HRH2 and colitis: histamine H2 receptor (H2R) to elevate cAMP levels and inhibit the downstream MEK/ERK MAPK signaling, which inhibits the TLR-induced TNF-α production.161 Histamine-induced H2R activation plays a critical role in Lactobacillus reuteri-driven suppression of intestinal inflammation.162 Another study found microbiota-associated histamine as well as spermine reduced NLRP6 inflammasome assembly and decreased IL-18 secretion to regulate the host immune homeostasis and affect the host susceptibility to colitis.163