Distinct gut microbiota and metabolome features of tissue-specific insulin resistance in overweight and obesity

Kelly M. Jardon; Alexander Umanets; Anouk Gijbels; Inez Trouwborst; Gabby B. Hul; Els Siebelink; Lars M.M. Vliex; Jacco J.A.J. Bastings; Rosa Argamasilla; Elodie Chenal; Koen Venema; Lydia A. Afman; Gijs H. Goossens; Ellen E. Blaak

doi:10.1080/19490976.2025.2501185

Distinct gut microbiota and metabolome features of tissue-specific insulin resistance in overweight and obesity

Kelly M. Jardon, Alexander Umanets, Anouk Gijbels, Inez Trouwborst, Gabby B. Hul, Els Siebelink, Lars M.M. Vliex, Jacco J.A.J. Bastings, Rosa Argamasilla, Elodie Chenal, Koen Venema, Lydia A. Afman, Gijs H. Goossens, Ellen E. Blaak^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

4 Citations (Scopus)

Abstract

Insulin resistance (IR) is an early marker of cardiometabolic deterioration which may develop heterogeneously in key metabolic organs, including the liver (LIR) and skeletal muscle (MIR). This tissue-specific IR is characterized by distinct metabolic signatures, but the role of the gut microbiota in its etiology remains unclear. Here, we profiled the gut microbiota, its metabolites and the plasma metabolome in individuals with either a LIR or MIR phenotype (n = 233). We observed distinct microbial community structures LIR and MIR, and higher short-chain fatty acid (SCFA) producing bacteria, fecal SCFAs and branched-chain fatty acids and a higher postprandial plasma glucagon-like-peptide-1 response in LIR. In addition, we found variations in metabolome profiles and phenotype-specific associations between microbial taxa and functional metabolite groups. Overall, our study highlights association between gut microbiota and its metabolites composition with IR heterogeneity that can be targeted in precision-based strategies to improve cardiometabolic health. Clinicaltrials.gov registration: NCT03708419.

Original language	English
Article number	2501185
Journal	Gut Microbes
Volume	17
Issue number	1
DOIs	https://doi.org/10.1080/19490976.2025.2501185
Publication status	Published - 7 May 2025

Keywords

GLP-1
gut metabolites
gut microbiota
metabolic subtyping
precision health
Tissue-specific insulin resistance: obesity

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/19490976.2025.2501185Licence: CC BY

https://edepot.wur.nl/693300Licence: CC BY

PERSonalized glucose Optimization through Nutritional intervention
Jardon, K. M. (Creator), Umanets, A. (Creator), Gijbels, A. (Creator), Trouwborst, I. (Creator), Hul, G. B. (Creator), Siebelink, E. (Creator), Vliex, L. M. M. (Creator), Bastings, J. J. A. J. (Creator), Argamasilla, R. (Creator), Chenal, E. (Creator), Venema, K. (Creator), Afman, L. A. (Creator), Goossens, G. H. (Creator) & Blaak, E. E. (Creator), Universiteit Maastricht, 1 Sept 2023
https://www.ncbi.nlm.nih.gov/bioproject/1011518
Dataset

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Jardon, K. M., Umanets, A., Gijbels, A., Trouwborst, I., Hul, G. B., Siebelink, E., Vliex, L. M. M., Bastings, J. J. A. J., Argamasilla, R., Chenal, E., Venema, K., Afman, L. A., Goossens, G. H., & Blaak, E. E. (2025). Distinct gut microbiota and metabolome features of tissue-specific insulin resistance in overweight and obesity. Gut Microbes, 17(1), Article 2501185. https://doi.org/10.1080/19490976.2025.2501185

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abstract = "Insulin resistance (IR) is an early marker of cardiometabolic deterioration which may develop heterogeneously in key metabolic organs, including the liver (LIR) and skeletal muscle (MIR). This tissue-specific IR is characterized by distinct metabolic signatures, but the role of the gut microbiota in its etiology remains unclear. Here, we profiled the gut microbiota, its metabolites and the plasma metabolome in individuals with either a LIR or MIR phenotype (n = 233). We observed distinct microbial community structures LIR and MIR, and higher short-chain fatty acid (SCFA) producing bacteria, fecal SCFAs and branched-chain fatty acids and a higher postprandial plasma glucagon-like-peptide-1 response in LIR. In addition, we found variations in metabolome profiles and phenotype-specific associations between microbial taxa and functional metabolite groups. Overall, our study highlights association between gut microbiota and its metabolites composition with IR heterogeneity that can be targeted in precision-based strategies to improve cardiometabolic health. Clinicaltrials.gov registration: NCT03708419.",

keywords = "GLP-1, gut metabolites, gut microbiota, metabolic subtyping, precision health, Tissue-specific insulin resistance: obesity",

