D-Tagatose ameliorates diet-induced glucose and lipid metabolic dysfunction by reshaping gut microbiota and restoring metabolic homeostasis.

Obesity is a major global health concern that significantly increases the risk of chronic metabolic diseases, including type 2 diabetes and cardiovascular diseases. This study investigated the ameliorative effects of D-tagatose on glucose and lipid metabolic disorders induced by a high-fat and high-sucrose diet (HFHSD) in obese rats, and systematically explored the underlying mechanisms through a combination of biochemical, histopathological, gut microbiomic, and serum metabolomic analyses. The results demonstrated that D-tagatose significantly suppressed body weight gain and fat accumulation. Compared with the control group, the HFHSD induced pronounced glucose and lipid metabolic disorders. Compared with the HFHSD group, D-tagatose ameliorated these abnormalities: it significantly reduced fasting insulin (FINS) and the insulin resistance index (IRI), increased the insulin sensitivity index (ISI), lowered serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), and elevated high-density lipoprotein cholesterol (HDL-C). D-Tagatose also mitigated oxidative stress and liver injury and attenuated systemic inflammation. D-Tagatose effectively prevented hepatic injury and visceral fat accumulation. Specifically, D-tagatose reshaped the gut microbial composition, promoting beneficial bacteria such as Lactobacillus, Bifidobacterium, and Lachnospiraceae_NK4A136_group while suppressing harmful bacteria including Alistipes and Colidextribacter. Metabolomic profiling further demonstrated that D-tagatose regulated key metabolites involved in amino acid and lipid metabolism pathways. Collectively, D-tagatose exerts its protective effects against HSHFD-induced metabolic disorders through the gut microbiota-metabolism axis, highlighting its potential as a functional food ingredient for the prevention and improvement of obesity-associated metabolic diseases.