动物营养学报    2020, Vol. 32 Issue (5): 1973-1979    PDF    
丁酸对断奶仔猪腹泻的缓解作用及其机理研究进展
胡宁敏1 , 陈代文1 , 余冰1 , 赵叶1,2     
1. 四川农业大学动物营养研究所, 教育部动物抗病营养重点实验室, 成都 611130;
2. 四川农业大学动物科技学院, 成都 611130
摘要: 丁酸是一种短链脂肪酸,主要由饲粮中不可消化碳水化合物经肠道产丁酸菌酵解产生。丁酸能通过增强肠道上皮屏障功能、优化肠道菌群和降低肠道炎症反应等途径缓解断奶仔猪腹泻。本文就丁酸对断奶仔猪腹泻的缓解作用及其机理作一简要综述。
关键词: 丁酸    断奶仔猪    腹泻    肠道上皮屏障    肠道菌群    炎症    
Research Progress on Relaxation Effects of Butyric Acid on Diarrhea in Weaned Piglets and Its Mechanism
HU Ningmin1 , CHEN Daiwen1 , YU Bing1 , ZHAO Ye1,2     
1. Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China;
2. College of Animal Science, Sichuan Agricultural University, Chengdu 611130, China
Abstract: Butyric acid is a short-chain fatty acid, which is mainly produced by digestible carbohydrates in diets fermented by intestinal butyric acid-producing bacteria. Butyric acid could relieve diarrhea in weaned piglets by enhancing intestinal epithelial barrier function, optimizing intestinal flora, and reducing intestinal inflammatory reaction. The relaxation effect of butyric acid on diarrhea in weanled piglets and its mechanism were reviewed in this paper.
Key words: butyric acid    weaned piglets    diarrhea    intestinal epithelial barrier    intestinal flora    inflammation    

断奶后仔猪腹泻发生率很高,病愈后的仔猪往往生长发育不良,日增重明显下降,因而造成较大的经济损失[1]。抗生素可以提高动物的生长速度和饲料利用率,并减少动物腹泻的发生率[2]。但抗生素的广泛使用会导致病原菌产生耐药性,使病原菌抵抗抗生素的能力增强,严重威胁人和动物的健康。因此,我国农业农村部颁发相关条例,自2015年12月31日起禁止在畜禽的饮食中添加洛美沙星、培氟沙星、氧氟沙星和诺氟沙星等4种抗生素。2019年7月,农业农村部发布公告,明确规定自2020年7月1日起,饲料企业停止生产含促生长类药物饲料添加剂(中草药除外)的商品饲料。在全面禁抗的时代背景下,寻找和科学使用抗生素替代品能降低“饲料禁抗”对于养殖行业的不利影响,而丁酸及其盐类(如丁酸钠,丁酸盐是丁酸的承载体,真正起作用的是丁酸)作为抗生素替代品,受到了研究者的广泛关注[3]。近年来的研究表明,仔猪断奶后,在饲粮中添加丁酸及其盐类能够有效缓解仔猪的腹泻[4-6]。本文就丁酸对断奶仔猪腹泻的缓解作用及其机理研究进展作一简要综述。

