Combined Oat β-Glucan and Soy Protein Isolate Reprogram Gut Microbiota and Improve Metabolic Dysfunction in Diet-Induced Obesity

Background/Objectives: Although plant-derived dietary fiber and protein are favorable factors for improving host metabolic disorders, it remains unclear whether these two macronutrients exhibit synergistic health benefits. Methods: To address this gap, utilizing oat dietary fiber (GLU) and soybean protein (SBP) as representative bioactive models, we investigated the effects of 5% GLU, 20% SBP, and their combined supplementation on high-fat diet (HFD)-induced metabolic dysregulation in C57BL/6J mice. Results: Our results demonstrated that the combined GLU + SBP intervention provided comprehensive protection against HFD-induced obesity, significantly attenuating body weight gain (12.29 ± 2.02 g vs. 21.90 ± 2.86 g, p < 0.05) and adiposity (3.34 ± 1.19% vs. 10.77 ± 1.16%, p < 0.05) compared with HFD mice, without altering caloric intake. Crucially, the compound formulation exhibited synergistic superiority over individual components, as evidenced by greater reductions in serum aspartate aminotransferase (AST) activity (113.13 ± 28.50 U/L vs. 158.00 ± 30.25 U/L, p < 0.05) and improved glucose tolerance, with lower OGTT AUC values (999.09 ± 95.83 vs. 1434.66 ± 80.56 mmol/L·min, p < 0.05). Mechanistically, 16S rRNA sequencing revealed a distinct remodeling of the gut microbial community, highlighted by a substantial enrichment of Akkermansia. Functional prediction analysis specifically linked this microbial shift to the modulation of Akkermansia-associated metabolic pathways, which subsequently facilitated the activation of host metabolic networks to combat lipid deposition and systemic metabolic stress. Conclusions: Collectively, the GLU + SBP combination offers synergistic metabolic benefits driven by a distinct gut microbiota signature, supporting a feasible “soluble fiber + plant protein” strategy for developing functional foods targeting metabolic health.