Multidisciplinary approach combining food metabolomics and epidemiology identifies meglutol as an important bioactive metabolite in tempe, an Indonesian fermented food

Marvin N Iman; Danielle E Haslam; Liming Liang; Kai Guo; Kaumudi Joshipura; Cynthia M Pérez; Clary Clish; Katherine L Tucker; JoAnn E Manson; Shilpa N Bhupathiraju; Eiichiro Fukusaki; Jessica Lasky-Su; Sastia P Putri

doi:10.1016/j.foodchem.2024.138744

Multidisciplinary approach combining food metabolomics and epidemiology identifies meglutol as an important bioactive metabolite in tempe, an Indonesian fermented food

Food Chem. 2024 Jul 15:446:138744. doi: 10.1016/j.foodchem.2024.138744. Epub 2024 Feb 16.

Authors

Affiliations

¹ Department of Biotechnology, Graduate School of Engineering, Osaka University, Japan.
² Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
³ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁴ Center for Clinical Research and Health Promotion, Graduate School of Public Health, University of Puerto Rico Medical Sciences Campus, Puerto Rico, USA.
⁵ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Center for Clinical Research and Health Promotion, Graduate School of Public Health, University of Puerto Rico Medical Sciences Campus, Puerto Rico, USA.
⁶ Department of Biostatistics and Epidemiology, Graduate School of Public Health, University of Puerto Rico Medical Sciences Campus, Puerto Rico, USA.
⁷ Broad Institute of Massachusetts Institute of Technology and Harvard, USA.
⁸ Department of Biomedical and Nutritional Sciences, University of Massachusetts Lowell, USA.
⁹ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹⁰ Department of Biotechnology, Graduate School of Engineering, Osaka University, Japan; Industrial Biotechnology Initiative Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Japan; Osaka University-Shimadzu Omics Innovation Research Laboratories, Osaka University, Japan.
¹¹ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹² Department of Biotechnology, Graduate School of Engineering, Osaka University, Japan; Osaka University-Shimadzu Omics Innovation Research Laboratories, Osaka University, Japan. Electronic address: sastia_putri@bio.eng.osaka-u.ac.jp.

PMID: 38432131
DOI: 10.1016/j.foodchem.2024.138744

Abstract

This study introduces a multidisciplinary approach to investigate bioactive food metabolites often overlooked due to their low concentrations. We integrated an in-house food metabolite library (n = 494), a human metabolite library (n = 891) from epidemiological studies, and metabolite pharmacological databases to screen for food metabolites with potential bioactivity. We identified six potential metabolites, including meglutol (3-hydroxy-3-methylglutarate), an understudied low-density lipoprotein (LDL)-lowering compound. We further focused on meglutol as a case study to showcase the range of characterizations achievable with this approach. Green pea tempe was identified to contain the highest meglutol concentration (21.8 ± 4.6 mg/100 g). Furthermore, we identified a significant cross-sectional association between plasma meglutol (per 1-standard deviation) and lower LDL cholesterol in two Hispanic adult cohorts (n = 1,628) (β [standard error]: -5.5 (1.6) mg/dl, P = 0.0005). These findings highlight how multidisciplinary metabolomics can serve as a systematic tool for discovering and enhancing bioactive metabolites in food, such as meglutol, with potential applications in personalized dietary approaches for disease prevention.

Keywords: Bioactive compounds; Food metabolomics; Functional food; Meglutol; Molecular epidemiology.

MeSH terms

Cross-Sectional Studies
Humans
Indonesia
Meglutol* / metabolism
Meglutol* / pharmacology
Metabolomics
Soy Foods*

Substances

Meglutol