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. Sphingolipid synthesis by prominent gut microbes has been shown to affect intestinal, hepatic and immune functions with the potential for sphingolipid-producing bacteria to affect skin biology through altering skin sphingolipid levels. To address this question, we used bioorthogonal chemistry to label lipids from the sphingolipid-producing bacteria Bacteroides thetaiotaomicron and trace these lipids to the skin epidermis. Exposing mice to B. thetaiotaomicron strains mutant in the ability to produce sphingolipids resulted in significantly lower transfer of gut microbiome-derived lipids to the skin, while also altering skin biology and altering expression of skin barrier genes. Measurement of skin ceramide levels, a class of sphingolipids involved in skin barrier function, determined that skin sphingolipid levels were altered in the presence of gut sphingolipid-producing bacteria. Together this work demonstrates that gut bacterial lipids can transfer to the skin and provides a compelling avenue for modulating sphingolipid-dominant compartments of the skin using sphingolipid-producing bacteria of the gut microbiome.