Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, K.U. Leuven, Leuven, Belgium.
Inflamm Bowel Dis. 2012 Jun;18(6):1127-36. doi: 10.1002/ibd.21894. Epub 2011 Oct 10.
In ulcerative colitis (UC) butyrate metabolism is impaired due to a defect in the butyrate oxidation pathway and/or transport. In the present study we correlated butyrate uptake and oxidation to the gene expression of the butyrate transporter SLC16A1 and the enzymes involved in butyrate oxidation (ACSM3, ACADS, ECHS1, HSD17B10, and ACAT2) in UC and controls.
Colonic mucosal biopsies were collected during endoscopy of 88 UC patients and 20 controls with normal colonoscopy. Butyrate uptake and oxidation was measured by incubating biopsies with (14) C-labeled Na-butyrate. To assess gene expression, total RNA from biopsies was used for quantitative reverse-transcription polymerase chain reaction (qRT-PCR). In 20 UC patients, gene expression was reassessed after treatment with infliximab.
Butyrate uptake and oxidation were significantly decreased in UC versus controls (P < 0.001 for both). Butyrate oxidation remained significantly reduced in UC after correction for butyrate uptake (P < 0.001), suggesting that the butyrate oxidation pathway itself is also affected. Also, the mucosal gene expression of SLC16A1, ACSM3, ACADS, ECHS1, HSD17B10, and ACAT2 was significantly decreased in UC as compared with controls (P < 0.001 for all). In a subgroup of patients (n = 20), the gene expression was reassessed after infliximab therapy. In responders to therapy, a significant increase in gene expression was observed. Nevertheless, only ACSM3 mRNA levels returned to control values after therapy in the responders groups.
The deficiency in the colonic butyrate metabolism in UC is initiated at the gene expression level and is the result of a decreased expression of SLC16A1 and enzymes in the β-oxidation pathway of butyrate.
在溃疡性结肠炎（UC）中，由于丁酸盐氧化途径和/或转运的缺陷，丁酸盐代谢受损。在本研究中，我们将丁酸盐摄取和氧化与丁酸盐转运体 SLC16A1 的基因表达以及 UC 和对照组中涉及丁酸盐氧化的酶（ACSM3、ACADS、ECHS1、HSD17B10 和 ACAT2）相关联。
在 88 例 UC 患者和 20 例结肠镜正常的对照者行内镜检查期间，收集结肠黏膜活检。通过孵育活检与（14）C 标记的 Na-丁酸盐来测量丁酸盐摄取和氧化。为了评估基因表达，使用活检的总 RNA 进行定量逆转录聚合酶链反应（qRT-PCR）。在 20 例 UC 患者中，在用英夫利昔单抗治疗后重新评估基因表达。
与对照组相比，UC 中的丁酸盐摄取和氧化明显降低（两者均 P < 0.001）。在校正丁酸盐摄取后，UC 中的丁酸盐氧化仍明显降低（P < 0.001），这表明丁酸盐氧化途径本身也受到影响。此外，与对照组相比，UC 中的 SLC16A1、ACSM3、ACADS、ECHS1、HSD17B10 和 ACAT2 的黏膜基因表达也明显降低（所有 P < 0.001）。在患者的亚组（n = 20）中，在英夫利昔单抗治疗后重新评估了基因表达。在对治疗有反应的患者中，观察到基因表达的显著增加。然而，只有在治疗后，在有反应的患者组中，ACSM3 mRNA 水平才恢复到对照值。
UC 中结肠丁酸盐代谢的缺陷始于基因表达水平，是 SLC16A1 和丁酸盐β-氧化途径中酶表达降低的结果。
Zotero 插件