Microbial dysbiosis associated with impaired intestinal Na+/H+ exchange accelerates and exacerbates colitis in ex-germ free mice.

摘要: Intestinal epithelial Na+/H+ exchange facilitated by the apical NHE3 (Slc9a3) is a highly regulated process inhibited intestinal pathogens and in inflammatory bowel diseases. NHE3-/- mice develop spontaneous, bacterially mediated colitis, IBD-like dysbiosis. Disruption of IBD may thus represent host response contributing to altered gut microbial ecology, play pivotal role modulating severity inflammation microbiome-dependent manner. To test whether microbiome fostered an NHE3-deficient environment able drive mucosal immune responses affecting onset or we performed series cohousing experiments fecal transplants into germ-free Rag-deficient IL-10-/- mice. We determined that settings where was stably engrafted recipient host, it accelerate amplify experimental colitis. NHE3-deficiency characterized reduction pH-sensitive butyrate-producing Firmicutes families Lachnospiraceae Ruminococcaceae (Clostridia clusters IV XIVa), with expansion inflammation-associated Bacteroidaceae. conclude impaired enhances colitis through disruption ecology.