Abstract
Gut microbes are linked to host metabolism, but specific mechanisms remain to be uncovered. Ceramides, a type of sphingolipid (SL), have been implicated in the development of a range of metabolic disorders from insulin resistance (IR) to hepatic steatosis. SLs are obtained from the diet and generated by de novo synthesis in mammalian tissues. Another potential, but unexplored, source of mammalian SLs is production by Bacteroidetes, the dominant phylum of the gut microbiome. Genomes of Bacteroides spp. and their relatives encode serine palmitoyltransfease (SPT), allowing them to produce SLs. Here, we explore the contribution of SL-production by gut Bacteroides to host SL homeostasis. In human cell culture, bacterial SLs are processed by host SL-metabolic pathways. In mouse models, Bacteroides-derived lipids transfer to host epithelial tissue and the hepatic portal vein. Administration of B. thetaiotaomicron to mice, but not an SPT-deficient strain, reduces de novo SL production and increases liver ceramides. These results indicate that gut-derived bacterial SLs affect host lipid metabolism.
Highlights
Gut microbes are linked to host metabolism, but specific mechanisms remain to be uncovered
Bacteria-derived SLs have been shown to signal into inflammation-related pathways in the colon[21,22] but nothing is known about their ability to affect pathways involved in host lipid metabolism
To investigate the potential for bacterial SLs to influence host hepatic SL homeostasis, we first wanted to establish whether human epithelial cells could take up and process bacterial SLs
Summary
Gut microbes are linked to host metabolism, but specific mechanisms remain to be uncovered. Administration of B. thetaiotaomicron to mice, but not an SPT-deficient strain, reduces de novo SL production and increases liver ceramides These results indicate that gut-derived bacterial SLs affect host lipid metabolism. SLs are produced by gut bacteria of the phylum Bacteroidetes[17], including common genera (i.e., Bacteroides, Prevotella and Porphyromonas), that on average constitute ~30-40% of the human gut microbiome[17] These prominent members of the gut microbiome have the necessary enzyme serine palmitoyltransferase (SPT), which is responsible for the first step of de novo SL synthesis. In mice with diet-induced IR, administration of WT B. theta supplementation led to higher hepatic ceramide levels compared with the SPT-mutant Together, these findings indicate that Bacteroides-SLs produced in the gut provide an endogenous source of SLs that impacts host lipid homeostasis
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