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

中文翻译：

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与肠道 Na+/H+ 交换受损相关的微生物菌群失调加速并加剧了无菌小鼠的结肠炎。

由顶端 NHE3 (Slc9a3) 促进的肠上皮 Na ⁺ /H ⁺交换是一种受肠道病原体和炎症性肠病抑制的高度调节过程。NHE3 ^-/-小鼠发生自发性细菌介导的结肠炎和 IBD 样生态失调。破坏上皮 Na ⁺ /H ⁺因此，IBD 中的肠道菌群交换可能代表宿主对肠道微生物生态学改变的反应，并且可能在以微生物组依赖的方式调节炎症的严重程度方面发挥关键作用。为了测试在缺乏 NHE3 的环境中培养的微生物组是否能够驱动影响结肠炎发作或严重程度的粘膜免疫反应，我们进行了一系列同居实验，并将粪便微生物组移植到无菌 Rag 缺陷或 IL-10 ^{-/ -}老鼠。我们确定，在 NHE3 缺陷小鼠的微生物组稳定植入受体宿主的环境中，它能够加速实验性结肠炎的发作并加重其严重程度。NHE3 缺陷的特征是 pH 敏感的产丁酸盐厚壁菌门毛螺菌科和瘤胃球菌科（梭状芽孢杆菌 IV 和 XIVa 群）减少，炎症相关类杆菌科细菌增多。我们得出结论，由受损的上皮 Na ⁺ / H ⁺交换培养的微生物组通过破坏肠道微生物生态来增强结肠炎的发作和严重程度。