Ariaee, A. | Search bioRxiv

bioRxiv2026

Micro-engineered Konjac Glucomannan-Montmorillonite Hybrids as Multifunctional Biomaterials for Addressing Diet-Induced Obesity in Mice

The growing prevalence of obesity necessitates innovative treatments. This study investigates a spray-dried konjac glucomannan-montmorillonite (KGM-MMT) hybrid designed to combine the fermentable, satiety-promoting effects of KGM with the lipid-binding and anti-inflammatory properties of MMT. In HFD-fed mice treated for 42 days with 2% w/w KGM-MMT, body weight gain was reduced by 7.6%, with an AUC of 5094[{+/-}[52.95, compared to 5513[{+/-}[81.35 in HFD controls (p < 0.0001). Serum IL-6 concentrations were reduced by 97% (p = 0.0002), while blood glucose decreased by 46% (p < 0.0001), outperforming reductions seen with MMT (24%, p = 0.0271) and KGM (16%, ns). Gut microbiota profiling demonstrated a significant 6.2-log[ fold increase in Lactobacillaceae (p = 0.023) and a 2.4-log[ fold increase in Enterococcaceae (p = 0.015) with KGM-MMT treatment. Predicted functional shifts revealed a 1.9-fold increase in short-chain fatty acid synthesis pathways and a 5.4-fold increase in bile acid deconjugation. Although the KGM-MMT hybrid did not consistently outperform its individual components in all measurements within the current study, it generally consolidated their metabolic benefits within a single dosage form. These findings support the utility of spray-dried KGM-MMT as a gut-targeted dietary strategy with additive effects on metabolic health. Future studies should explore underlying mechanisms and dosage effects of the hybrid formulation. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/701163v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@738445org.highwire.dtl.DTLVardef@1f0d465org.highwire.dtl.DTLVardef@86e5aorg.highwire.dtl.DTLVardef@184fba8_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LISpray-dried KGM-MMT reduced HFD-induced weight gain by 7.6% in obese mice C_LIO_LISerum IL-6 and glucose levels decreased by 97% and 46%, respectively C_LIO_LI6.2-log[J and 2.4-log[J increases in Lactobacillaceae & Enterococcaceae relative abundance C_LIO_LIBile acid deconjugation and SCFA pathways increased 5.4- and 1.9-fold C_LIO_LIKGM-MMT microparticles offer additive gut-targeted benefits in metabolic disease C_LI

bioengineering↗

bioRxiv2026

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

bioengineering↗