Two untargeted metabolomics reveals yogurt-associated metabolic alterations in women with multiple metabolic disorders from a randomized controlled study.

The beneficial role of yogurt on metabolic profile has been widely reported. Yet, few studies have intended to describe the integrated metabolic alterations in response to yogurt. Yogurt and milk (220 g/d) were given to 48 and 44 obese women with metabolic syndrome and nonalcoholic fatty liver disease for 24 weeks in a randomized controlled trial (registered at http://www.chictr.org.cn as ChiCTR-IPR-15006801). Fasting serum samples were collected before and after intervention for global, untargeted metabolomics based on H nuclear magnetic resonance (NMR) and ultra-high-performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry (UPLC-Q-TOF-MS) (in positive and negative ion modes). Multivariable statistical analysis and pathway analysis were conducted. In both H NMR and UPLC-Q-TOF-MS metabolomics, no clustering was observed between the two groups at baseline. While, a clear clustering was shown after intervention, and the yogurt group had significantly different metabolic status from the milk. The metabolites that contributed mostly to class separation were identified, and involved into pathway analysis. Pathways on amino acids metabolism, fatty acid oxidation, cholesterol catabolism and choline metabolism significantly changed after yogurt intervention. The study revealed the integrated metabolic alterations in response to yogurt via two metabolomics approaches, suggesting the potential mechanisms of yogurt against metabolic disorders. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-15006801. Registered 20 July 2015, http://www.chictr.org.cn/ ChiCTR-IPR-15006801. SIGNIFICANCE: Both review from prospective studies and our randomized clinical trial showed the protective role of yogurt against multiple metabolic disorders. However, they were focus on targeted glucose, lipid, and other metabolic indicators, which were only part of human metabolism, failing to show an integrated metabolic feature on yogurt. Therefore, two global, untargeted metabolomics were applied in our current randomized clinical trial, trying to uncover the significant metabolic alterations characterizing the effects of yogurt on obese women with multiple metabolic disorders, and to explore the potential biological mechanisms of yogurt. The finding will shed light on a more comprehensive picture of how yogurt affects host metabolism, and provide theoretical foundation for dietary prevention of chronic diseases.