The Short-Chain Fatty Acid Sodium Butyrate Functions as a Regulator of the Skin Immune System

There is evidence that gut commensal microbes affect the mucosal immune system via expansion of regulatory T cells (Tregs) in the colon. This is mediated via short-chain fatty acids, bacterial metabolites generated during fiber fermentation, which include butyrate, propionate, and acetate. We postulated that short-chain fatty acids produced by commensal skin bacteria may also activate resident skin Tregs, the activity of which is diminished in certain inflammatory dermatoses. Sodium butyrate (SB) either injected subcutaneously or applied topically onto the ears of hapten-sensitized mice significantly reduced the contact hypersensitivity reaction. This effect was histone acetylation-dependent because suppression was abrogated by anacardic acid, a histone acetyltransferase inhibitor. The genes encoding for the Treg-specific transcription factor foxp3 and for IL-10 were up-regulated upon treatment with sodium butyrate, as determined by quantitative real-time reverse transcription-PCR. Immunofluorescence analysis showed enhanced numbers of Foxp3-positive cells in sodium butyrate-treated skin. Additionally, CD4(+)CD25 e nonregulatory human T cells exerted suppressive features upon incubation with sodium butyrate. This indicates that Tregs can be induced by short-chain fatty acids, suggesting (i) that resident skin microbes may prevent exaggerated inflammatory responses by exerting a down-regulatory function and thereby maintaining a stable state under physiologic conditions and (ii) that short-chain fatty acids may be used therapeutically to mitigate inflammatory skin reactions.