直肠给药丁酸盐的肝脏摄取可防止人体全身丁酸盐浓度升高。

Hepatic Uptake of Rectally Administered Butyrate Prevents an Increase in Systemic Butyrate Concentrations in Humans.

作者信息

van der Beek Christina M, Bloemen Johanne G, van den Broek Maartje A, Lenaerts Kaatje, Venema Koen, Buurman Wim A, Dejong Cornelis H

机构信息

Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands; Top Institute Food & Nutrition, Wageningen, Netherlands; and

Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands; Top Institute Food & Nutrition, Wageningen, Netherlands; and.

出版信息

J Nutr. 2015 Sep;145(9):2019-24. doi: 10.3945/jn.115.211193. Epub 2015 Jul 8.

Abstract

BACKGROUND

Short-chain fatty acids (SCFAs), fermentation products of undigested fibers, are considered beneficial for colonic health. High plasma concentrations are potentially harmful; therefore, information about systemic SCFA clearance is needed before therapeutic use of prebiotics or colonic SCFA administration.

OBJECTIVE

The aim of this study was to investigate the effect of rectal butyrate administration on SCFA interorgan exchange.

METHODS

Twelve patients (7 men; age: 66.4 ± 2.0 y; BMI 24.5 ± 1.4 kg/m(2)) undergoing upper abdominal surgery participated in this randomized placebo-controlled trial. During surgery, 1 group received a butyrate enema (100 mmol sodium butyrate/L; 60 mL; n = 7), and the other group a placebo (140 mmol 0.9% NaCl/L; 60 mL; n = 5). Before and 5, 15, and 30 min after administration, blood samples were taken from the radial artery, hepatic vein, and portal vein. Plasma SCFA concentrations were analyzed, and fluxes from portal-drained viscera, liver, and splanchnic area were calculated and used for the calculation of the incremental area under the curve (iAUC) over a 30-min period.

RESULTS

Rectal butyrate administration led to higher portal butyrate concentrations at 5 min compared with placebo (92.2 ± 27.0 μmol/L vs. 14.3 ± 3.4 μmol/L, respectively; P < 0.01). In the butyrate-treated group, iAUCs of gut release (282.8 ± 133.8 μmol/kg BW · 0.5 h) and liver uptake (-293.7 ± 136.0 μmol/kg BW · 0.5 h) of butyrate were greater than in the placebo group [-16.6 ± 13.4 μmol/kg BW · 0.5 h (gut release) and 16.0 ± 13.8 μmol/kg BW · 0.5 h (liver uptake); P = 0.01 and P < 0.05, respectively]. As a result, splanchnic butyrate release did not differ between groups.

CONCLUSION

After colonic butyrate administration, splanchnic butyrate release was prevented in patients undergoing upper abdominal surgery. These observations imply that therapeutic colonic SCFA administration at this dose is safe. The trial was registered at clinicaltrials.gov as NCT02271802.

摘要

背景

短链脂肪酸(SCFAs)是未消化纤维的发酵产物,被认为对结肠健康有益。血浆高浓度可能有害;因此,在益生元治疗应用或结肠给予SCFAs之前,需要有关全身SCFAs清除的信息。

目的

本研究旨在调查直肠给予丁酸盐对SCFAs器官间交换的影响。

方法

12例接受上腹部手术的患者(7例男性;年龄:66.4±2.0岁;体重指数24.5±1.4kg/m²)参与了这项随机安慰剂对照试验。手术期间,一组接受丁酸盐灌肠(100mmol丁酸钠/L;60mL;n=7),另一组接受安慰剂(140mmol0.9%氯化钠/L;60mL;n=5)。在给药前以及给药后5、15和30分钟,从桡动脉、肝静脉和门静脉采集血样。分析血浆SCFAs浓度,并计算门静脉引流内脏、肝脏和内脏区域的通量,用于计算30分钟内的曲线下增量面积(iAUC)。

结果

与安慰剂相比,直肠给予丁酸盐在5分钟时导致门静脉丁酸盐浓度更高(分别为92.2±27.0μmol/L和14.3±3.4μmol/L;P<0.01)。在丁酸盐治疗组中,丁酸盐的肠道释放iAUC(282.8±133.8μmol/kg体重·0.5小时)和肝脏摄取iAUC(-293.7±136.0μmol/kg体重·0.5小时)大于安慰剂组[-16.6±13.4μmol/kg体重·0.5小时(肠道释放)和16.0±13.8μmol/kg体重·0.5小时(肝脏摄取);P分别为0.01和P<0.05]。结果,两组之间的内脏丁酸盐释放没有差异。

结论

结肠给予丁酸盐后,上腹部手术患者的内脏丁酸盐释放得到抑制。这些观察结果表明,以该剂量进行治疗性结肠给予SCFAs是安全的。该试验已在clinicaltrials.gov上注册,注册号为NCT02271802。

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