Physiological concentrations of short-chain fatty acids immediately suppress colonic epithelial permeability
Physiological concentrations of short-chain fatty acids immediately suppress colonic epithelial permeability
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DOI：
10.1017/s0007114508888733
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发表时间：
2008-08-01
影响因子：
3.6
通讯作者：
Hara, Hiroshi
中科院分区：
文献类型：
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作者：
Suzuki, Takuya;Yoshida, Shoko;Hara, Hiroshi
结肠发酵产物SCFA对结肠功能具有多种影响。在这里，我们发现SCFA的生理浓度立即促进大肠上皮屏障功能。将混合和单独SCFA的溶液应用于安装在Ussing型腔室上的盲肠壁。跨上皮电阻（TER）迅速增加，并在应用SCFA混合物（80乙酸盐、40丙酸盐、20丁酸盐（mmol/l））后10分钟内达到比对照样本高35%的峰值。荧光黄的渗透性，细胞旁运输市场，是剂量依赖性降低的混合SCFA，乙酸盐和丙酸盐溶液。单羧酸转运蛋白-1的抑制并不影响醋酸盐的TER增加;然而，降低pH值（从7.5至5.5）明显增强了醋酸盐的作用。SCFA的非代谢、溴代和氯代衍生物也会增加毒性接触率。这些结果表明，SCFA的被动扩散是占主导地位的，SCFA对屏障功能的促进作用不需要SCFA的代谢。我们还观察到单个SCFA剂量依赖性地增加T84和Caco-2细胞中的TER，这表明SCFA直接刺激上皮细胞。膜胆固醇的消耗和磷脂酰肌醇-3激酶和Gq蛋白的抑制剂减弱了醋酸盐介导的促进作用。最后，我们发现粘膜应用SCFA混合物剂量依赖性地抑制了麻醉大鼠中[（3）H]甘露醇从盲肠腔到肠系膜血液的转运。我们的结论是，生理浓度的SCFA立即增强屏障功能的结肠上皮细胞通过富含胆固醇的微区质膜。
Colonic fermentation products, SCFA, have various effects on colonic functions. Here, we found that physiological concentrations of SCFA immediately promote epithelial barrier function in the large intestine. Solutions of mixed and individual SCFA were applied to the caecal walls mounted on Ussing-type chambers. Transepithelial electrical resistance (TER) increased rapidly and reached a peak 35% higher than that in the control specimen within 10 min post application of the SCFA mixture (80 acetate, 40 propionate, 20 butyrate (mmol/l)). The Lucifer yellow permeability, a paracellular transport market, was dose-dependently reduced by the mixed SCFA, acetate and propionate solutions. Inhibition of monocarboxylate transporter-1 did not influence the increase in TER with acetate; however, lowering the pH (from 7.5 to 5.5) clearly enhanced the effect of acetate. Non-metabolizable, bromo and chloro derivatives of SCFA also increased TER. These results suggest that passive diffusion of SCFA is dominant and the metabolism of SCFA is not required for the promotive effect of SCFA on barrier function. We also observed that individual SCFA dose-dependently increased TER in T84 and Caco-2 cells, which indicates that SCFA directly stimulate epithelial cells. Depletion of membrane cholesterol and inhibitors of phosphatidylinositol-3 kinase and Gq protein attenuated the acetate-mediated promotive effect. Finally, we found that the mucosal application of the SCFA mixture dose-dependently Suppressed [(3)H] mannitol transport from the caecal lumen to the mesenteric blood in the anaesthetized rats. We conclude that physiological concentrations of SCFA immediately enhance barrier function of the colonic epithelium through cholesterol-rich microdomain in the plasma membrane.