Improving glucose tolerance in obese rats: the role of Jinlida granules ( ) in gut microbiota modulation.

OBJECTIVE: To investigate the effects of Jinlida granules (, JLD) on body weight, glucose tolerance, intestinal inflammation and barrier function in high-fat diet (HFD)-induced obese rats and explore the regulation of the gut microbiota as a potential treatment mechanism. METHODS: Sprague-Dawley rats were divided into control, HFD, low-dose JLD (L-JLD), high-dose JLD (H-JLD), and sitagliptin groups. The rats, with the exception of those in the control group, were fed a HFD to establish an obesity model while simultaneously receiving 0.5% carboxymethyl cellulose, L-JLD, H-JLD or sitagliptin for 25 weeks. We assessed body weight, conducted oral glucose tolerance tests, and analysed faecal samples using metagenomic sequencing. Haematoxylin-eosin (HE), Masson and immunohistochemical (IHC) staining were employed to evaluate histological changes in the colon tissue. Immunofluorescence (IF) staining was used to measure the expression levels of Zonula occludens-1 (ZO-1) and Claudin-1 in colon tissue. The colon tissue was also subjected to transcriptomic evaluation. RESULTS: JLD treatment significantly reduced body weight and enhanced glucose tolerance in obese rats. It alleviated colonic tissue damage, decreased collagen deposition, inhibited macrophage infiltration, and increased the expression of the tight junction proteins ZO-1 and Claudin-1. Metagenomic analysis revealed JLD-induced shifts in the gut microbiota composition (increasing the abundance of Turicibacter, Faecalibaculum, Coriobacteriaceae and Lactobacillus reuteri), enriching beneficial bacteria and metabolic pathways (increasing the biosynthesis of various secondary metabolites, ascorbate and aldarate metabolism, oxidative phosphorylation, C5-branched dibasic acid metabolism and beta-alanine metabolism). Transcriptomic analysis revealed downregulation of inflammatory and immune pathways (inhibition of the tumour necrosis factor signalling pathway, advanced glycation end products-receptor for advanced glycation end products signalling pathway, toll-like receptor signalling pathway, and interleukin-17 signalling pathway), suggesting a comprehensive modulatory effect of JLD on intestinal health and metabolic function. CONCLUSIONS: JLD granules effectively improve glucose tolerance and ameliorate obesity-related intestinal dysfunctions in HFD-induced obese rats. These benefits are likely mediated through the modulation of the gut microbiota, the suppression of intestinal inflammation, the enhancement of barrier function, and the attenuation of proinflammatory pathways. Our findings offer novel insights into the therapeutic potential of JLD, emphasizing its role in integrating gut microbiota management into the treatment of metabolic disorders.