The ketogenic diet (KD), known for its low-carbohydrate and high-fat composition, has been utilized for weight loss, yet its exact mechanisms remain unclear. Recent research highlights the role of bile acids, particularly taurodeoxycholic acid (TDCA) and tauroursodeoxycholic acid (TUDCA), in mediating the metabolic effects of KD consumption. These bile acids have shown promise in reducing body weight and improving glucose metabolism by altering gut microbiota composition and inhibiting specific microbial enzymes.
Key Findings
Enhanced Bile Acid Levels: KD consumption in mice increases serum levels of TDCA and TUDCA. These bile acids contribute to decreased body weight and fasting glucose levels.
Microbial Mechanisms: KD reduces the abundance of Lactobacillus murinus ASF361, a bacterium encoding bile salt hydrolase (BSH). This reduction leads to elevated levels of TDCA and TUDCA in circulation.
Impact on Energy Absorption: Elevated TDCA and TUDCA levels inhibit intestinal carbonic anhydrase 1 expression, reducing energy absorption and promoting weight loss.
Human Studies: Observational and interventional studies in humans (416 healthy participants and 25 overweight or obese participants on KD) confirm associations between bile acids, microbial BSH activity, and metabolic traits like obesity and glucose metabolism.
Implications
Therapeutic Potential: TDCA and TUDCA emerge as potential therapeutic agents for obesity and related metabolic disorders, beyond their role in KD.
Mechanistic Insight: The study underscores the intricate metabolic interactions between host and gut microbiota, elucidating how dietary interventions like KD influence metabolic health through bile acid modulation.
Data Availability
Access: Raw data from the study, including serum metabolomic, metagenomic, and intestinal transcriptome data from animal models, as well as human study data, are accessible through NODE.
Data Sharing: De-identified data can be obtained upon formal request and appropriate approvals from the Oversight Group of the respective cohorts.
Conclusion
This study reveals a novel metabolic mechanism where KD-induced alterations in bile acid profiles, influenced by gut microbiota changes, contribute to weight loss and improved glucose metabolism. TDCA and TUDCA are highlighted as potential therapeutic targets, offering new avenues for combating obesity and its associated health risks. These findings provide valuable insights into personalized dietary strategies and drug development for metabolic disorders.