Life-long exercise training and inherited aerobic endurance capacity produce converging gut microbiome signatures in rodents.

High aerobic endurance capacity can be acquired by training and/or inherited. Aerobic exercise training (AET) and aging are linked to altered gut microbiome composition, but it is unknown if the environmental stress of exercise and host genetics that predispose for higher exercise capacity have similar effects on the gut microbiome during aging. We hypothesized that exercise training and host genetics would have conserved effects on the gut microbiome across different rodents. We studied young sedentary (Y-SED, 2-month-old) mice, old sedentary (O-SED, 26-month-old) mice, old mice with life-long AET (O-AET, 26-month-old), and aged rats selectively bred for high (HCR [High Capacity Runner], 21-month-old) and low (LCR [Low Capacity Runner], 21-month-old) aerobic capacity. Our results showed that O-SED mice had lower running capacity than Y-SED mice. The fecal microbiota of O-SED mice had a higher relative abundance of Lachnospiraceae, Ruminococcaceae, Turicibacteriaceae, and Allobaculum, but lower Bacteroidales, Alistipes, Akkermansia, and Anaeroplasma. O-AET mice had a higher running capacity than O-SED mice. O-AET mice had lower fecal levels of Lachnospiraceae, Turicibacteriaceae, and Allobaculum and higher Anaeroplasma than O-SED mice. Similar to O-AET mice, but despite no exercise training regime, aged HCR rats had lower Lachnospiraceae and Ruminococcaceae and expansion of certain Bacteroidales in the fecal microbiome compared to LCR rats. Our data show that environmental and genetic modifiers of high aerobic endurance capacity produce convergent gut microbiome signatures across different rodent species during aging. Therefore, we conclude that host genetics and life-long exercise influence the composition of the gut microbiome and can mitigate gut dysbiosis and functional decline during aging.