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 Highlights Spray-dried KGM-MMT reduced HFD-induced weight gain by 7.6% in obese mice Serum IL-6 and glucose levels decreased by 97% and 46%, respectively 6.2-log[J and 2.4-log[J increases in Lactobacillaceae & Enterococcaceae relative abundance Bile acid deconjugation and SCFA pathways increased 5.4- and 1.9-fold KGM-MMT microparticles offer additive gut-targeted benefits in metabolic disease