๐ก This study presents groundbreaking insights into the strain-specific modulation of human gut microbiota on lipid homeostasis, focusing on the identification of microbial strains with potent lipid-decreasing activities. The study employs a multidisciplinary approach, integrating pharmacology, genomics, and metabolomics, to identify the key active metabolite responsible for Bl.
๐ Hyperlipidemia, a prevalent metabolic disorder worldwide, is associated with severe health implications such as cardiovascular diseases and nonalcoholic fatty liver disease.
๐ Methods: The research employs a large-scale cellular screening approach, assessing lipid-decreasing activities of 2250 human gut bacterial strains across 186 species. Strain-specificity is emphasized, revealing distinct lipid-modulatory actions even within the same species. ๐๐ญ๐ข๐ถ๐ต๐ช๐ข ๐ฑ๐ณ๐ฐ๐ฅ๐ถ๐ค๐ต๐ข emerges as the most potent strain in suppressing cellular lipid accumulation.
๐ Key Findings:
๐ Strain-Specific Lipid Modulation: The study uncovers a previously unreported strain-specific profile of lipid-modulatory capacities among human gut microbial strains.
๐ Blautia producta as a Key Player: ๐๐ญ๐ข๐ถ๐ต๐ช๐ข ๐ฑ๐ณ๐ฐ๐ฅ๐ถ๐ค๐ต๐ข, a member of the Blautia genus with potential probiotic properties, is identified as a promising anti-hyperlipidemic agent. It robustly decreases lipid accumulation, rivaling the efficacy of fenofibrate, a positive control drug.
๐ Identification of Active Metabolite – 12-Methylmyristic Acid (12-MMA): Through a joint approach of pharmacology, genomics, and metabolomics, 12-MMA is identified as the crucial metabolite responsible for ๐๐ญ๐ข๐ถ๐ต๐ช๐ข ๐ฑ๐ณ๐ฐ๐ฅ๐ถ๐ค๐ต๐ข anti-hyperlipidemic effects.
๐ In Vivo Efficacy: ๐๐ญ๐ข๐ถ๐ต๐ช๐ข ๐ฑ๐ณ๐ฐ๐ฅ๐ถ๐ค๐ต๐ข and its active metabolite, 12-MMA, demonstrate efficacy in ameliorating hyperlipidemia in high-fat diet-fed mice. The anti-hyperlipidemic effects include decreased body weight gain, lower serum lipid levels, and alleviated liver steatosis.
๐ Activation of GPR120: 12-MMA is shown to activate G protein-coupled receptor 120 (GPR120), suggesting a potential mechanism for its anti-hyperlipidemic activity. This activation leads to thermogenic effects, white adipose tissue browning, and improved glucose metabolism.
๐ Implications: This study sheds light on the strain-level diversity within human gut microbiota and its profound impact on host lipid metabolism. The identification of ๐๐ญ๐ข๐ถ๐ต๐ช๐ข ๐ฑ๐ณ๐ฐ๐ฅ๐ถ๐ค๐ต๐ข and its metabolite, 12-MMA, opens avenues for the development of microbial therapeutics against hyperlipidemia. The findings emphasize the importance of conducting microbial studies at the strain level for accurate therapeutic interventions.
Link to the article : http://tinyurl.com/mr295cnm
