Enzymatic synthesis of β-galactosylated xylitol derivatives modulates gut microbiota and improves obesity-related metabolic parameters in mice

Abstract

Obesity and its associated metabolic disorders are major global health concerns, highlighting the need for novel dietary interventions. Xylitol, a polyol widely used as a sugar substitute, has shown metabolic benefits beyond its sweetening properties. However, the potential physiological effects of its enzymatically modified derivatives, particularly β-galactosylated xylitol (XylGal), remain largely unexplored. In this study, we evaluated the impact of XylGal and unmodified xylitol (Xyl) on metabolic health and gut microbiota composition in a murine model of diet-induced obesity. Lean and obese C57BL/6J mice received daily doses of Xyl (50 mg kg⁻¹) or XylGal (50 and 100 mg kg⁻¹) for seven weeks. Our findings indicate that both Xyl and XylGal significantly reduced body weight gain, adipose tissue accumulation, and liver weight in obese mice, without affecting food intake. Additionally, Xyl and XylGal modulated glucose homeostasis, with Xyl-treated mice exhibiting improved glucose tolerance. A significant reduction in inflammatory cytokine expression (TNF-α, IL-1β) in abdominal fat was observed, suggesting decreased macrophage infiltration and attenuation of obesity-induced inflammation. High-throughput sequencing of 16S rRNA revealed that both compounds promoted beneficial bacterial genera, including Lachnospiraceae NK4A136 and Eubacterium xylanophilum, while reducing potentially obesity-associated taxa such as Blautia and Colidextribacter. These results suggest that XylGal and Xyl exert prebiotic effects that contribute to their metabolic benefits. Our study provides new insights into the potential of these compounds as functional ingredients for obesity management and metabolic health improvement.