1 丁酸能缓解断奶仔猪腹泻

腹泻率和腹泻指数是评定动物腹泻情况的指标,腹泻率越大,腹泻指数越高,表示动物腹泻越严重。Huang等[4]研究发现,在28日龄断奶仔猪饲粮中添加1 g/kg丁酸钠并饲喂28 d后,其腹泻率为11.3%,较对照组显著降低33.50%。Feng等[5]的研究结果表明,给21日龄断奶仔猪饲喂含2 g/kg丁酸钠的饲粮21 d后,仔猪腹泻率和腹泻指数分别较对照组显著降低85.78%和59.89%。Fang等[6]发现,给28日龄断奶仔猪饲喂含1 g/kg丁酸钠的饲粮21 d后,仔猪腹泻率较对照组显著降低28.32%。另外,在生长肥育猪上也有相同的结果,不管是在37~70 kg、71~98 kg阶段,还是在37~98 kg的整个饲养阶段,基础饲粮中添加1 g/kg丁酸钠均能显著降低腹泻率,分别较对照组降低70%、100%和77%[7]。以上试验结果表明饲粮中添加适宜水平的丁酸钠能有效缓解断奶仔猪腹泻。然而,在不同试验条件下,添加不同水平丁酸钠缓解断奶仔猪腹泻的程度有所不同,这可能与仔猪断奶天数、饲粮中丁酸钠添加水平以及饲喂时间有关。由表 1可知,仔猪断奶越早,体重越小,可能需要添加的丁酸钠量越高;丁酸钠饲喂时间越长,降低腹泻的效果可能越好。

表 1 丁酸钠对断奶仔猪腹泻的影响 Table 1 Effects of sodium butyrate on diarrhea of weaned piglets
2 丁酸缓解断奶仔猪腹泻的机理 2.1 丁酸通过减轻炎症反应来缓解腹泻

仔猪断奶后,营养和环境等应激使得仔猪肠道形态和功能发生改变,肠腔内有害物质进入肠道黏膜下层,引发异常的肠道免疫反应,造成肠道免疫系统紊乱,导致严重的肠道炎症反应[8-10]。通常炎症反应过程中伴随着细胞因子表达量的变化,其中的促炎细胞因子包括肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、白细胞介素-8(interleukin-8,IL-8)、白细胞介素-18(interleukin-18,IL-18)和干扰素-γ(interferon-γ,IFN-γ),抗炎细胞因子包括白细胞介素-10(interleukin-10,IL-10)和转化生长因子-β(transforming growth factor-β,TGF-β)。研究表明,断奶导致仔猪肠道组织中TNF-α、IL-6、IL-8和IFN-γ等促炎细胞因子的表达量升高,TGF-β等抗炎细胞因子的表达量降低,引发肠道炎症反应[11-13]。Jacob等[14]研究证实,在应激状态下,肥大细胞通过脱颗粒释放细胞因子和多种炎性递质来影响肠黏膜屏障功能,而TNF-α可诱导肠上皮细胞间紧密连接蛋白分解和功能改变,从而导致肠上皮通透性增加,损伤肠黏膜机械屏障功能。研究发现,丁酸钠显著降低了断奶仔猪回肠中TNF-αIFN-γ的表达[4];此外,丁酸钠显著下调了新生仔猪回肠中IL-6、IL-8、IL-18和IFN-γ mRNA的表达量,上调了IL-10和TGF-β mRNA的表达量[15];丁酸钠对仔猪肠道炎症反应相关因子的影响具体见表 2。以上结果说明丁酸能通过降低促炎细胞因子的表达和增加抗炎细胞因子的表达来减轻炎症反应,进而缓解断奶导致的仔猪腹泻。

表 2 丁酸钠对仔猪肠道炎症反应相关因子的影响 Table 2 Effects of sodium butyrate on intestinal inflammatory response-related factors of piglets

丁酸能通过调控多种炎症相关通路的活性,调节炎性细胞因子的释放,抑制肠道炎症反应,其中丁酸能调节核转录因子-κB(nuclear factor-kappa B,NF-κB)信号通路。NF-κB信号通路是炎症反应的经典通路,当机体受到刺激时,NF-κB抑制蛋白(IκB)激酶(IKK)被激活,导致IκB的磷酸化和泛素化,进而NF-κB被激活和向细胞核内迁移,激活NF-κB信号通路下游炎症因子的表达[16]。研究表明,仔猪断奶会促进IκB的磷酸化,进而提高NF-κB磷酸化水平,促进下游促炎细胞因子大量转录,引发肠道炎症反应[13, 17]。Aguilar等[18]研究发现,丁酸钠可以增加细胞浆中p50的浓度,降低p65的浓度并抑制其向细胞核中转移,导致抑制性p50/p50同源二聚体的量增加,从而抑制NF-κB信号通路的活性。此外,丁酸钠还可以通过抑制IκB的磷酸化来抑制NF-κB信号通路的活性[19]。因此,丁酸可以通过抑制NF-κB信号通路的活性降低促炎细胞因子的转录,抑制炎症反应的发生,从而缓解仔猪断奶腹泻。

