Abstract

Obesity is a global health crisis driven by complex metabolic dysregulation. Although Akkermansia muciniphila (AKK) has emerged as a promising next‐generation probiotic for metabolic health, its synergistic potential with natural anti‐obesity compounds remains largely unexplored. Here, we evaluated the combined administration of pasteurized A. muciniphila (AKM Lab‐01) and Garcinia cambogia extract (GCE) in a mouse model of high‐fat diet‐induced obesity. The combination treatment significantly ameliorated obesity‐related phenotypes, including reduced body weight, decreased fat mass, improved serum metabolic parameters, and attenuated adipose tissue inflammation. Adipose tissue transcriptomic profiling revealed enhanced lipid catabolism and downregulation of pro‐inflammatory pathways. Metagenomic sequencing showed marked gut microbiota remodeling, characterized by increased abundance of Lactococcus and decreased levels of Clostridium and Eisenbergiella . Integrated correlation analysis linked these microbial shifts to transcriptional reprogramming in adipose tissue. Using a 3 T3‐L1 adipocyte model, we further confirmed that Lactococcus plays a potential role in regulating lipid metabolism and inflammation. Collectively, these findings strongly suggest that the AKM Lab‐01 and GCE combination may exert synergistic anti‐obesity effects via a gut microbiota–host metabolic axis, supporting its potential as a novel synbiotic strategy for obesity management. Combined administration of pasteurized Akkermansia muciniphila (AKM Lab‐01) and Garcinia cambogia extract (GCE) alleviates high‐fat‐diet‐induced obesity in mice by reducing adiposity, metabolic disturbances, and adipose inflammation, while remodeling gut microbiota and adipose transcriptome, revealing a gut‐host metabolic axis that underpins the synergistic anti‐obesity efficacy.