The TLR4 activation, the receptor for LPS generated by the gut microbiome in the epithelial cells, can induce tumor development by up-regulating prostaglandin-endoperoxide synthase 2 (PTGS2) and activating the epidermal growth factor receptor (EGFR) signaling pathway in mice receiving AOM (Fig. 1C) [55]. Here, EGFR is linked to infectious otitis media.