Gut bacterial sphingolipid production modulates dysregulated skin lipid homeostasis.

Sphingolipids are an essential lipid component of the skin barrier with alterations in skin sphingolipid composition associated with multiple skin disorders including psoriasis, atopic dermatitis, and ichthyosis. Contributions to skin sphingolipid abundance are not well characterized, thus the main method of modulating skin lipid levels is the topical application of creams rich with sphingolipids at the skin surface. Evidence that diet and gut microbiome function can alter skin biology proposes an intriguing potential for the modulation of skin lipid homeostasis through gut microbial metabolism, but potential mechanisms of action are not well understood.

variants among a single host diverge in sphingolipid production.

Sphingolipids serve as vital structural and signaling components of the cell membranes in both eukaryotes and prokaryotes. Within the gut microbiome, species have been identified as major producers of sphingolipids, and -produced sphingolipids have been shown to be modulators of host immune and metabolic functions. While species are a prominent feature of the gut microbiomes of populations living in industrialized countries, , a member of the same phyla, albeit a different family, is the dominant feature across the remainder of the global population, although their sphingolipid-producing capabilities have not been as thoroughly investigated.

Metal transporter SLC39A14/ZIP14 modulates regulation between the gut microbiome and host metabolism.

Metal transporter SLC39A14/ZIP14 is localized on the basolateral side of the intestine, functioning to transport metals from blood to intestine epithelial cells. Deletion of causes spontaneous intestinal permeability with low-grade chronic inflammation, mild hyperinsulinemia, and greater body fat with insulin resistance in adipose. Importantly, antibiotic treatment reverses the adipocyte phenotype of knockout (KO), suggesting a potential gut microbial role in the metabolic alterations in the KO mice.

Characterization of interactions of dietary cholesterol with the murine and human gut microbiome.

Consumption of dietary lipids, such as cholesterol, modulates the gut microbiome with consequences for host health through the production of microbiome-derived metabolites. Despite the implications for host metabolism, a limited number of specific interactions of the gut microbiome with diet-derived lipids have been characterized. This is partially because obtaining species-level resolution of the responsible taxa can be challenging and additional approaches are needed to identify health-relevant metabolites produced from cholesterol-microbiome interactions.

Identification and characterization of 3-ketosphinganine reductase activity encoded at the BT_0972 locus in Bacteroides thetaiotaomicron.

Bacterial sphingolipid synthesis is important for the fitness of gut commensal bacteria with an implied potential for regulating mammalian host physiology. Multiple steps in bacterial sphingolipid synthesis pathways have been characterized previously, with the first step of de novo sphingolipid synthesis being well conserved between bacteria and eukaryotes. In mammals, the subsequent step of de novo sphingolipid synthesis is catalyzed by 3-ketosphinganine reductase, but the protein responsible for this activity in bacteria has remained elusive.

Host hepatic metabolism is modulated by gut microbiota-derived sphingolipids.

Microbially-derived gut metabolites are important contributors to host phenotypes, many of which may link microbiome composition to metabolic disease. However, relatively few metabolites with known bioactivity have been traced from specific microbes to host tissues. Here, we use a labeling strategy to characterize and trace bacterial sphingolipids from the gut symbiont Bacteroides thetaiotaomicron to mouse colons and livers.

A BOSSS method for managing insights into diet-microbiome interactions.

Gut microbial metabolites generated through interactions with dietary constituents are important modulators of host metabolism and physiology. Our understanding of diet-microbiome-host interactions is hampered by the limited tools to broadly identify microbial species that take up nutrients and their products. iorthogonal labeling-ort-equence-pectrometry (BOSSS) overcomes these challenges by leveraging orally introduced alkyne-modified lipids that permit identification of gut microbes that take up dietary lipids.

Dietary sphinganine is selectively assimilated by members of the mammalian gut microbiome.

Functions of the gut microbiome have a growing number of implications for host metabolic health, with diet being one of the most significant influences on microbiome composition. Compelling links between diet and the gut microbiome suggest key roles for various macronutrients, including lipids, yet how individual classes of dietary lipids interact with the microbiome remains largely unknown. Sphingolipids are bioactive components of most foods and are also produced by prominent gut microbes.