Jardon Kelly M, Umanets Alexander, Gijbels Anouk, Trouwborst Inez, Hul Gabby B, Siebelink Els, Vliex Lars M M, Bastings Jacco J A J, Argamasilla Rosa, Chenal Elodie, Venema Koen, Afman Lydia A, Goossens Gijs H, Blaak Ellen E
TiFN, Wageningen, The Netherlands.
Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands.
Gut Microbes. 2025 Dec;17(1):2501185. doi: 10.1080/19490976.2025.2501185. Epub 2025 May 7.
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 ( = 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.
胰岛素抵抗（IR）是心脏代谢恶化的早期标志物，其可能在包括肝脏（LIR）和骨骼肌（MIR）在内的关键代谢器官中异质性发展。这种组织特异性IR具有独特的代谢特征，但其病因中肠道微生物群的作用仍不清楚。在此，我们对具有LIR或MIR表型（n = 233）的个体的肠道微生物群、其代谢产物和血浆代谢组进行了分析。我们观察到LIR和MIR具有不同的微生物群落结构，以及在LIR中产生短链脂肪酸（SCFA）的细菌、粪便SCFA和支链脂肪酸含量更高，且餐后血浆胰高血糖素样肽-1反应更强。此外，我们发现代谢组谱存在差异，以及微生物分类群与功能性代谢物组之间存在表型特异性关联。总体而言，我们的研究强调了肠道微生物群及其代谢物组成与IR异质性之间的关联，这可在基于精准的策略中作为靶点，以改善心脏代谢健康。Clinicaltrials.gov注册编号：NCT03708419。
