Microbiome-metabolome dynamics associated with impaired glucose control and responses to lifestyle changes

Hao Wu; Bomin Lv; Luqian Zhi; Yikai Shao; Xinyan Liu; Matthias Mitteregger; Rima Chakaroun; Valentina Tremaroli; Stanley L Hazen; Ru Wang; Göran Bergström; Fredrik Bäckhed

doi:10.1038/s41591-025-03642-6

Microbiome-metabolome dynamics associated with impaired glucose control and responses to lifestyle changes

Nat Med. 2025 Apr 8. doi: 10.1038/s41591-025-03642-6. Online ahead of print.

Authors

Hao Wu¹, Bomin Lv², Luqian Zhi², Yikai Shao², Xinyan Liu², Matthias Mitteregger³, Rima Chakaroun^{3

4}, Valentina Tremaroli³, Stanley L Hazen^{5

6

7}, Ru Wang⁸, Göran Bergström^{3

9}, Fredrik Bäckhed^{10

11}

Affiliations

¹ Center for Obesity and Hernia Surgery, Department of General Surgery, Huashan Hospital, and State Key Laboratory of Genetic Engineering, Fudan Microbiome Center, Human Phenome Institute, Fudan University, Shanghai, China. hao_w@fudan.edu.cn.
² Center for Obesity and Hernia Surgery, Department of General Surgery, Huashan Hospital, and State Key Laboratory of Genetic Engineering, Fudan Microbiome Center, Human Phenome Institute, Fudan University, Shanghai, China.
³ The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁴ Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany.
⁵ Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland, OH, USA.
⁶ Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA.
⁷ Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA.
⁸ School of Kinesiology, Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, China.
⁹ Department of Clinical Physiology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
¹⁰ The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Fredrik@wlab.gu.se.
¹¹ Department of Clinical Physiology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden. Fredrik@wlab.gu.se.

PMID: 40200054
DOI: 10.1038/s41591-025-03642-6

Abstract

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.

Abstract

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