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

• Published in: Physiological reports Vol. 11; no. 6; pp. e15638 - n/a
• Main Authors: Kasperek, Mikaela C., Mailing, Lucy, Piccolo, Brian D., Moody, Becky, Lan, Renny, Gao, Xiaotian, Hernandez‐Saavedra, Diego, Woods, Jeffrey A., Adams, Sean H., Allen, Jacob M.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.03.2023; John Wiley and Sons Inc; Wiley
• Subjects: Adult; Aerobics; Amino acids; Bile; Body composition; Body mass index; Cardiorespiratory fitness; Chromatography, Liquid; Disease; Exercise; Exercise - physiology; Feces; Fitness training programs; Gastrointestinal surgery; Heart rate; Humans; Insulin; Insulin Resistance; Intervention; Intestinal microflora; Lactic acid; Liquid chromatography; Longitudinal studies; Mass spectroscopy; Metabolic pathways; Metabolism; Metabolites; microbiome; Microbiomes; Microbiota; Obesity; Obesity - metabolism; Original; Physical fitness; Physical training; Physiology; Population studies; Questionnaires; Tandem Mass Spectrometry; Weight control; Womens health; xenometabolism; exercise; metabolites; microbiome; xenometabolism; obesity
• ISSN: 2051-817X
• DOI: 10.14814/phy2.15638

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 < 0.05) and 4‐hydroxyphenyllactic acid (4‐HPLA: fold change: 1.3, FDR p < 0.05), share metabolic pathways within the microbiota and were associated with body composition and markers of insulin sensitivity at baseline and in response to training. These data provide evidence of physiologically relevant shifts in microbial metabolism that occur in response to exercise training, and reinforce the view that host metabolic health influences gut microbiota population and function. Future studies should consider the microbiome and xenometabolome when investigating the health benefits of exercise. Xenometabolomic responses to exercise were different between lean and obese adults, despite some shared adaptations. Microbial metabolites associated with body composition, markers of insulin sensitivity, and cardiorespiratory fitness, both at baseline and in response to exercise training. These data suggest microbial metabolites should be carefully considered as contributors to exercise adaptations and human health.