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BIOACTIVE LIPIDS

How to irritate your host

Cell Host Microbe 25, 668–680 (2019)

Credit: Elsevier

Sphingolipids are bioactive signaling lipids that regulate various cellular processes such as inflammation and growth and have been implicated in associated diseases including inflammatory bowel disease (IBD). Sphingolipids are also a substantial component of the membrane of bacteria of the Bacteroidetes phylum, the only human gut commensal known to produce sphingolipids. To determine how Bacteroidetes sphingolipid production affects host metabolism and immunity during IBD, Brown et al. generated a Bacteroides thetaiotaomicron strain lacking the sphingolipid biosynthetic enzyme serine palmitoyltransferase (Spt). When introduced into germ-free mice, this sphingolipid-deficient strain led to intestinal inflammation, intestinal barrier dysfunction, and changes in host lipid metabolites (both sphingolipids and those not generated by Spt). Lipidomic analyses of mouse cecal extracts identified 35 unique Spt-dependent Bacteroides sphingolipids, including deoxysphinganine and ceramide phosphoinositol, and led the authors to propose an alternate sphingolipid biosynthesis pathway. The authors found that bacterial sphingolipids were inversely correlated with IBD and inflammation in a human cohort. These results define additional lipid products generated by Bacteroides Spt and define a role for Spt in both bacterial and host sphingolipid pathways.

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Correspondence to Mirella Bucci.

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Bucci, M. How to irritate your host. Nat Chem Biol 15, 651 (2019). https://doi.org/10.1038/s41589-019-0318-2

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