动物营养学报    2019, Vol. 31 Issue (4): 1478-1484    PDF    
仔猪肠道微生物代谢产物及益生菌的调控作用
朱翠1, 王少磊1, 蒋宗勇1,2, 陈庄1     
1. 广东省农业科学院农业生物基因研究中心, 广州 510640;
2. 广东省农业科学院动物科学研究所, 广州 510640
摘要: 近年来,肠道微生物组成及其代谢产物与宿主生理之间的互作关系成为当前动物营养研究的热点。研究表明,肠道微生物的代谢产物是影响宿主生理的关键执行者,肠道微生物具有调节宿主代谢、免疫、生长发育等作用。本文系统地综述了仔猪肠道微生物组成、代谢产物种类和功能,以及益生菌对仔猪肠道微生物的影响,以期为仔猪营养调控和肠道微生物的研究提供科学依据。
关键词: 代谢产物     肠道微生物     仔猪     益生菌     宿主生理    
Intestinal Microbial Metabolites and Probiotic Regulation in Piglets
ZHU Cui1, WANG Shaolei1, JIANG Zongyong1,2, CHEN Zhuang1     
1. Agro-Biological Gene Research Center, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China;
2. Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China
Abstract: In recent years, the associations between intestinal microbial composition, host diet and host physiology has increasingly attracted the attention in animal nutrition research. Gut microbiota can regulate the metabolism, immunity, growth and development of the host via its metabolites. This article systematically reviews the composition of intestinal microbiota, the types of microbiota metabolites, and the effect of probiotic supplementation on the intestinal microbiota of piglets, in order to provide some guidance for future research and nutritional regulation on the intestinal microbiota in piglets.
Key words: metabolites     intestinal microbiota     piglets     probiotics     host physiology    

肠道是动物最大的消化器官和免疫器官,也是微生物数量和种类最多的部位。肠道微生物与宿主具有密切的互作联系,一方面,宿主给肠道微生物提供稳定的生长环境;另一方面,肠道微生物能帮助宿主消化食物,抵御病原菌,并能产生短链脂肪酸(short chain fatty acids, SCFAs)、胆汁酸和维生素等代谢产物,从而调控宿主的生理健康并影响疾病发展[1]。本文主要就仔猪肠道微生物的组成与分布、肠道微生物代谢产物的种类与作用,以及益生菌对仔猪肠道微生物组成与功能的影响等方面进行综述,以期为仔猪肠道微生物的研究和疾病防治提供科学依据。

1 仔猪肠道微生物

仔猪在出生前胃肠道是无菌的。仔猪在出生后,一些来自于母体产道及环境中特定的兼性厌氧菌(如大肠杆菌和链球菌)就迅速定植于其肠道内,并创造一个缺氧的环境,随后厌氧菌(如拟杆菌、乳酸菌、双歧杆菌和梭菌)开始定植,形成简单的微生物区系[2]。仔猪肠道微生物受宿主遗传背景、饲粮成分和生长环境等影响,仔猪断奶前的肠道微生物以厌氧菌为主,断奶后随着仔猪的生长发育不断发生变化,最终与宿主建立和谐的共生关系[3]。研究认为,仔猪肠道中微生物主要是厌氧菌和兼性厌氧菌,大多数属于拟杆菌门、厚壁菌门、放线菌门、变形菌门和疣微菌门,其中厚壁菌门和拟杆菌门占90%以上[4]。仔猪不同肠段微生物的种类和数量存在显著差异,且管腔微生物和黏膜微生物的种类和数量也存在差异,肠黏膜中普氏菌属、粪球菌属和柔嫩梭菌属要多于肠道内容物[5]。小肠因具有pH、氧含量和抗菌物质的水平高于大肠以及食糜在此滞留时间较短等特点,决定了小肠中微生物以快速生长的兼性厌氧菌(梭菌属和变形杆菌门)为主,并具有较强的耐酸耐胆盐能力,小肠中微生物数量为104~107 CFU/mL[4]。而大肠是肠道中微生物数量最多的部位,以拟杆菌科和梭菌属为主,微生物数量达到了1011 CFU/mL[5]

