Core Viewpoint - The article discusses the rising popularity of the ketogenic diet and its mechanisms for weight loss, highlighting new research that reveals how this diet alters gut microbiota and affects bile acid levels, leading to reduced calorie absorption and potential therapeutic targets for obesity [6][15]. Group 1: Mechanisms of Ketogenic Diet - Traditional views suggest that the ketogenic diet induces ketone body production, prompting the body to use fat as an energy source. However, recent studies indicate that the weight loss mechanisms are more complex, including a significant increase in energy expenditure [7]. - Research from Fudan University reveals that the ketogenic diet alters specific gut microbiota, reducing bile salt hydrolase (BSH) levels, which leads to increased levels of taurodeoxycholic acid (TDCA) and taurocholic acid (TUDCA) in the bloodstream. These substances inhibit intestinal carbonic anhydrase 1 expression, directly blocking calorie absorption [7][11]. - A targeted metabolomics analysis of mice on a high-fat ketogenic diet showed a significant reduction in body weight and fasting blood glucose, with 22 metabolites elevated, including six bile acids. Notably, TDCA and TUDCA were found to play crucial roles in the weight loss mechanism [11][12]. Group 2: Clinical Observations and Implications - A clinical study involving over 400 participants confirmed that low plasma levels of TDCA and TUDCA correlate with high BMI and fasting blood glucose levels. Participants on a 12-week ketogenic diet lost an average of 5.27 kg, with significant increases in TDCA and TUDCA levels, aligning with findings from mouse experiments [8][14]. - The research supports the potential of TDCA and TUDCA as therapeutic targets for obesity and related metabolic diseases, providing a new perspective on the mechanisms of weight loss through the ketogenic diet [15]. - Further analysis of the gut environment in mice confirmed that changes in TDCA and TUDCA levels are closely related to gut microbiota, with gut microbiota transplants from ketogenic diet mice to recipient mice also resulting in weight loss [16].