2.2 丁酸通过增强肠道黏膜机械屏障功能来缓解腹泻

肠黏膜机械屏障是由肠道黏膜上皮细胞、细胞间紧密连接和黏液层构成,是指正常机械屏障的黏膜上皮细胞及其细胞间的各种连接结构,它不仅是肠道抵御有害物质入侵肠黏膜组织的关键,也是维持肠上皮的选择通透性及其屏障功能的结构基础。其中,细胞间紧密连接调节着各种物质的跨细胞旁路的被动转运,当其功能受损时,肠道通透性增加,引起肠黏膜机械屏障损伤,导致胃肠功能紊乱[20]。乳果糖通过小肠黏膜上皮细胞间的紧密连接被吸收,而甘露醇通过细胞膜途径吸收,两者在体内不进行代谢,从肠道入血后由尿中排出。当细胞间紧密连接受损时,乳果糖从肠道吸收增加,而甘露醇吸收变化不大,尿液中乳果糖和甘露醇的比值增加,反映肠道通透性增加,肠道黏膜机械屏障受损[21]。Feng等[5]给21日龄断奶仔猪饲喂含2 g/kg丁酸钠的饲粮,利用高效液相色谱法检测饲喂7、14和21 d后尿中乳果糖和甘露醇的含量,结果显示丁酸钠组3个时间段尿中乳果糖和甘露醇的比值均显著低于对照组。Huang等[4]发现,用含1 g/kg丁酸钠的饲粮饲喂21日龄断奶仔猪28 d时,尿液中乳果糖和甘露醇的比值显著低于对照组,而与吉他霉素和黏菌素抗生素组则没有显著差异。丁酸钠对断奶仔猪肠道屏障功能的影响具体见表 3。这些结果表明丁酸能降低肠道通透性,修复肠道黏膜机械屏障。

表 3 丁酸钠对断奶仔猪肠道屏障功能的影响 Table 3 Effects of sodium butyrate on intestinal barrier function of weaned piglets

紧密连接复合体主要由跨膜蛋白和细胞溶质支架蛋白构成,其中跨膜蛋白主要包括闭锁蛋白(occludin)和闭合蛋白(claudin),细胞溶质支架蛋白包括闭锁小带蛋白(zonula occludens,ZO)。紧密连接复合体相关分子基因和蛋白表达下降,会引起紧密连接结构和功能的改变,进而损害肠道黏膜机械屏障功能[22]。Huang等[4]发现,饲粮中添加丁酸钠能增加断奶仔猪空肠和结肠occludin的mRNA表达量。Feng等[5]的研究结果显示,丁酸钠可增加断奶仔猪回肠中claudin-3和occludin的mRNA表达量,结肠中ZO-1、claudin-3和occludin mRNA的表达量以及claudin-3和occludin蛋白的表达量。与此同时,利用免疫荧光试验结果也证明了丁酸钠能有效增加断奶仔猪结肠组织中claudin-3蛋白的表达量[5]。Yan等[23]的在体外试验中发现,培养基中添加0.1和1.0 mmol/L的丁酸钠预处理猪小肠上皮细胞-J2(IPEC-J2)细胞系7 d,能显著增加claudin-3和claudin-4的mRNA和蛋白表达量,而且对脂多糖(LPS)诱导的claudin-3和claudin-4 mRNA和蛋白表达量的下调具有减轻作用。丁酸钠对断奶仔猪肠道紧密连接蛋白mRNA表达的影响详见表 4。这些结果说明丁酸钠可以提高肠道组织中紧密连接蛋白的表达量,增强肠上皮细胞间屏障功能,维持肠黏膜完整性,从而降低断奶仔猪腹泻的发生。