2 肠道微生物的代谢产物

肠道微生物通过自身代谢和与宿主共代谢产生一系列代谢产物(表 1),如短链脂肪酸、胆汁酸、多胺、吲哚和维生素等,从而影响宿主生理健康[6-8]。目前,通常可以采取气相色谱(GC)、液相色谱(LC)和高效液相色谱(HPLC)等代谢组学方法来检测这些代谢产物。

表 1 肠道微生物的代谢产物及其产生菌 Table 1 Intestinal microbial metabolites and their producing bacteria[6]
2.1 短链脂肪酸

短链脂肪酸是指碳链中碳原子小于6个的有机脂肪酸,其中含有2~6个碳原子的短链脂肪酸又称为挥发性脂肪酸,包括乙酸、丙酸、异丁酸、丁酸、异戊酸和戊酸等,以乙酸、丙酸和丁酸为主(95%),它们主要由小肠不能消化吸收的纤维、少量的蛋白质和肽等营养物质在结肠和盲肠经厌氧微生物的发酵作用产生[9-10]。短链脂肪酸是结肠上皮细胞的主要能源,能为仔猪提供2%~10%的能量。肠道中产生的短链脂肪酸大部分(80%~90%)在结肠被吸收,其中仅一小部分被微生物自身利用,如脱硫肠状菌(Desulfotomaculum spp.)[10-11]。肠道不同部位的短链脂肪酸产生量存在差异,以盲肠和前端结肠短链脂肪酸含量最高(70~140 mmol/L),末端结肠短链脂肪酸含量显著下降(20~40 mmol/L)[1, 11]。研究表明,短链脂肪酸可直接激活肠上皮细胞的G蛋白偶联受体(GPR),包括GPR41、GPR43和GPR109[12],从而在调节仔猪能量利用、肠道运动、细胞增殖、调节肠道微生态平衡方面发挥重要作用。

2.2 胆汁酸

胆汁酸主要在肝脏由胆固醇合成并分泌到胆汁,胆汁酸作为胆汁的重要成分在脂肪代谢中起着重要作用,能有效地增加胆固醇和脂溶性维生素的吸收[13]。按照来源来分,胆汁酸可分为初级胆汁酸和次级胆汁酸。初级胆汁酸是肝细胞直接以胆固醇为原料在胆固醇7α-羟化酶(7α-hydroxylase,CYP7A1)和甾醇-27羟化酶(sterol-27-hydroxylase,CYP27A1)催化合成的胆汁酸,包括胆酸(cholic acid, CA)、鹅脱氧胆酸(chenodeoxycholic acid, CDCA)及相应结合型胆汁酸[14]。初级游离胆汁酸在肠道细菌作用下进一步经胆盐诱导酶的脱羟基作用降解为次级胆汁酸,包括脱氧胆酸(deoxycholic acid, DCA)及石胆酸(lithocholic acid, LCA),它们分别经胆酸和鹅脱氧胆酸通过7α-羟基脱氧后得到[15]。大部分的胆汁酸(90%~95%)在回肠末端被重吸收,并经门静脉到达肝脏进行肠肝循环;剩余的胆汁酸(5%~10%)主要被肠道中多数厌氧微生物(拟杆菌、梭菌、真细菌、乳酸菌、大肠杆菌等)和少数需氧菌(放线菌和变形菌等)分泌的胆盐水解酶(bile salt hydrolase, BSH)水解为初级游离胆汁酸,仅少部分胆汁酸直接随粪便排出体外[7, 15]。大部分次级胆汁酸(如脱氧胆酸)通过回肠上皮细胞中的转运载体吸收或直接经肠道被动吸收,石胆酸的重吸收率较低,大多通过粪便排出体外[16]。胆汁酸的合成和代谢途径见图 1。研究证实,初级和次级胆汁酸分别通过激活法尼醇X受体(FXR)和G蛋白偶联跨膜受体5(TGR5)来调控宿主糖代谢、脂代谢和能量代谢[14]。研究发现,炎症性肠病、肠易激综合征和短肠综合征等临床疾病都与胆汁酸的含量异常相关[15]

