FIG 6.

Multi-tiered model of P-gp regulation by butyrate and bile acids. Tier 1: Butyrate and bile acids increase P-gp transcription via HDAC inhibition and nuclear receptor activation (PXR and VDR), respectively. Tier 2: The combination of butyrate and bile acids increases expression of transcription factors that activate, and decrease expression of transcription factors that repress, P-gp transcription resulting in increased P-gp expression. Tier 3: These metabolites increase expression of factors including Pim-1 kinase that contribute to post-translational modifications of P-gp. Diagram created with BioRender.