Lithocholic Acid Improves the Survival of Drosophila Melanogaster

Scope: Primary bile acids are produced in the liver, whereas secondary bile acids, such as lithocholic acid (LCA), are generated by gut bacteria from primary bile acids that escape the ileal absorption. Besides their well-known function as detergents in lipid digestion, bile acids are important signaling molecules mediating effects on the host's metabolism. Methods and results: Fruit flies (Drosophila melanogaster) are supplemented with 50 μmol L^–1 LCA either for 30 days or throughout their lifetime. LCA supplementation results in a significant induction of the mean (+12 days), median (+10 days), and maximum lifespan (+ 11 days) in comparison to untreated control flies. This lifespan extension is accompanied by an induction of spargel (srl), the fly homolog of mammalian PPAR-γ co-activator 1α (PGC1α). In wild-type flies, the administration of antibiotics abrogates both the LCA-mediated lifespan induction as well as the upregulation of srl. Conclusion: It is shown that the secondary bile acid LCA significantly induces the mean, the median, and the maximum survival in D. melanogaster. Our data suggest that besides an upregulation of the PGC1α-homolog srl, unidentified alterations in the structure or metabolism of the gut microbiota contribute to the longevity effect mediated by LCA.