黑色箭头表示胆汁酸合成的经典途径,红色箭头表示胆汁酸合成的其他途径。 The black arrows show the classical pathway of bile acid synthesis, and the red arrows show the other pathways of bile acid synthesis. 图 1 胆汁酸的合成和代谢 Fig. 1 Bile acid synthesis and metabolism
2.3 胆碱代谢物

肠道微生物能代谢胆碱产生三甲胺氧化物(trimethylamine oxide, TMO),然后被肝脏的黄素单加氧酶(flavinmonooxygenases,FMOs)代谢产生氧化甲胺(trimethylamine-N-oxide, TMAO)。研究发现,小鼠饲粮中补充TMAO或富含胆碱、肉碱和γ-丁酰甜菜碱能加速血栓的形成[17],并能通过降低CYP7A1的活性减少初级胆汁酸的合成,增加心血管疾病的风险[18]。研究发现,高胆碱饲粮显著增加了小鼠盲肠管腔红蝽杆菌、韦荣球菌和支原体的丰度,这与小鼠体内高水平的TMAO密切相关,研究还发现TMAO是通过调节内源细胞释放钙离子(Ca2+)而过度增加了血小板的活性,可能会增加动脉粥样硬化的疾病风险[19]

2.4 其他代谢物

色氨酸是仔猪生长的必需氨基酸,肠道微生物能代谢色氨酸产生犬尿酸、血清素、褪黑素、吲哚、吲哚酸、粪臭素和色胺等代谢产物,这些代谢产物可通过与芳烃受体(AhR)结合促进宿主免疫稳态[20]。饲粮中有1%~2%的色氨酸可被转化为五羟色胺和褪黑素,其中血清素作为一种神经递质能控制胃肠蠕动、敏感性和分泌并能影响食欲和情绪[20-21]。大肠杆菌(E. coli)能代谢色氨酸产生吲哚,能减少促炎因子白细胞介素-8(IL-8)的表达,增加抗炎因子白细胞介素-10(IL-10)的表达,加强肠上皮屏障功能并减少病原菌的定植[22]。此外,肠道中存在一种特定的细菌——生孢梭菌(Clostridium sporogenes),能特异性代谢芳香族氨基酸产生吲哚丙酸,吲哚丙酸被证明具有降低肠道通透性、调节免疫细胞活性等作用[23]

3 益生菌对仔猪肠道微生物的影响

益生菌是指直接饲喂动物并通过调节动物肠道微生态平衡达到预防疾病、促进生长、提高饲料利用率的活性微生物的总称,主要包括芽孢杆菌、乳酸菌和酵母菌三大类。研究发现,益生菌可能通过与病原菌竞争肠道的黏附位点和营养底物,并通过代谢产生乳酸、乙酸等降低肠道的pH来阻止病原菌定植肠道,还能调节仔猪肠道微生物的群落结构、增加营养物质的代谢能力、控制病原菌等,从而促进仔猪肠道健康[24]

3.1 调节肠道菌群结构和多样性

研究表明,添加酿酒酵母显著增加了断奶前后仔猪盲肠和结肠管腔微生物菌群的丰度,并与盲肠和结肠中多种细菌属存在正相关性[25]。本课题组前期研究也发现,活性干酵母可显著降低早期断奶仔猪回肠和结肠内容物pH,并显著降低其大肠杆菌的数量[26]。屎肠球菌和乳酸菌复合物显著增加了断奶仔猪粪便中乳酸菌的数量,促进了物质代谢和能量代谢,以屎肠球菌的效果更好[27];此外,屎肠球菌还可减少仔猪小肠中大肠杆菌和需氧菌的数量[28]。解淀粉芽孢杆菌能够增加刚出生仔猪回肠管腔中乳酸菌和双歧杆菌的数量,降低空肠管腔中大肠杆菌的数量[29]。研究发现,饲粮中添加婴儿双歧杆菌和乳双歧杆菌能有效降低鼠伤寒沙门氏菌处理的断奶仔猪粪便中沙门氏菌的数量,缓解沙门氏菌的感染[30]。益生性大肠杆菌能分泌小菌素,抑制炎症肠道中沙门氏菌和大肠杆菌的生长,还能缓解沙门氏菌的感染[31]。给猪长期补充屎肠球菌能阻止产肠毒性大肠杆菌(ETEC)对肠道的感染[32]。Trevisi等[33]发现给ETEC K88处理的断奶仔猪补充鼠李糖乳杆菌并不影响仔猪肠道中乳酸菌、酵母菌等数量,却增加了粪便中ETEC的数量,损害了肠道健康。

