Penetration of the inner mucus layer in the distal colon by pathogens and/or commensals often found in mice with colitis is related to impaired mucus barrier structure and function caused by genetic deficiency in Muc2100, inactivation of glycosyltransferase-mediated O-glycosylation of Muc2101,102, deficiency of the NLRP6 inflammasome, or exposure to colitis-inducing chemicals103. The gene discussed is NLRP6; the disease is colitis.