Combined Use of Tryptophan and Fu Brick Tea in Low Doses Promotes Weight Loss in Mice by Modulating AhR-Mediated Tryptophan Metabolism and Reshaping the Gut Microbiota

Fu brick tea (FBT) combats obesity by modulating gut microbiota, while tryptophan (Trp) lacks direct effects but exerts anti-obesity potential via microbiota-derived metabolites. However, their synergistic anti-obesity effect remains unclear. We demonstrated that low-dose FBT extract (FTE) combined with free Trp or Trp-bound proteins from soy protein isolate and sheep whey protein produced synergistic antiobesity effects in high-fat diet-induced mice. Trp+FTE effectively combated obesity, reducing weight and fat, while alleviating inflammation and hepatocellular steatosis. Further mechanistic analyses showed that Trp+FTE alleviated obesity by tissue-specific regulation of aryl hydrocarbon receptor (AhR) signaling, modulation of Trp metabolic pathways, reshaping gut microbiota composition, and increasing short-chain fatty acid production. Metabolomic profiling further revealed coordinated alterations in amino acid and lipid metabolism, accompanied by elevated levels of beneficial Trp-derived metabolites in peripheral tissues. Collectively, these findings suggest that the synergistic effects are driven by coordinated regulation of AhR-mediated Trp metabolism and gut microbiota modulation.