Gastrointestinal Research Group, Department of Physiology & Pharmacology, Calvin, Phoebe and Joan Snyder Institute of Infection, Inflammation and Immunology, University of Calgary, Calgary, Alberta, Canada.
Inflamm Bowel Dis. 2010 Jul;16(7):1138-48. doi: 10.1002/ibd.21177.
The gut microflora in some patients with Crohn's disease can be reduced in numbers of butyrate-producing bacteria and this could result in metabolic stress in the colonocytes. Thus, we hypothesized that the short-chain fatty acid, butyrate, is important in the maintenance and regulation of the barrier function of the colonic epithelium.
Confluent monolayers of the human colon-derived T84 or HT-29 epithelial cell lines were exposed to dinitrophenol (DNP (0.1 mM), uncouples oxidative phosphorylation) + Escherichia coli (strain HB101, 10(6) cfu) +/- butyrate (3-50 mM). Transepithelial resistance (TER), and bacterial internalization and translocation were assessed over a 24-hour period. Epithelial ultrastructure was assessed by transmission electron microscopy.
Epithelia under metabolic stress display decreased TER and increased numbers of pseudopodia that is consistent with increased internalization and translocation of the E. coli. Butyrate (but not acetate) significantly reduced the bacterial translocation across DNP-treated epithelia but did not ameliorate the drop in TER in the DNP+E. coli exposed monolayers. Inhibition of bacterial transcytosis across metabolically stressed epithelia was associated with reduced I-kappaB phosphorylation and hence NF-kappaB activation.
Reduced butyrate-producing bacteria could result in increased epithelial permeability particularly in the context of concomitant exposure to another stimulus that reduces mitochondria function. We speculate that prebiotics, the substrate for butyrate synthesis, is a valuable prophylaxis in the regulation of epithelial permeability and could be of benefit in preventing relapses in IBD.
一些克罗恩病患者的肠道微生物菌群中丁酸产生菌的数量减少，这可能导致结肠细胞发生代谢应激。因此，我们假设短链脂肪酸丁酸对于维持和调节结肠上皮的屏障功能很重要。
将人结肠衍生的 T84 或 HT-29 上皮细胞系的汇合单层暴露于二硝基苯酚（DNP（0.1mM），解偶联氧化磷酸化）+大肠杆菌（HB101 株，10（6）cfu）+/-丁酸（3-50mM）。在 24 小时内评估跨上皮电阻（TER）以及细菌内化和易位。通过透射电子显微镜评估上皮超微结构。
代谢应激下的上皮显示 TER 降低，伪足数量增加，这与大肠杆菌内化和易位增加一致。丁酸（而非乙酸盐）可显著减少 DNP 处理的上皮中细菌易位，但不能改善 DNP+大肠杆菌暴露单层中 TER 的下降。代谢应激上皮中细菌转胞吞作用的抑制与 I-kappaB 磷酸化减少以及 NF-kappaB 激活有关。
丁酸产生菌减少可能导致上皮通透性增加，特别是在同时暴露于另一种降低线粒体功能的刺激物的情况下。我们推测，丁酸合成的底物益生元对于调节上皮通透性是有价值的预防措施，并可能有助于预防 IBD 的复发。