3.2 调节肠道微生物代谢产物的产生

研究认为,益生菌的部分益生作用与调节肠道菌群产生的代谢产物有关,以短链脂肪酸和胆汁酸的研究报道较多。例如,丁酸梭菌作为丁酸产生菌,能增加断奶仔猪粪便中巨型球菌和霍氏真杆菌的数量,加强乙酸的产生和利用,产生更多的丁酸,从而调节断奶仔猪的肠道健康[34]。在妊娠期和哺乳期给母猪饲粮添加复合益生菌制剂可显著提高仔猪粪便中的短链脂肪酸的含量,同时发现短链脂肪酸产生菌(梭菌群Ⅳ和ⅪⅤa)的丰度也显著升高[35]。本课题组前期也发现,不同品种仔猪的肠道微生物代谢产物(尤其是短链脂肪酸和胆汁酸)存在显著差异,其中生长速度较快的长白仔猪中结肠内容物中短链脂肪酸和次级胆汁酸含量要显著高于生长速度较慢的梅花猪[36]。短链脂肪酸作为信号分子能通过与其GPR受体结合,调节宿主的脂肪酸代谢、糖代谢和胆固醇代谢,还可激活肠道L细胞分泌胰高血糖素样肽(GLP-1),从而调节胰岛素的释放来影响采食与生长[37]。最新研究表明,早期抗生素处理会破坏哺乳仔猪回肠和盲肠的肠道菌群平衡及其代谢稳态,尤其是使得短链脂肪酸产量减少,蛋白质发酵产物产量(如腐胺、尸胺等)增加[38]。但是,给断奶仔猪饲喂复合益生菌EBS(屎肠球菌、芽孢杆菌和酵母菌)显著提高了仔猪粪便中乙酸和丙酸的含量,而复合益生菌EBL(屎肠球菌、芽孢杆菌和副干酪乳杆菌)显著提高了仔猪粪便中乙酸、丙酸、丁酸和戊酸的含量,从而提高断奶仔猪的生产性能并降低腹泻率[39]

此外,研究还表明,口服胆汁酸结合能力强的益生菌[如乳酸乳球菌(Lactococcus lactis)],可促进胆汁酸的在小肠的解离,从而促进解离的胆汁酸在大肠重吸收效率[40]。植物乳杆菌可以显著上调小鼠CYP7A1基因的表达水平,同时增加小鼠粪便中胆汁酸的排泄,从而降低小鼠血清中低密度脂蛋白和甘油三酯的浓度[41]。益生菌可能是通过调节胆盐水解酶(BSH)和胆汁酸诱导酶(BAI)的活性,引起胆汁酸的解离和脱羟基反应,从而调节胆汁酸代谢,进而影响宿主的胆固醇生理代谢过程[42]。此外,胆汁酸也被证实对早期断奶仔猪的肠道完整性和生长性能具有改善作用[43]

4 小结

肠道是微生物、营养物质与免疫细胞充分接触的场所,肠道微生物具有消化和发酵碳水化合物、维持肠道正常功能、调节免疫、竞争抑制病原菌等益生作用, 从而调控仔猪生长,这些作用可能是肠道微生物产生特定的小分子代谢产物作为下游信号分子与宿主受体结合来实现的。通过微生物组学、宏基因组学和代谢组学技术可研究肠道微生物和代谢产物的变化,并通过生物信息学手段可分析肠道微生物和宿主表型相关性,但肠道微生物及其代谢产物如何影响宿主代谢,尤其是对关键功能菌的鉴定和影响宿主表型的关键代谢物的筛选仍比较困难。目前对于仔猪肠道代谢产物与宿主健康关系的研究仍处于起步阶段,因此,利用无菌动物模型和多组学联用手段全面剖析肠道微生物及其代谢产物的变化,以及对宿主表型的因果关系研究是未来肠道微生物研究的重要方向。

