Fig. 6

A working model of microbiome-driven P-gp expression. We have identified a bacterial population containing Bacilli and Clostridia classes that is sufficient to induce P-gp expression in the colon. Butyrate and secondary bile acids produced by these bacteria from dietary substrates together potentiate the induction of functional P-gp expression on the epithelium which is capable of blocking neutrophil migration through efflux of its endogenous substrates, endocannabinoids [2]. Our observations suggest converging intracellular pathways to amplify P-gp expression; we propose these pathways include one or more of the following: GPCR activation, HDAC inhibition, NRF2 activation, PXR activation. Schematic made with BioRender