表 4 丁酸钠对断奶仔猪肠道紧密连接蛋白mRNA表达的影响 Table 4 Effects of sodium butyrate on mRNA expression of tight junction proteins in intestine of weaned piglets

研究表明,丁酸能增强肠道上皮细胞的增殖和分化,并减少正常上皮细胞的凋亡,改善肠道形态,提高肠道屏障功能[24-25]。罗海祥[24]研究发现,饲粮中添加1 g/kg丁酸钠可显著降低21日龄断奶仔猪十二指肠的隐窝深度,同时绒毛高度和隐窝深度的比值较对照组提高57.79%。王继凤等[25]在饲粮中添加1 g/kg丁酸钠后,断奶仔猪空肠和结肠的黏膜上皮更加完整,肠绒毛更为粗壮,其中杯状细胞数量比抗生素组多1.55倍。以上结果说明丁酸可维持肠道黏膜上皮细胞结构完整性,增强肠黏膜机械屏障功能,进而降低断奶仔猪腹泻。但有关丁酸对肠道黏液层影响的研究较少,有待进一步研究。

2.3 丁酸通过改善肠道菌群结构来缓解腹泻

肠道菌群是宿主生理和健康状况的一个重要决定因素,在维持肠道正常生理功能方面起着关键作用[26-28]。正常情况下,肠道菌群处于动态平衡中。当宿主肠道受到不良应激时,肠道细菌种群数越多、分配的均匀度越高,菌群之间的相互依赖和制约能力就越强,菌群就能更好地维持动态平衡和拥有更佳的缓冲能力,从而加强宿主应对应激等不良环境因素的抵抗能力[29]。Chao指数可反映肠道菌群的物种丰度,Shannon指数可反映肠道菌群的多样性,Simpson指数可反映肠道菌群中优势种的集中程度,Chao指数和Shannon指数越大,Simpson指数越小,说明肠道菌群越丰富多样[30]。Xu等[15]发现,丁酸钠组新生仔猪结肠Chao指数和Shannon指数显著高于对照组,Simpson指数显著低于照组。Huang等[4]发现,丁酸钠组断奶仔猪结肠中Shannon指数较对照组升高23.41%,Simpson指数较对照组降低37.5%。这些结果表明丁酸能通过改善断奶仔猪肠道菌群物种多样性,加强仔猪应对断奶应激的能力,从而缓解腹泻。

仔猪断奶后,其正常的肠道菌群平衡被打破,乳杆菌等有益菌的生存条件受到限制,同时大肠杆菌等有害菌大量增殖而引起腹泻[31]。断奶仔猪肠道内的有益菌主要有乳杆菌、双歧杆菌、梭菌和放线菌等,有害菌主要有大肠杆菌、沙门氏菌和变形菌等[32-34]。李虹瑾等[35]在基础饲粮中添加包膜丁酸钠后发现,断奶仔猪盲肠和结肠中乳杆菌和双歧杆菌的数量显著增加,回肠中大肠杆菌的数量显著降低。Huang等[4]发现丁酸钠组断奶仔猪回肠腔中梭菌科的丰度为83.2%,显著高于对照组的0.3%,结肠腔中也观察到梭菌科的丰度较对照组显著增加;此外,丁酸钠组断奶仔猪回肠腔中大肠杆菌的丰度相比于对照组有所减少。Immerseel等[36]发现丁酸可显著降低肉仔鸡沙门氏菌感染后盲肠中沙门氏菌定植数量。研究发现,未解离形式的丁酸可以穿透细菌的细胞膜,分解成丁酸根离子和氢离子,随着胞内氢离子浓度的提升,对氢离子耐受性差的有害菌大量消亡,而抗酸性的乳酸菌等有益菌得以存活[35, 37-38]。因此,丁酸能通过增加肠道有益菌的数量和降低有害菌的数量,改善肠道菌群使其处于正平衡进而缓解断奶腹泻。

