Division of Biological Sciences, Department of Medicine, The University of Chicago, 900 E. 57th St., Chicago, IL 60637, USA.
Dig Dis Sci. 2013 Mar;58(3):668-77. doi: 10.1007/s10620-012-2509-5. Epub 2013 Jan 18.
Lubiprostone has been used to treat constipation through its effects to stimulate Cl(-) secretion, resulting in water and electrolyte secretion.
Potential associated changes in intestinal mucus and the colonizing bacteria (microbiome) have not been studied. As mucus obstructions may play a role in cystic fibrosis, the hypothesis that lubiprostone alters intestinal mucus and the microbiome was investigated.
Ion transport studies were performed ex vivo. For mucus and microbiome studies, mice were gavaged daily with lubiprostone or vehicle. Mucin from intestinal sections was analyzed in Carnoy's fixed tissues stained with Alcian blue. Microbiome composition was analyzed by 16S rRNA gene-based sequencing.
Lubiprostone stimulated short circuit current in all mouse intestinal segments after both serosal and mucosal additions, albeit at lower concentrations in the latter. Current was Cl-dependent and blocked by mucosal diphenylcarboxylic acid, serosal bumetanide, and serosal Ba(++). The CFTR inhibitor CFTRinh172 had a marginal effect. Mucus near epithelial cells (inner layer mucus) was not present in the small intestine of any mice. Proximal colon inner mucus layer was thicker in ∆F/∆F compared with +/∆F and +/+ mice. Lubiprostone decreased inner mucus layer thickness in both proximal and distal colon of all mice. Furthermore, lubiprostone altered the intestinal microbiome by increasing abundance of Lactobacillus and Alistipes.
Lubiprostone activates non-CFTR Cl(-) secretion and alters the colonic inner mucus layer, which is associated with changes in the composition of the enteric microbiome.
鲁比前列酮通过刺激 Cl(-)分泌来治疗便秘，从而导致水和电解质分泌。
尚未研究肠道黏液和定植细菌（微生物组）的潜在相关变化。由于黏液阻塞可能在囊性纤维化中起作用，因此研究了鲁比前列酮改变肠道黏液和微生物组的假设。
在离体条件下进行离子转运研究。对于黏液和微生物组研究，每天用鲁比前列酮或载体灌胃小鼠。用 Alcian 蓝染色的 Carnoy 固定组织分析肠段中的粘蛋白。通过基于 16S rRNA 基因的测序分析微生物组组成。
鲁比前列酮在所有小鼠肠道段的浆膜和黏膜后均刺激短路电流，尽管后者的浓度较低。电流是 Cl(-)依赖性的，并被黏膜二苯甲酮酸、浆膜布美他尼和浆膜 Ba(++) 阻断。CFTR 抑制剂 CFTRinh172 仅有轻微作用。没有任何小鼠的小肠上皮细胞附近存在黏液（内层黏液）。与+/∆F 和 +/+ 小鼠相比，∆F/∆F 小鼠的近端结肠内层黏液层更厚。鲁比前列酮减少了所有小鼠近端和远端结肠的内层黏液层厚度。此外，鲁比前列酮通过增加乳杆菌和 Alistipes 的丰度改变了肠道微生物组。
鲁比前列酮激活非 CFTR Cl(-)分泌并改变结肠内层黏液层，这与肠内微生物组组成的变化有关。
