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제주대학교

Phytomedicine, Available online 12 June 2026 | https://doi.org/10.1016/j.phymed.2026.158423 Medium-chain inulin reshapes the gut microbiome-metabolome axis to counteract high-fat diet-induced obesity

Yunpeng Wang ^a,b†, Eunyoung Kim ^b,c†, Jiamei Cui ^a,b, Yunkyoung Lee ^b,c, Guiguo Zhang^a,b,d

^aDepartment of Nutrition, Shandong Agricultural University, Taian City 271018, PR China
^bChina-South Korea International Joint Laboratory of Functional Polysaccharides in Shandong Province, Taian City 271018, PR China
^cDepartment of Food Science and Nutrition, Jeju National University, Jeju 63243, Republic of Korea
^dKey Laboratory of Efficient Utilization of Non-grain Feed Resources, Taian City 271018, PR China

^†These authors contributed equally to this study and shared first authorship.
Corresponding authors: Yunkyoung Lee, Guiguo Zhang

Abstract

Background
Inulin, a natural dietary fiber, exerts diverse health benefits that are closely linked to its molecular structure. However, the biological activity of medium-chain inulin and its role in high-fat diet (HFD)-induced obesity remain poorly characterized.

Objective
This study aimed to determine whether medium-chain inulin could alleviate high-fat diet (HFD)-induced obesity by modulating the gut microbiota and metabolome, thereby restoring metabolic homeostasis.

Methods
Forty male C57BL/6 mice were fed either a standard chow diet or an HFD with 1%, 3%, or 5% medium-chain inulin (average degree of polymerization = 12) for 12 weeks. Body weight (BW), physiological indices, gut microbiota, and metabolome were analyzed to elucidate the underlying mechanisms. Short-chain fatty acids (SCFAs) were quantified by gas chromatography. Cecal microbiota and metabolome were analyzed using 16S rRNA sequencing and LC–MS/MS, respectively. Correlation and pathway analyses were conducted to identify key microbe–metabolite interactions.

Results
Medium-chain inulin supplementation significantly reduced BW gain (by 16% and 20% at 3% and 5% doses, respectively), increased acetic and butyric acid levels, and improved serum and hepatic lipid profiles. It reshaped the gut microbiota by enriching Faecalibaculum, Bifidobacterium, Parasutterella, Clostridium_sensu_stricto_1, Bacteroides, Lactobacillus, and Akkermansia. Metabolomic analysis revealed elevated levels of eight key metabolites related to tryptophan metabolism and bile acid metabolism, correlating with improved metabolic indicators.

Conclusion
Medium-chain inulin alleviated HFD-induced obesity by remodeling the gut microbiome-metabolome axis and promoting SCFA production. These findings highlight its potential as a functional prebiotic candidate for obesity-related metabolic disorders.

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