参考文献
[1]
KOH A, DE VADDER F, KOVATCHEVA-DATCHARY P, et al. From dietary fiber to host physiology:short-chain fatty acids as key bacterial metabolites[J]. Cell, 2016, 165(6): 1332-1345. DOI:10.1016/j.cell.2016.05.041
[2]
GRESSE R, CHAUCHEYRAS-DURAND F, FLEURY M A, et al. Gut microbiota dysbiosis in postweaning piglets:understanding the keys to health[J]. Trends in Microbiology, 2017, 25(10): 851-873. DOI:10.1016/j.tim.2017.05.004
[3]
CHEN X, XU J M, REN E D, et al. Co-occurrence of early gut colonization in neonatal piglets with microbiota in the maternal and surrounding delivery environments[J]. Anaerobe, 2018, 49: 30-40. DOI:10.1016/j.anaerobe.2017.12.002
[4]
DONALDSON G P, LEE S M, MAZMANIAN S K. Gut biogeography of the bacterial microbiota[J]. Nature Reviews Microbiology, 2016, 14(1): 20-32. DOI:10.1038/nrmicro3552
[5]
KELLY J, DALY K, MORAN A W, et al. Composition and diversity of mucosa-associated microbiota along the entire length of the pig gastrointestinal tract; dietary influences[J]. Environmental Microbiology, 2017, 19(4): 1425-1438. DOI:10.1111/1462-2920.13619
[6]
NICHOLSON J K, HOLMES E, KINROSS J, et al. Host-gut microbiota metabolic interactions[J]. Science, 2012, 336(6086): 1262-1267. DOI:10.1126/science.1223813
[7]
YAN S J, HUANG J F, CHEN Z J, et al. Metabolomics in gut microbiota:applications and challenges[J]. Science Bulletin, 2016, 61(15): 1151-1153. DOI:10.1007/s11434-016-1142-7
[8]
KHATIBJOO A, MAHMOODI M, FATTAHNIA F, et al. Effects of dietary short-and medium-chain fatty acids on performance, carcass traits, jejunum morphology, and serum parameters of broiler chickens[J]. Journal of Applied Animal Research, 2017, 46(1): 492-498.
[9]
OHIRA H, TSUTSUI W, FUJIOKA Y. Are short chain fatty acids in gut microbiota defensive players for inflammation and atherosclerosis?[J]. Journal of Atherosclerosis and Thrombosis, 2017, 24(7): 660-672. DOI:10.5551/jat.RV17006
[10]
WANG L L, GUO H H, HUANG S, et al. Comprehensive evaluation of SCFA production in the intestinal bacteria regulated by berberine using gas-chromatography combined with polymerase chain reaction[J]. Journal of Chromatography B, 2017, 1057: 70-80. DOI:10.1016/j.jchromb.2017.05.004
[11]
TURRONI S, BRIGIDI P, CAVALLI A, et al. Microbiota-host transgenomic metabolism, bioactive molecules from the inside[J]. Journal of Medicinal Chemistry, 2018, 61(1): 47-61.
[12]
HUSTED A S, TRAUELSEN M, RUDENKO O, et al. GPCR-mediated signaling of metabolites[J]. Cell Metabolism, 2017, 25(4): 777-796. DOI:10.1016/j.cmet.2017.03.008
[13]
SHAPIRO H, KOLODZIEJCZYK A A, HALSTUCH D, et al. Bile acids in glucose metabolism in health and disease[J]. The Journal of Experimental Medicine, 2018, 215(2): 383-396. DOI:10.1084/jem.20171965
[14]
WAHLSTRÖM A, SAYIN S I, MARSCHALL H U, et al. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism[J]. Cell Metabolism, 2016, 24(1): 41-50. DOI:10.1016/j.cmet.2016.05.005
[15]
LONG S L, GAHAN C G M, JOYCE S A. Interactions between gut bacteria and bile in health and disease[J]. Molecular Aspects of Medicine, 2017, 56: 54-65. DOI:10.1016/j.mam.2017.06.002
[16]
