON: n = 8). For analysis, groups were combined at the domain level into moderate (MOD: n = 11), heavy (HVY; HVY1 + HVY2: n = 23), and severe (SVR; HIIT + SIT: n = 23). All groups except SIT were work matched. Participants performed 3 training sessions weekly for 6 weeks. Stool samples, serum, and a 3-day dietary food log were collected before (PRE) and after (POST) the 6-week intervention. Results HVY and SVR exercise significantly increased V . ⁢ O 2 ⁢ max and gut microbiota alpha diversity, whereas changes in the MOD group were not statistically significant. Participants with larger improvements in V . ⁢ O 2 ⁢ max (responders) exhibited distinct gut microbiota profiles differing from those with limited improvements (non-responders), and proxy markers of gut permeability and inflammation further distinguished non-responders. Holdemanella was consistently associated with non-response and was the primary discriminating feature in a decision-tree classification model. Conclusion Six weeks of HVY and SVR intensity cycling was associated with improvements in V . ⁢ O 2 ⁢ max and detectable changes in the gut microbiota under the conditions of this intervention; the dose–response relationship and any physiological threshold remain to be determined. Distinct gut microbiota profiles were associated with the magnitude of improvement in V . ⁢ O 2 ⁢ max across intensity domains, raising the possibility that the gut microbiota contributes to interindividual differences in aerobic training response.