Lipid synthesis is necessary for formation of epithelial barriers and homeostasis with external microbes. An analysis of the response of human keratinocytes to several different commensal bacteria on the skin revealed that Cutibacterium acnes induced a large increase in essential lipids including triglycerides, ceramides, cholesterol, and free fatty acids. A similar response occurred in mouse epidermis and in human skin affected with acne. Further analysis showed that this increase in lipids was mediated by short-chain fatty acids produced by Cutibacterium acnes and was dependent on increased expression of several lipid synthesis genes including glycerol3-phosphate-acyltransferase-3. Inhibition or RNA silencing of peroxisome proliferator–activated receptor–α (PPARα), but not PPARβ and PPARγ, blocked this response. The increase in keratinocyte lipid content improved innate barrier functions including antimicrobial activity, paracellular diffusion, and transepidermal water loss. These results reveal that metabolites from a common commensal bacterium have a previously unappreciated influence on the composition of epidermal lipids.

Normal neonatal human epidermal keratinocytes (NHEKs) were treated with 8mM of propionic acid or with 15% of C. acnes conditioned media or RCM media (control) for 4 days in triplicate. Then, RNA was extracted using the PureLink RNA mini kit. Isolated RNA was submitted to the UCSD IGM Genomics Center for RNA-sequencing performed on a high-output run V4 platform (Illumina, USA) with a single read 100 cycle runs.

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