GHAFFARZADEGAN T, ZHONG Y D, FAK HÅLLENIUS F, et al. Effects of barley variety, dietary fiber and β-glucan content on bile acid composition in cecum of rats fed low-and high-fat diets[J]. The Journal of Nutritional Biochemistry, 2018, 53: 104-110. DOI:10.1016/j.jnutbio.2017.10.008
[17]
WANG Z N, KLIPFELL E, BENNETT B J, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease[J]. Nature, 2011, 472(7341): 57-63. DOI:10.1038/nature09922
[18]
KOETH R A, WANG Z N, LEVISON B S, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis[J]. Nature Medicine, 2013, 19(5): 576-585. DOI:10.1038/nm.3145
[19]
ZHU W F, GREGORY J C, ORG E, et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis Risk[J]. Cell, 2016, 165(1): 111-124. DOI:10.1016/j.cell.2016.02.011
[20]
GAO J, XU K, LIU H N, et al. Impact of the gut microbiota on intestinal immunity mediated by tryptophan metabolism[J]. Frontiers in Cellular and Infection Microbiology, 2018, 8: 13. DOI:10.3389/fcimb.2018.00013
[21]
ZELANTE T, IANNITTI R G, CUNHA C, et al. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22[J]. Immunity, 2013, 39(2): 372-385. DOI:10.1016/j.immuni.2013.08.003
[22]
BANSAL T, ALANIZ R C, WOOD T K, et al. The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation[J]. Proceedings of the National Academy of Sciences of the United States of America, 2010, 107(1): 228-233. DOI:10.1073/pnas.0906112107
[23]
DODD D, SPITZER M H, VAN TREUREN W, et al. A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites[J]. Nature, 2017, 551(7682): 648-652. DOI:10.1038/nature24661
[24]
LIU Y H, ESPINOSA C D, ABELILLA J J, et al. Non-antibiotic feed additives in diets for pigs:a review[J]. Animal Nutrition, 2018, 4(2): 113-125. DOI:10.1016/j.aninu.2018.01.007
[25]
KIROS T G, DERAKHSHANI H, PINLOCHE E, et al. Effect of live yeast Saccharomyces cerevisiae (Actisaf Sc 47) supplementation on the performance and hindgut microbiota composition of weanling pigs[J]. Scientific Reports, 2018, 8(1): 5315. DOI:10.1038/s41598-018-23373-8
[26]
ZHU C, WANG L, WEI S Y, et al. Effect of yeast Saccharomyces cerevisiae supplementation on serum antioxidant capacity, mucosal sIgA secretions and gut microbial populations in weaned piglets[J]. Journal of Integrative Agriculture, 2017, 16(9): 2029-2037. DOI:10.1016/S2095-3119(16)61581-2
[27]
ZHAO P Y, ZHANG Z F, LAN R X, et al. Comparison of efficacy of lactic acid bacteria complex and Enterococcus faecium DSM 7134 in weanling pigs[J]. Journal of Applied Animal Research, 2018, 46(1): 888-892. DOI:10.1080/09712119.2017.1420655
[28]
XIE Y H, ZHANG C Y, WANG L X, et al. Effects of dietary supplementation of Enterococcus faecium on growth performance, intestinal morphology, and selected microbial populations of piglets[J]. Livestock Science, 2018, 210: 111-117. DOI:10.1016/j.livsci.2018.02.010
[29]
LI Y, ZHANG H, SU W P, et al. Effects of dietary Bacillus amyloliquefaciens supplementation on growth performance, intestinal morphology, inflammatory response, and microbiota of intra-uterine growth retarded weanling piglets[J]. Journal of Animal Science and Biotechnology, 2018, 9: 22. DOI:10.1186/s40104-018-0236-2
[30]
