Spray Dried Inulin-Montmorillonite Hybrids Alleviate High-Fat Diet-Induced Inflammatory and Metabolic Dysregulation in Rats

Obesity-related metabolic disorders are linked to excessive dietary lipid absorption and gut microbiota imbalances, particularly under high-fat diet (HFD) conditions. This study evaluates a spray-dried hybrid of inulin and montmorillonite (INU-MMT) designed to concurrently restrict intestinal lipid digestion and modulate the gut microbiota. Using an in vitro simulated intestinal lipolysis model, INU-MMT significantly reduced free fatty acid (FFA) release from medium-chain triglycerides by 4.0-fold compared to HFD conditions, outperforming INU and MMT individually. This superior inhibition is attributed to INUs ability to prevent MMT aggregation, resulting in smaller, more dispersed particles with enhanced lipid-binding capacity. In a 21-day in vivo study in HFD-fed rats, INU-MMT (1g/kg bodyweight/d) supplementation significantly attenuated cumulative weight gain by 4.7% compared to the HFD control, exceeding the effects of INU (2.0%) and MMT (1.5%) alone. 16S rRNA gene sequencing of fecal samples revealed improved gut microbial diversity (Simpsons index, p = 0.0161) and enrichment of health-associated taxa including Peptostreptococcaceae (8-fold), Ruminococcaceae (3.5-fold), Akkermansiaceae (2.5-fold), and Eggerthellaceae (7.7-fold). Beta diversity analysis highlighted that INU-MMT induced a distinct microbial composition from HFD and INU groups (PERMANOVA, adjusted p < 0.05), driven largely by MMT. Predictive metagenomic analysis using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2 (PICRUSt2) software demonstrated a 98% reduction in microbial triacylglycerol lipase abundance, aligning with the observed in vitro lipolysis suppression results. These findings highlight the dual-mechanistic potential of INU-MMT in managing diet-induced obesity by targeting lipid digestion and imbalances within the gut microbiota. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/701174v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@1d2c787org.highwire.dtl.DTLVardef@1298bacorg.highwire.dtl.DTLVardef@90da36org.highwire.dtl.DTLVardef@1e6271c_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LISpray-dried INU-MMT restricts FFA release 4-fold in intestinal conditions C_LIO_LIHybrid outperforms INU and MMT in reducing HFD-induced weight gain in rats C_LIO_LIPromotes beneficial microbiota shifts and key SCFA-producing taxa C_LIO_LISuppressed predicted microbial lipase levels by 98% with INU-MMT treatment C_LIO_LIINU-MMT offers a multi-mechanistic strategy for future metabolic disease therapies. C_LI