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Abstract:
Sphingolipids, a lipid class characterized by a long-chain amino alcohol backbone, serve vital structural and signaling roles in eukaryotes. Though eukaryotes produce sphingolipids, this capacity is phylogenetically highly restricted in Bacteria. Intriguingly, bacterial species commonly associated in high abundance with eukaryotic hosts include sphingolipid producers, such as the Bacteroidetes in the mammalian gut. A role for bacterial sphingolipids in immune system maturation has been described, but their fate and impact in host physiology and metabolism remain to be explored. Using germfree, low-germ and conventional mice on high or low soybean oil-content diet, we have shown that hepatic ceramide levels respond to gut microbial load, not dietary oil content. We mono-associated germfree mice with the human gut bacterium Bacteroides thetaiotaomicron, a sphingolipid producing bacterium, as either wildtype or a mutant strain deficient in its ability to produce sphingolipid. These experiments showed that hepatic ceramide levels were linked to the sphingolipid production capacity of the gut bacteria. In addition, we showed that gut bacterial lipids could translocate to the gut epithelium in vivo, and enter sphingolipid processing pathways in vitro. Together these findings indicate that lipids produced by gut bacteria can impact host lipid metabolic pathways.