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Jardon, KM, Umanets, A, Gijbels, A, Trouwborst, I, Hul, GB, Siebelink, E, Vliex, LMM, Bastings, JJAJ, Argamasilla, R, Chenal, E, Venema, K , Afman, LA, Goossens, GH & Blaak, EE 2025, 'Distinct gut microbiota and metabolome features of tissue-specific insulin resistance in overweight and obesity', Gut Microbes, vol. 17, no. 1, 2501185. https://doi.org/10.1080/19490976.2025.2501185

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T1 - Distinct gut microbiota and metabolome features of tissue-specific insulin resistance in overweight and obesity

AU - Jardon, Kelly M.

AU - Umanets, Alexander

AU - Gijbels, Anouk

AU - Trouwborst, Inez

AU - Hul, Gabby B.

AU - Siebelink, Els

AU - Vliex, Lars M.M.

AU - Bastings, Jacco J.A.J.

AU - Argamasilla, Rosa

AU - Chenal, Elodie

AU - Venema, Koen

AU - Afman, Lydia A.

AU - Goossens, Gijs H.

AU - Blaak, Ellen E.

PY - 2025/5/7

Y1 - 2025/5/7

N2 - Insulin resistance (IR) is an early marker of cardiometabolic deterioration which may develop heterogeneously in key metabolic organs, including the liver (LIR) and skeletal muscle (MIR). This tissue-specific IR is characterized by distinct metabolic signatures, but the role of the gut microbiota in its etiology remains unclear. Here, we profiled the gut microbiota, its metabolites and the plasma metabolome in individuals with either a LIR or MIR phenotype (n = 233). We observed distinct microbial community structures LIR and MIR, and higher short-chain fatty acid (SCFA) producing bacteria, fecal SCFAs and branched-chain fatty acids and a higher postprandial plasma glucagon-like-peptide-1 response in LIR. In addition, we found variations in metabolome profiles and phenotype-specific associations between microbial taxa and functional metabolite groups. Overall, our study highlights association between gut microbiota and its metabolites composition with IR heterogeneity that can be targeted in precision-based strategies to improve cardiometabolic health. Clinicaltrials.gov registration: NCT03708419.

AB - Insulin resistance (IR) is an early marker of cardiometabolic deterioration which may develop heterogeneously in key metabolic organs, including the liver (LIR) and skeletal muscle (MIR). This tissue-specific IR is characterized by distinct metabolic signatures, but the role of the gut microbiota in its etiology remains unclear. Here, we profiled the gut microbiota, its metabolites and the plasma metabolome in individuals with either a LIR or MIR phenotype (n = 233). We observed distinct microbial community structures LIR and MIR, and higher short-chain fatty acid (SCFA) producing bacteria, fecal SCFAs and branched-chain fatty acids and a higher postprandial plasma glucagon-like-peptide-1 response in LIR. In addition, we found variations in metabolome profiles and phenotype-specific associations between microbial taxa and functional metabolite groups. Overall, our study highlights association between gut microbiota and its metabolites composition with IR heterogeneity that can be targeted in precision-based strategies to improve cardiometabolic health. Clinicaltrials.gov registration: NCT03708419.

KW - GLP-1

KW - gut metabolites

KW - gut microbiota

KW - metabolic subtyping

KW - precision health

KW - Tissue-specific insulin resistance: obesity

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DO - 10.1080/19490976.2025.2501185

M3 - Article

AN - SCOPUS:105004477179

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JO - Gut Microbes

JF - Gut Microbes

IS - 1

M1 - 2501185

ER -

Distinct gut microbiota and metabolome features of tissue-specific insulin resistance in overweight and obesity

Abstract

Keywords

UN SDGs

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Datasets

PERSonalized glucose Optimization through Nutritional intervention

Cite this