Lactiplantibacillus plantarum Attenuates Diet‐Induced Obesity and Insulin Resistance Through Gut Microbiota‐Driven PPAR/PI3K ‐Axis Modulation

LPPerfectus001 (LPP; GDMCC 62334) is a strain isolated from traditional pickled vegetables and identified as Lactiplantibacillus plantarum by 16s rRNA sequencing and biochemical analysis. Whole-genome sequencing and functional prediction revealed that it is rich in carbohydrate metabolism and lipid metabolism genes, as well as short-chain fatty acid synthesis genes. Preliminary experiments on high-sugar and high-fat zebrafish showed that LPP has the potential to improve glucose and lipid metabolism. Subsequently, in a high-fat/high-fructose obese rat experiment, a 7-week intervention with LPP was conducted. Without altering energy intake, the high-dose LPP (LPPH) significantly reduced body weight and fat mass (p < 0.05), improved insulin sensitivity (reduced HOMA-IR and fasting blood glucose, p < 0.01) and normalised lipid profiles, thereby enhancing glucose homeostasis. This intervention reversed gut microbial dysbiosis by enriching beneficial bacteria (Akkermansia and Lactobacillus) and suppressing pathogens (Klebsiella pneumoniae and Ruminococcus), while also increasing short-chain fatty acids (butyrate/acetate) associated with improved metabolism. Transcriptome analysis revealed that LPPH remodelled adipose tissue through the PPAR signalling pathway (downregulating Pparg and upregulating Cpt1a) and activated the hepatic PI3K-Akt signalling pathway to enhance insulin sensitivity. These results suggest that LPPH alleviates metabolic disorders by synergistically regulating the gut microbiota-fat-liver axis (independent of appetite suppression), making it a promising probiotic therapy for the treatment of obesity-related metabolic disorders.