3 小结

丁酸是重要的细菌代谢产物,对维持肠道健康有着至关重要的作用[39]。丁酸能缓解断奶仔猪腹泻,其主要通过:1)提高肠道紧密连接蛋白的表达量,增强肠上皮细胞间屏障功能,降低断奶仔猪腹泻;2)改善断奶仔猪肠道菌群物种多样性,加强仔猪应对断奶应激的能力,从而缓解腹泻;3)抑制NF-κB通路的活性来降低促炎细胞因子的转录,抑制炎症反应的发生,缓解仔猪断奶腹泻。仔猪断奶过程中,当肠道的屏障功能受到应激而遭受损伤时,添加丁酸能降低肠道通透性,减少有害物质进入机体,调节肠道菌群,缓解炎症反应,进而增强肠道屏障功能,降低腹泻发病率。综上所述,丁酸可以通过多重机理来降低仔猪断奶腹泻率,对于仔猪早期断奶应激引起的腹泻的治疗有着重要意义。

参考文献
[1]
VAN NIEUWAMERONGEN S E, BOLHUIS J E, VAN DER PEET-SCHWERING C M C, et al. Effects of pre-weaning housing in a multi-suckling system on performance and carbohydrate absorption of relatively light and heavy piglets around weaning[J]. Animal, 2018, 12(4): 802-809.
[2]
PARTANEN K H, MROZ Z. Organic acids for performance enhancement in pig diets[J]. Nutrition Research Reviews, 1999, 12(1): 117-145.
[3]
THACKER P A. Alternatives to antibiotics as growth promoters for use in swine production:a review[J]. Journal of Animal Science and Biotechnology, 2013, 4(1): 35. DOI:10.1186/2049-1891-4-35
[4]
HUANG C, SONG P X, FAN P X, et al. Dietary sodium butyrate decreases postweaning diarrhea by modulating intestinal permeability and changing the bacterial communities in weaned piglets[J]. The Journal of Nutrition, 2015, 145(12): 2774-2780. DOI:10.3945/jn.115.217406
[5]
FENG W, WU Y, CHEN G, et al. Sodium butyrate attenuates diarrhea in weaned piglets and promotes tight junction protein expression in colon in a GPR109A-dependent manner[J]. Cellular Physiology and Biochemistry, 2018, 47(4): 1617-1629. DOI:10.1159/000490981
[6]
FANG C L, SUN H, WU J, et al. Effects of sodium butyrate on growth performance, haematological and immunological characteristics of weanling piglets[J]. Journal of Animal Physiology and Animal Nutrition, 2014, 98(4): 680-685. DOI:10.1111/jpn.12122
[7]
唐明红, 王启军, 胡麟, 等. 丁酸钠对生长肥育猪生产性能影响的研究[J]. 饲料工业, 2010, 31(6): 6-9. DOI:10.3969/j.issn.1001-991X.2010.06.002
[8]
LALLÈS J P, BOSI P, SMIDT H, et al. Weaning-a challenge to gut physiologists[J]. Livestock Science, 2007, 108(1/2/3): 82-93.
[9]
HEO J M, OPAPEJU F O, PLUSKE J R, et al. Gastrointestinal health and function in weaned pigs:a review of feeding strategies to control post-weaning diarrhoea without using in-feed antimicrobial compounds[J]. Journal of Animal Physiology and Animal Nutrition, 2013, 97(2): 207-237. DOI:10.1111/j.1439-0396.2012.01284.x
[10]
易宏波.抗菌肽CWA对断奶仔猪肠道炎症和肠道屏障功能的作用及其机制[D].博士学位论文.杭州: 浙江大学, 2016. http://cdmd.cnki.com.cn/Article/CDMD-10335-1016267417.htm
[11]
PIÉ S, LALLÈS J P, BLAZY F, et al. Weaning is associated with an upregulation of expression of inflammatory cytokines in the intestine of piglets[J]. The Journal of Nutrition, 2004, 134(3): 641-647. DOI:10.1093/jn/134.3.641
[12]
MEI J, XU R J. Transient changes of transforming growth factor-β expression in the small intestine of the pig in association with weaning[J]. British Journal of Nutrition, 2005, 93(1): 37-45. DOI:10.1079/BJN20041302
[13]
