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Zusammenfassung:
Sphingolipidproducing Bacteroides spp. are variably abundant in the human gut microbiome, with an average abundance of 4060% in Western populations. The gastrointestinal tracts of individuals colonized by these bacteria are continuously dosed with these bacterial lipids, with potential effects on host immunity and metabolism. Yet, the enzymes responsible for bacterial sphingolipid synthesis remain largely unknown, with the major exception of serine palmitoyltransferase (SPT), which performs the initial step of de novo sphingolipid synthesis and is conserved across kingdoms. Here, we have placed SPT under inducible control in Bacteroides thetaiotaomicron, a prominent member of the human gut microbiome. By performing RNAseq at varied levels of SPTinduction (hence at varied levels of sphingolipid synthesis), we have identified alterations to gene expression profiles to find novel enzymes involved in bacterial sphingolipid metabolism. The elucidation of the central bacterial sphingolipid metabolic pathway will help advance the development of bacterial sphingolipids as therapeutics for improving host immune and metabolicrelated outcomes.