Consistent with this idea, MEKK3 activation downstream of Toll-like receptor 4 (TLR4) stimulation by lipopolysaccharide derived from the gut microbiome enhances CCM lesion formation and inhibition of TLR4 signalling or altering the microbiome protects KRIT1 endothelial knockout mice from developing CCM lesions [100]. This evidence concerns the gene MAP3K3 and cerebral cavernous malformation.