YI H B, JIANG D H, ZHANG L, et al. Developmental expression of STATs, nuclear factor-κB and inflammatory genes in the jejunum of piglets during weaning[J]. International Immunopharmacology, 2016, 36: 199-204. DOI:10.1016/j.intimp.2016.04.032
[14]
JACOB C, YANG P C, DARMOUL D, et al. Mast cell tryptase controls paracellular permeability of the intestine.Role of protease-activated receptor 2 and β-arrestins[J]. The Journal of Biological Chemistry, 2005, 280(36): 31936-31948. DOI:10.1074/jbc.M506338200
[15]
XU J M, CHEN X, YU S Q, et al. Effects of early intervention with sodium butyrate on gut microbiota and the expression of inflammatory cytokines in neonatal piglets[J]. PLoS One, 2016, 11(9): e0162461. DOI:10.1371/journal.pone.0162461
[16]
WULLAERT A, BONNET M C, PASPARAKIS M. NF-κB in the regulation of epithelial homeostasis and inflammation[J]. Cell Research, 2011, 21(1): 146-158. DOI:10.1038/cr.2010.175
[17]
MOESER A J, KLOK C V, RYAN K A, et al. Stress signaling pathways activated by weaning mediate intestinal dysfunction in the pig[J]. American Journal of Physiology:Gastrointestinal and Liver Physiology, 2007, 292(1): G173-G181. DOI:10.1152/ajpgi.00197.2006
[18]
AGUILAR E C, LEONEL A J, TEIXEIRA L G, et al. Butyrate impairs atherogenesis by reducing plaque inflammation and vulnerability and decreasing NFκB activation[J]. Nutrition, Metabolism and Cardiovascular Diseases, 2014, 24(6): 606-613. DOI:10.1016/j.numecd.2014.01.002
[19]
VINOLO M A R, RODRIGUES H G, HATANAKA E, et al. Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils[J]. The Journal of Nutritional Biochemistry, 2011, 22(9): 849-855. DOI:10.1016/j.jnutbio.2010.07.009
[20]
NEUNLIST M, VAN LANDEGHEM L, MAHÉ M M, et al. The digestive neuronal-glial-epithelial unit:a new actor in gut health and disease[J]. Nature Reviews Gastroenterology & Hepatology, 2013, 10(2): 90-100.
[21]
O'LOUGHLIN E V, SCOTT R B, GALL D G. Pathophysiology of infectious diarrhea:changes in intestinal structure and function[J]. Journal of Pediatric Gastroenterology and Nutrition, 1991, 12(1): 5-20. DOI:10.1097/00005176-199101000-00004
[22]
CAMPBELL H K, MAIERS J L, DEMALI K A. Interplay between tight junctions & adherens junctions[J]. Experimental Cell Research, 2017, 358(1): 39-44. DOI:10.1016/j.yexcr.2017.03.061
[23]
YAN H, AJUWON K M. Butyrate modifies intestinal barrier function in IPEC-J2 cells through a selective upregulation of tight junction proteins and activation of the Akt signaling pathway[J]. PLoS One, 2017, 12(6): e0179586. DOI:10.1371/journal.pone.0179586
[24]
罗海祥. 丁酸钠对断奶仔猪生长性能和小肠形态的影响[J]. 畜禽业, 2006(13): 14-16. DOI:10.3969/j.issn.1008-0414.2006.13.003
[25]
王继凤, 陈耀星, 王子旭, 等. 丁酸钠对断奶仔猪小肠黏膜形态结构的影响[J]. 中国兽医科技, 2005, 35(4): 298-301. DOI:10.3969/j.issn.1673-4696.2005.04.011
[26]
ISOLAURI E, SALMINEN S. The impact of early gut microbiota modulation on the risk of child disease:alert to accuracy in probiotic studies[J]. Beneficial Microbes, 2015, 6(2): 167-171. DOI:10.3920/BM2014.0114
