Exercise training modifies xenometabolites in gut and circulation of lean and obese adults

Regular, moderate exercise modifies the gut microbiome and contributes to human metabolic and immune health. The microbiome may exert influence on host physiology through the microbial production and modification of metabolites (xenometabolites); however, this has not been extensively explored. We hypothesized that 6 weeks of supervised, aerobic exercise 3×/week (60%–75% heart rate reserve [HRR], 30–60 min) in previously sedentary, lean (n = 14) and obese (n = 10) adults would modify both the fecal and serum xenometabolome. Serum and fecal samples were collected pre‐ and post‐6 week intervention and analyzed by liquid chromatography/tandem mass spectrometry (LC–MS/MS). Linear mixed models (LMMs) identified multiple fecal and serum xenometabolites responsive to exercise training. Further cluster and pathway analysis revealed that the most prominent xenometabolic shifts occurred within aromatic amino acid (ArAA) metabolic pathways. Fecal and serum ArAA derivatives correlated with body composition (lean mass), markers of insulin sensitivity (insulin, HOMA‐IR) and cardiorespiratory fitness (V̇O2max$$ \dot{\mathrm{V}}{\mathrm{O}}_{2\max } $$), both at baseline and in response to exercise training. Two serum aromatic microbial‐derived amino acid metabolites that were upregulated following the exercise intervention, indole‐3‐lactic acid (ILA: fold change: 1.2, FDR p