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Chakaroun, R.M.* ; Pradhan, M.* ; Björnson, E.* ; Arvidsson, D.* ; Fridolfsson, J.* ; Gummesson, A.* ; Schoeler, M.* ; Mitteregger, M.* ; Smith, G.J.* ; Larsson, I.* ; Börjesson, M.* ; Blüher, M. ; Uhlén, M.* ; Stumvoll, M. ; Bergström, G.* ; Tremaroli, V.* ; Bäckhed, F.*

Multi-omic definition of metabolic obesity through adipose tissue-microbiome interactions.

Nat. Med. 32, 113-125 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Obesity's metabolic heterogeneity is not fully captured by body mass index (BMI). Here we show that deep multi-omics phenotyping of 1,408 individuals defines a metabolome-informed obesity metric (metBMI) that captures adipose tissue-related dysfunction across organ systems. In an external cohort (n = 466), metBMI explained 52% of BMI variance and more accurately reflected adiposity than other omics models. Individuals with higher-than-expected metBMI had 2-5-fold higher odds of fatty liver disease, diabetes, severe visceral fat accumulation and attenuation, insulin resistance, hyperinsulinemia and inflammation and, in bariatric surgery (n = 75), achieved 30% less weight loss. This obesogenic signature aligned with reduced microbiome richness, altered ecology and functional potential. A 66-metabolite panel retained 38.6% explanatory power, with 90% covarying with the microbiome. Mediation analysis revealed a bidirectional, metabolite-centered host-microbiome axis, mediated by lipids, amino acids and diet-derived metabolites. These findings define an adipose-linked, microbiome-connected metabolic signature that outperforms BMI in stratifying cardiometabolic risk and guiding precision interventions.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Insulin-resistance; Glucose; Risk
ISSN (print) / ISBN 1078-8956
e-ISSN 1546-170X
Journal Nature medicine
Quellenangaben Volume: 32, Issue: 1, Pages: 113-125 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Grants Hjrt-Lungfonden (Swedish Heart-Lung Foundation)
Diabetesfonden (Stiftelsen Svenska Diabetesfrbundets Forskningsfond)
Deutsche Forschungsgemeinschaft (German Research Foundation)
Fondation Leducq
Vetenskapsrdet (Swedish Research Council)
Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)
Novo Nordisk Fonden (Novo Nordisk Foundation)