Regulatory Effect of Isomaltodextrin on a High-Fat Diet Mouse Model with LPS-Induced Low-Grade Chronic Inflammation.

This study aimed to identify the effects of isomaltodextrin (IMD) on sustaining the gut integrity and microbiota composition in a high-fat diet (HFD) with a lipopolysaccharide (LPS)-induced low-grade inflammation mouse model. The homeostasis of the immune response is important to reduce the risk of developing metabolic syndromes. The results of this study showed that pre-treatment of IMD at 5% (w/v) suppressed the concentration of endotoxin and pro-inflammatory mediators TNF-α, MCP-1, and IL-6 while increasing the adiponectin level in the plasma. Subsequently, IMD supplementation maintained the structural integrity and intestinal permeability by upregulating the tight junction protein expressions, leading to reducing D-mannitol concentration in the blood. In addition, dysbiosis was observed in mice induced by HFD plus LPS, suggesting that unhealthy dietary factors elicit metabolic endotoxemia and associated dysbiosis to impair the barrier function. However, IMD supplementation was shown to restore the microbial diversity, promote the growth of Bacteroides-Prevotella , and upregulate the related d-glucarate and d-galactarate degradation pathways, together demonstrating the benefits of IMD as a prebiotic able to promote energy homeostasis. Our results also showed that the blood lipid profile and glucose level in the low-grade inflammation mouse model were modulated by IMD. Moreover, IMD supplementation effectively prevented the metabolic disorder and modulated immune responses in inflamed white adipose tissues by inhibiting the macrophage infiltration and restoring the adiponectin, PPAR-γ, and IRS-1 expression. These findings provide strong evidence for IMD to be a potential prebiotic that acts to sustain a healthy gut microbiota composition and barrier function. By protecting against an unhealthy diet-impaired metabolic balance and maintaining immune homeostasis, IMD may affect the development of metabolic disorders.