A fructo-oligosaccharide and sea buckthorn complex ameliorates glucose and lipid metabolism in type 2 diabetic (T2DM) rats via metabolic and anti-inflammatory pathways

Abstract

This study investigated the effects and underlying mechanisms of a fructo-oligosaccharide (FOS) and sea buckthorn complex (FS) on blood glucose and lipid metabolism in type 2 diabetic mellitus (T2DM) rats. The T2DM model was induced by a high-fat diet (HFD) combined with alloxan administration. Prior to rat experiments, the synergistic hypoglycemic and hypolipidemic effects of FOS and sea buckthorn have been verified by zebrafish experiments. FS intervention significantly reduced fasting blood glucose, triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in rats, although high-density lipoprotein cholesterol (HDL-C) showed a non-significant increasing trend. 16S rDNA sequencing revealed that FS significantly reshaped gut microbiota; it enriched beneficial genera (e.g., Akkermansia, Bifidobacterium) and suppressed inflammation-associated taxa (e.g., Escherichia–Shigella). Transcriptomic analysis indicated that FS reversed aberrant expression of inflammation-related genes (e.g., Retnlg, Retnlb, Bmp2 in the colon) and metabolism-related genes (e.g., Gpam, Cpt1a in the liver), activating pathways including fat digestion and absorption and fatty acid metabolism, while inhibiting immune-inflammatory pathways (e.g., the “TNF signaling pathway”, “Th17 cell differentiation”). Serum bile acid (BA) profiling showed FS modulated levels of primary and secondary BAs (e.g. CA, α-MCA, HDCA, GHDCA), restoring metabolic homeostasis. Pearson correlation analyses demonstrated robust associations among key microbiota, BAs, blood glucose/lipid indices, and farnesoid X receptor (FXR/Nr1h4) expression, supporting a regulatory network involving the gut–liver axis. This study elucidates the multi-target mechanisms by which FS ameliorates glucolipid metabolic disorders in T2DM, via gut microbiota remodeling, attenuation of intestinal/hepatic inflammation, and BA metabolism crosstalk, providing a theoretical basis for prebiotic-based precision nutrition.