[27]
RODRÍGUEZ J M, MURPHY K, STANTON C, et al. The composition of the gut microbiota throughout life, with an emphasis on early life[J]. Microbial Ecology in Health and Disease, 2015, 26(1): 26050.
[28]
WU W, XIAO Z B, AN W Y, et al. Dietary sodium butyrate improves intestinal development and function by modulating the microbial community in broilers[J]. PLoS One, 2018, 13(5): e0197762. DOI:10.1371/journal.pone.0197762
[29]
HOOPER L V, MACPHERSON A J. Immune adaptations that maintain homeostasis with the intestinal microbiota[J]. Nature Reviews Immunology, 2010, 10(3): 159-169. DOI:10.1038/nri2710
[30]
KUCZYNSKI J, STOMBAUGH J, WALTERS W A, et al. Using QIIME to analyze 16S rRNA gene sequences from microbial communities[J]. Current Protocols in Microbiology, 2012, 27(1). DOI:10.1002/9780471729259.mc01e05s27
[31]
DOU S, GADONNA-WIDEHEM P, ROME V, et al. Characterisation of early-life fecal microbiota in susceptible and healthy pigs to post-weaning diarrhoea[J]. PLoS One, 2017, 12(1): e0169851. DOI:10.1371/journal.pone.0169851
[32]
LAOHACHAI K N, BAHADI R, HARDO M B, et al. The role of bacterial and non-bacterial toxins in the induction of changes in membrane transport:implications for diarrhea[J]. Toxicon, 2003, 42(7): 687-707. DOI:10.1016/j.toxicon.2003.08.010
[33]
THOMAS F, HEHEMANN J H, REBUFFET E, et al. Environmental and gut Bacteroidetes:the food connection[J]. Frontiers in Microbiology, 2011, 2: 93.
[34]
LOOFT T, JOHNSON T A, ALLEN H K, et al. In-feed antibiotic effects on the swine intestinal microbiome[J]. Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(5): 1691-1696. DOI:10.1073/pnas.1120238109
[35]
李虹瑾, 沙万里, 尹柏双, 等. 包膜丁酸钠对断奶仔猪肠道菌群及生长性能的影响[J]. 家畜生态学报, 2017, 38(9): 30-34. DOI:10.3969/j.issn.1673-1182.2017.09.006
[36]
VAN IMMERSEEL F, FIEVEZ V, DE BUCK J, et al. Microencapsulated short-chain fatty acids in feed modify colonization and invasion early after infection with Salmonella enteritidis in young chickens[J]. Poultry Science, 2004, 83(1): 69-74. DOI:10.1093/ps/83.1.69
[37]
MANZANILLA E G, NOFRARÍAS M, ANGUITA M, et al. Effects of butyrate, avilamycin, and a plant extract combination on the intestinal equilibrium of early-weaned pigs[J]. Journal of Animal Science, 2006, 84(10): 2743-2751. DOI:10.2527/jas.2005-509
[38]
JERZSELE A, SZEKER K, CSIZINSZKY R, et al. Efficacy of protected sodium butyrate, a protected blend of essential oils, their combination, and Bacillus amyloliquefaciens spore suspension against artificially induced necrotic enteritis in broilers[J]. Poultry Science, 2012, 91(4): 837-843. DOI:10.3382/ps.2011-01853
[39]
KAMIMURA D, ISHIHARA K, HIRANO T. IL-6 signal transduction and its physiological roles:the signal orchestration model[J]. Reviews of Physiology, Biochemistry and Pharmacology, 2003, 149: 1-38.