Microbiome–metabolome dynamics associated with impaired glucose control and responses to lifestyle changes
Type 2 diabetes (T2D) is a complex disease shaped by genetic and environmental factors, including the gut microbiome. Recent research revealed pathophysiological heterogeneity and distinct subgroups in both T2D and prediabetes, prompting exploration of personalized risk factors. Using metabolomics in two Swedish cohorts (n = 1,167), we identified over 500 blood metabolites associated with impaired glucose control, with approximately one-third linked to an altered gut microbiome. Our findings identified metabolic disruptions in microbiome-metabolome dynamics as potential mediators of compromised glucose homeostasis, as illustrated by the potential interactions between Hominifimenecus microfluidus and Blautia wexlerae via hippurate. Short-term lifestyle changes, for example, diet and exercise, modulated microbiome-associated metabolites in a lifestyle-specific manner. This study suggests that the microbiome-metabolome axis is a modifiable target for T2D management, with optimal health benefits achievable through a combination of lifestyle modifications.
Authors
- Bo‐Min Lv
- Göran M.L. Bergström (ORCID: https://orcid.org/0000-0003-4289-5722)
- Matthias Mitteregger (ORCID: https://orcid.org/0000-0002-0703-6415)
- Stanley L. Hazen (ORCID: https://orcid.org/0000-0001-7124-6639)
- Fredrik Bäckhed (ORCID: https://orcid.org/0000-0002-4871-8818)
- Rima Chakaroun (ORCID: https://orcid.org/0000-0001-9901-1815)
- Valentina Tremaroli (ORCID: https://orcid.org/0000-0002-9150-4233)
- Hao Wu (ORCID: https://orcid.org/0000-0003-1314-4954)
- Ru Wang (ORCID: https://orcid.org/0000-0003-1064-9615)
- Luqian Zhi
- Yikai Shao
- Xinyan Liu
Institutions
- Cleveland Clinic (US)
- Shanghai University of Sport (CN)
- Fudan University (CN)
- Sahlgrenska University Hospital (SE)
- Cleveland Clinic Lerner College of Medicine (US)
- Region Västra Götaland (SE)
- Huashan Hospital (CN)
- University of Gothenburg (SE)
Publication Details
- Journal
- Nature Medicine
- Published
- 2025-04-08
- DOI
- https://doi.org/10.1038/s41591-025-03642-6
- Citations
- 35
- Primary Topic
- Metabolomics and Mass Spectrometry Studies
- Type
- article
- Field-Weighted Citation Impact
- 28.21
Funders
- Wellcome Trust
- National Institute for Health and Care Research
- King's College London
- European Commission
- Deutsche Forschungsgemeinschaft
- Fondation Leducq
- National Natural Science Foundation of China
- VINNOVA
- Shanghai University of Sport
- Fudan University
- Hjärt-Lungfonden
- Knut och Alice Wallenbergs Stiftelse
- Novo Nordisk
- Vetenskapsrådet
- Göteborgs Universitet
- Diabetesfonden
- Novo Nordisk Fonden
- Versus Arthritis
- Higher Education Discipline Innovation Project
- Medical Research Council
- Uppsala Multidisciplinary Center for Advanced Computational Science