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

Authors: KASPEREK, MIKAELA - University Of Illinois; PICCOLO, BRIAN - Arkansas Children'S Nutrition Research Center (ACNC); MOODY, BECKY - Arkansas Children'S Nutrition Research Center (ACNC); LAN, RENNY - Arkansas Children'S Nutrition Research Center (ACNC); MAILING, LUCY - University Of Illinois; GAO, XIOTIAN - University Of Illinois; HERNANDEZ-SAAVEDRA, DIEGO - University Of Illinois; WOODS, JEFFREY - University Of Illinois; ADAMS, SEAN - University Of California, Davis; ALLEN, JACOB - University Of Illinois

Submitted to: Physiological Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/18/2023
Publication Date: 3/22/2023
Citation: Kasperek, M., Piccolo, B., Moody, B., Lan, R., Mailing, L., Gao, X., Hernandez-Saavedra, D., Woods, J., Adams, S., Allen, J. 2023. Exercise training modifies xenometabolites in gut and circulation of lean and obese adults. Physiological Reports. 11(6):e15638. https://doi.org/10.14814/phy2.15638.
DOI: https://doi.org/10.14814/phy2.15638

Interpretive Summary: Gut bacteria has been shown to promote health and disease in humans, but the exact way it achieves this is still not well understood. Bacteria can ferment carbohydrates and other non-digested food into small molecules, which we refer to as xeno-metabolites. These xeno-metabolites can be absorbed and influence the activity and function of tissues in the body, which is a potential way that changes in the gut bacteria could influence host health and/or disease. A recent study showed that a moderate exercise program could change the composition of the gut microbiome in lean and obese adults that previously had limited exercise. Using this study, we wanted to know whether xeno-metabolites were also changed during exercise. The ACNC has built a profiling tool called the Xeno-Scan to measure many of these xeno-metabolites. Using this exercise study in adults will help us evaluate how this method works and guide our knowledge for future studies in children. We found that exercise changed both fecal and serum bacterial xeno-metabolites and these changes associated with certain amino acids pathways. Xeno-metabolites derived from aromatic amino acids correlated with clinical measures of body composition, insulin sensitivity, and cardio health. Specifically, serum indole-3-lactic acid and 4-hydroxyphenyllactic acid were key xeno-metabolites that had strong association with clinical endpoints in response to exercise training. The work from this study suggest that healthy lifestyle adaptations, like exercise, can possibly change the metabolism of bacteria residing in our gut. Data from this study will help guide our investigations in how diet and exercise can influence xeno-metabolites and health in children.

Technical Abstract: Regular, moderate exercise can modify 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 3x/wk (60-75% heart rate reserve [HRR], 30-60 minutes) 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 wk intervention and analyzed by liquid chromatography/tandem mass spectrometry (LC-MS/MS). Linear mixed models identified multiple fecal and serum xenometabolites responsive to exercise training. Further cluster and pathway analysis revealed the most prominent xenometabolic shifts occurred within aromatic amino acid metabolic pathways. Fecal and serum aromatic amino acid metabolites correlated with body composition (lean mass), markers of insulin sensitivity (insulin, HOMA-IR) and cardiorespiratory fitness (V'O2max), both at baseline and in response to exercise training. Two serum aromatic microbial-derived amino acid metabolites that were upregulated by exercise intervention, indole-3-lactic acid (ILA) and 4-hydroxyphenyllactic acid (4-HPLA), 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 the results bolster 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.