BARBA-VIDAL E, CASTILLEJOS L, ROLL V F B, et al. The probiotic combination of Bifidobacterium longum subsp.lactis BPL6 reduces pathogen loads and improves gut health of weaned piglets orally challenged with Salmonella Typhimurium[J]. Frontiers in Microbiology, 2017, 8: 1570. DOI:10.3389/fmicb.2017.01570
[31]
SASSONE-CORSI M, NUCCIO S P, LIU P, et al. Microcins mediate competition among Enterobacteriaceae in the inflamed gut[J]. Nature, 2016, 540(7632): 280-283. DOI:10.1038/nature20557
[32]
KERN M, ASCHENBACH J R, TEDIN K, et al. Characterization of inflammasome components in pig intestine and analysis of the influence of probiotic Enterococcus Faecium during an Escherichia coli challenge[J]. Immunological Investigations, 2017, 46(7): 742-757. DOI:10.1080/08820139.2017.1360341
[33]
TREVISI P, CASINI L, COLORETTI F, et al. Dietary addition of Lactobacillus rhamnosus GG impairs the health of Escherichia coli F4-challenged piglets[J]. Animal, 2011, 5(9): 1354-1360. DOI:10.1017/S1751731111000462
[34]
ZHANG J, CHEN X Y, LIU P, et al. Dietary Clostridium butyricum induces a phased shift in fecal microbiota structure and increases the acetic acid-producing bacteria in a weaned piglet model[J]. Journal of Agricultural and Food Chemistry, 2018, 66(20): 5157-5166. DOI:10.1021/acs.jafc.8b01253
[35]
MORI K, ITO T, MIYAMOTO H, et al. Oral administration of multispecies microbial supplements to sows influences the composition of gut microbiota and fecal organic acids in their post-weaned piglets[J]. Journal of Bioscience and Bioengineering, 2011, 112(2): 145-150. DOI:10.1016/j.jbiosc.2011.04.009
[36]
YAN S J, ZHU C, YU T, et al. Studying the differences of bacterial metabolome and microbiome in the colon between Landrace and Meihua piglets[J]. Frontiers in Microbiology, 2017, 8: 1812. DOI:10.3389/fmicb.2017.01812
[37]
TOLHURST G, HEFFRON H, LAM Y S, et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2[J]. Diabetes, 2012, 61(2): 364-371. DOI:10.2337/db11-1019
[38]
YU M, MU C L, ZHANG C J, et al. Marked response in microbial community and metabolism in the ileum and cecum of suckling piglets after early antibiotics exposure[J]. Frontiers in Microbiology, 2018, 9: 1166. DOI:10.3389/fmicb.2018.01166
[39]
LU X, ZHANG M, ZHAO L, et al. Growth performance and post-weaning diarrhoea in piglets fed a diet supplemented with probiotic complexes[J]. Journal of Microbiology and Biotechnology, 2018. DOI:10.4014/jmb.1807.07026
[40]
JIA W, XIE G X. Probiotics, bile acids and gastrointestinal carcinogenesis[J]. Nature Reviews Gastroenterology & Hepatology, 2018, 15(4): 205.
[41]
JEUN J, KIM S, CHO S Y, et al. Hypocholesterolemic effects of Lactobacillus plantarum KCTC3928 by increased bile acid excretion in C57BL/6 mice[J]. Nutrition, 2010, 26(3): 321-330. DOI:10.1016/j.nut.2009.04.011
[42]
PAVLOVIĆ N, STANKOV K, MIKOV M. Probiotics-interactions with bile acids and impact on cholesterol metabolism[J]. Applied Biochemistry and Biotechnology, 2012, 168(7): 1880-1895. DOI:10.1007/s12010-012-9904-4
[43]
DE DIEGO-CABERO N, MEREU A, MENOYO D, et al. Bile acid mediated effects on gut integrity and performance of early-weaned piglets[J]. BMC Veterinary Research, 2015, 11: 111. DOI:10.1186/s12917-015-0425-6