Core Viewpoint - The article discusses the recent findings on the ketogenic diet, revealing its mechanisms for weight loss beyond traditional beliefs, particularly focusing on the role of specific bile acids and gut microbiota in reducing calorie absorption and promoting fat metabolism [6][7][15]. Group 1: Mechanisms of Ketogenic Diet - The ketogenic diet induces the production of ketone bodies, leading the body to utilize fat as an energy source, but recent studies show it also significantly increases energy expenditure [7]. - Research from Fudan University indicates that the ketogenic diet alters gut microbiota composition, reducing levels of bile salt hydrolase (BSH) and increasing levels of taurodeoxycholic acid (TDCA) and taurocholic acid (TUDCA), which inhibit calorie absorption [7][12]. - A clinical study involving over 400 participants confirmed that lower plasma levels of TDCA and TUDCA correlate with higher BMI and fasting blood glucose levels, suggesting these bile acids could be potential therapeutic targets for obesity [8][14]. Group 2: Experimental Findings - In a study with mice on a high-fat ketogenic diet (75.1% fat), significant weight loss and reduced fasting blood glucose were observed, alongside an increase in 22 metabolites, including six bile acids [11]. - The study found that TDCA and TUDCA significantly reduced body weight and improved glucose tolerance in normal diet mice, indicating their crucial role in the weight loss mechanism of the ketogenic diet [11][12]. - Analysis of gut microbiota revealed that specific strains, such as Lactobacillus murinus ASF361, significantly influence the levels of TDCA and TUDCA, thereby affecting weight and blood sugar levels [12][16]. Group 3: Clinical Implications - Participants in a 12-week ketogenic diet study lost an average of 5.27 kg, with significant increases in plasma TDCA and TUDCA levels, correlating with changes in BMI and fasting blood glucose [14]. - The findings support 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].

Core Viewpoint - The article discusses the rising popularity of ketogenic diets and presents new research findings that reveal the mechanisms behind weight loss associated with this diet, particularly focusing on the role of specific bile acids and gut microbiota [5][15]. Group 1: Mechanisms of Ketogenic Diet - Ketogenic diets induce the production of ketone bodies, prompting the body to utilize fat as an energy source, but recent studies indicate that the weight loss mechanisms are more complex [5]. - Research from Fudan University shows that ketogenic diets alter gut microbiota composition, leading to decreased levels of bile salt hydrolase (BSH), which results in increased levels of taurodeoxycholic acid (TDCA) and taurocholic acid (TUDCA) in the bloodstream [5][6]. - TDCA and TUDCA inhibit the expression of intestinal carbonic anhydrase 1, directly blocking calorie absorption [5][12]. Group 2: Clinical Observations and Findings - A clinical study involving over 400 participants confirmed the findings, suggesting that TDCA and TUDCA could serve as potential drug targets for treating obesity and its complications [6]. - In a 7-week study on mice fed a high-fat ketogenic diet (75.1% fat), significant reductions in body weight and fasting blood glucose were observed, alongside an increase in 22 metabolites, including six bile acids [9]. - The study also indicated that the presence of certain bile acids, particularly TDCA and TUDCA, plays a crucial role in the weight loss effects of the ketogenic diet [9][14]. Group 3: Gut Microbiota and Weight Loss - Analysis of the gut environment in mice revealed that the levels of TDCA and TUDCA are closely related to gut microbiota changes, with specific strains like Lactobacillus murinus ASF361 significantly impacting body weight and blood glucose levels [11][12]. - The study found that L. murinus ASF361 reduces serum levels of TDCA and TUDCA by metabolizing them into other bile acids, which suggests a complex interaction between diet, gut bacteria, and metabolic outcomes [12]. Group 4: Human Study Correlation - Data from 416 healthy participants indicated a correlation between low plasma levels of TDCA and TUDCA with high BMI and fasting blood glucose levels [14]. - Participants in a 12-week ketogenic diet study lost an average of 5.27 kg, with significant increases in plasma TDCA and TUDCA levels, aligning with findings from mouse experiments [14].