第70期：丁酸（处理与否）对肠道CYP活性的影响
原标题：不同来源的丁酸对鸡肠道药物代谢细胞色素P450的营养调节作用
Nutritional modulation of intestinal drug-metabolizing cytochrome P450 by butyrate of different origin in chicken
作者：Anna Kulcsár1* , Gábor Mátis1 , Andor Molnár2 , Janka Petrilla1 , László Wágner2 , Hedvig Fébel3 , Ferenc Husvéth2 , Károly Dublecz2 and Zsuzsanna Neogrády1
1 Department of Physiology and Biochemistry, University of Veterinary Medicine,, István street
2, Budapest, Hungary
2 Department of Animal Sciences and Animal Husbandry, Georgikon Faculty, University of Pannonia, Széchenyi street 11, Keszthely, Hungary
3 Research Institute for Animal Breeding, Nutrition and Meat Science, National Agricultural Research Center, Gesztenyés street 1, Herceghalom, Hungary
来源：Research in Veterinary Science. 2017 Aug;113:25-32.
doi: 10.1016/j.rvsc.2017.07.033.
翻译：肠动力研究院 梁琦
【摘要】肠道细胞色素P450（CYP）酶在口服外源性物质的首过代谢中起关键作用并提供主要代谢屏障，这对维持动物健康和生产特别重要。本文旨在探究营养因子对肉鸡肠道药物代谢CYPs的调节作用。试验研究了不同来源的天然生长促进剂正丁酸(保护或非保护形式的饲料添加剂和/或通过添加高水平的膳食非淀粉性多糖（NSP）来诱导盲肠微生物产生对十二指肠CYPs活性的影响。176羽1日龄的Ross 308肉用仔鸡被随机分成8个处理组，试验准备了两种不同的基础日粮，分别是以玉米为主的基础日粮（MB）和以小麦为主的基础日粮（WB），其中WB日粮中添加了一定量的NSP降解酶。以MB日粮为主的处理组如下，1）CTR组：喂食玉米日粮；2）NP B Lower组：玉米日粮+1.5g/kg未保护的丁酸；3）NP B higher组：玉米日粮+3.0g/kg未保护的丁酸；4）PB组：玉米日粮+0.2g/kg微囊化包被的丁酸。以WB日粮为主的处理组如下，5）CTR组：喂食小麦日粮；6）NP B Lower组：小麦日粮+1.5g/kg未保护的丁酸；7）NP B higher组：小麦日粮+3.0g/kg未保护的丁酸；8）PB组：小麦日粮+0.2g/kg微囊化包被的丁酸。每组22羽，试验为期42天。为了观察肠道CYP活性与丁酸浓度之间的关系，本文还通过测量其在各种肠段和门静脉、体循环的不同血管中的浓度来评估不同来源的丁酸分布。实验结果显示，不同来源的丁酸显示出不同的分布特性，即从胃肠道的不同部分被吸收。日粮添加丁酸和增加盲肠微生物的产丁酸含量可增加肠道中CYP1A和CYP2H2的活性，而CYP3A37的活性受微生物代谢分泌的丁酸的影响最小。研究结果表明，日粮成分和微生物代谢分泌的丁酸均可改变十二指肠上皮细胞CYP的活性。除此外，肠道CYP不仅可以被肠腔内丁酸诱导，也可以通过已吸收的丁酸从基底外侧诱导。丁酸的这一作用从食品安全和药物治疗的角度来看具有特殊的重要性，因为它可能改变外源性物质的代谢和肠道动力学。
【关键词】丁酸，外源性药物，CYP，肉用仔鸡
以下是相关图表
表1：该表计算了各阶段实验日粮的成分和营养成分
表2：不同日粮饲喂的肉鸡平均体重和平均采食量
表3：饲粮类型对肉鸡日增重的影响
图1：饲粮中不同谷物种类和添加丁酸对肉鸡肠道丁酸浓度的影响
A. 十二指肠B.回肠C.回肠
图2：饲粮中不同谷物种类和添加丁酸对肉鸡血浆丁酸浓度的影响
A. 胃十二指肠静脉，B.肠系膜静脉，C.肱静脉
图3：饲粮中不同谷物类型和丁酸对肉鸡肠道CYP活性的影响
A. CYP1A B. CYP2H2 C. CYP3A37
图4：鸡肝门静脉系统到胃肠道的各个分支概述
结论
根据结果来看，相关的营养因子可调节小肠毒物代谢CYP酶的活性，例如，在WB日粮中添加膳食可溶性NSP降解酶，这与盲肠微生物分泌产生丁酸相关，还可通过口服非保护性丁酸。基于作为口服摄入异生素的主要代谢屏障的十二指肠CYP的关键作用，从食品安全的角度来看，改善其功能的所有努力都是值得的。
ABSTRACT
Intestinal cytochrome P450 (CYP) enzymes play key role in the first pass metabolism of orally ingested xenobiotics, providing a primary metabolic barrier, being of special importance in maintaining animal health and production. This study was aimed to investigate how intestinal drug-metabolizing CYPs can be modulated by nutritional factors in broiler chicken. We investigated the effects of the natural growth promoter (n-)butyrate of different origin (feed supplementation of protected or non-protected forms and/or inducing caecal microbial production by supporting higher level of dietary non-starch polysaccharides [NSP]) on the activity of duodenal CYPs. To observe the connection between intestinal CYP activity and butyrate concentration, the distribution of differently originated butyrate was also assessed by measuring its concentration in various intestinal segments and different vessels of portal and systemic circulation. Butyrate of different origin showed varying distribution properties as being absorbed from different parts of the gastrointestinal tract. Intestinal CYP1A and CYP2H2 activities were increased by dietary butyrate supplementation and by the increased caecal microbial butyrate production, while CYP3A37 activity was minimally influenced by microbial butyrate only. The present study proved that both dietary and microbial butyrate could alter the activity of CYPs in the duodenal epithelium. Our findings suggest that intestinal CYPs could be induced not only by the intestinal luminal butyrate, but also from basolateral side, by the already absorbed butyrate. Such action of butyrate can be of special importance from food safety and pharmacotherapeutic point of view as it may modify the metabolism and intestinal kinetics of simultaneously applied xenobiotics.
Conclusion
According to our results, the activity of small intestinal drug-metabolizing CYP enzymes could be modulated by nutrition-associated factors, such as by dietary soluble NSP-degrading enzyme supplementation of WB diet in correlation with caecal microbial butyrate production, and by oral non-protected butyrate application. Based on the key role of duodenal CYPs as a primary metabolic barrier against orally ingested xenobiotics, all efforts altering their function could be of high importance from food safety point of view.
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