动物肠道菌群的研究进展
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摘要
肠道微生物是由存在于肠道部位的细菌、古菌、真菌、原生动物以及病毒所组成的群体。人们通过对细菌16SrRNA序列进行测序与分析,对动物及其在特定条件下的肠道菌群进行了相关方面的研究并取得了很大的进展。此外,由微生态原理发展而成的益生菌、益生元和合生元等微生态制剂,可维持机体肠道微生物的平衡、提高肠道屏障功能、增强机体免疫力。因此越来越多的微生态制剂应用于畜牧业、水产业中。论文综述了小鼠、犬、猪这三种动物的肠道菌群及其应用的研究进展,旨在为进一步深入了解动物肠道菌群的结构、功能以及促进微生态制剂的应用提供参考。
The intestinal microflora colonized in animal′s gastrointestinal tract are consisted of bacteria,archaea,fungi,protozoa and viruses.Until now,researchers have developed a series of technologies to study the intestinal microflora in kinds of animals by sequencing and analyzing the 16 SrRNA of bacteria,and some great progress have been made in this period.What′s more,a series of microecological agents,such as probiotics,prebiotics and synbiotics,have been developed.It has been demonstrated that they could maintain the balance of intestinal microflora,improve intestinal barrier function,and enhance immunity.For this reason,more and more microecological agents have been applied in animal husbandry and aquaculture.In this article,we reviewed the progress in the research of the intestinal flora on animals,including mouse,dog and swine,as well as the applications of microecological agent,in order to provide some references for the research and application of intestinal microflora in future.
The intestinal microflora colonized in animal′s gastrointestinal tract are consisted of bacteria,archaea,fungi,protozoa and viruses.Until now,researchers have developed a series of technologies to study the intestinal microflora in kinds of animals by sequencing and analyzing the 16 SrRNA of bacteria,and some great progress have been made in this period.What′s more,a series of microecological agents,such as probiotics,prebiotics and synbiotics,have been developed.It has been demonstrated that they could maintain the balance of intestinal microflora,improve intestinal barrier function,and enhance immunity.For this reason,more and more microecological agents have been applied in animal husbandry and aquaculture.In this article,we reviewed the progress in the research of the intestinal flora on animals,including mouse,dog and swine,as well as the applications of microecological agent,in order to provide some references for the research and application of intestinal microflora in future.
引文
[1]Gart EV,Suchodolski JS,Welsh TH Jr,et al.Salmonella typhimurium and multidirectional communication in the gut[J].Front Microbiol,2016(7):1827.
[2]Kuk S,Uyar Y,Karaca S,et al.Microbiota:In health and in sickness,from birth to death[J].Turkiye Parazitol Derg,2016,40(2):97-106.
[3]Ley RE,Hamady M,Lozupone C,et al.Evolution of mammals and their gut microbes[J].Science,2008,320(5883):1647-1651.
[4]Jiang Y,Ogunade IM,Qi S,et al.Effects of the dose and viability of Saccharomyces cerevisiae.1.Diversity of ruminal microbes as analyzed by Illumina MiSeq sequencing and quantitative PCR[J].J Dairy Sci,2017,100(1):325-342.
[5]Pilloni G,Granitsiotis MS,Engel M,et al.Testing the limits of 454pyrotag sequencing:Reproducibility,quantitative assessment and comparison to T-RFLP fingerprinting of aquifer microbes[J].PLoS One,2012,7(7):e40467.
[6]Kakizaki E,Ogura Y,Kozawa S,et al.Detection of diverse aquatic microbes in blood and organs of drowning victims:First metagenomic approach using high-throughput 454-pyrosequencing[J].Forensic Sci Int,2012,220(1/3):135-146.
[7]Turnbaugh PJ.Microbes and diet-induced obesity:Fast,cheap,and out of control[J].Cell Host Microbe,2017,21(3):278-281.
[8]Isolauri E,Salminen S,Rautava S.Early microbe contact and obesity risk:Evidence of causality?[J].J Pediatr Gastroenterol Nutr,2016,63(Suppl 1):S3-S5.
[9]Endesfelder D,Engel M,Zu Castell W.Gut immunity and type 1diabetes:A melange of microbes,diet,and host interactions?[J].Curr Diab Rep,2016,16(7):60.
[10]Dolan KT,Chang EB.Diet,gut microbes,and the pathogenesis of inflammatory bowel diseases[J].Mol Nutr Food Res,2017,61(1).doi:10.1002/mnfr.201600129.
[11]BabickovaJ,Gardlik R.Pathological and therapeutic interactions between bacteriophages,microbes and the host in inflammatory bowel disease[J].World J Gastroenterol,2015,21(40):11321-11330.
[12]Sears CL.A dynamic partnership:Celebrating our gut flora[J].Anaerobe,2005,11(5):247-251.
[13]Kim YS,Kim J,Park SJ.High-throughput 16SrRNA gene sequencing reveals alterations of mouse intestinal microbiota after radiotherapy[J].Anaerobe,2015(33):1-7.
[14]Kreisinger J,CíˇzkováD,Vohánka J,et al.Gastrointestinal microbiota of wild and inbred individuals of two house mouse subspecies assessed using high-throughput parallel pyrosequencing[J].Mol Ecol,2014,23(20):5048-5060.
[15]Weldon L,Abolins S,Lenzi L,et al.The gut microbiota of wild mice[J].PLoS One,2015,10(8):e0134643.
[16]Linnenbrink M,Wang J,Hardouin EA,et al.The role of biogeography in shaping diversity of the intestinal microbiota in house mice[J].Mol Ecol,2013,22(7):1904-1916.
[17]Borenshtein D,Mcbee ME,Schauer DB.Utility of the Citrobacter rodentiuminfection model in laboratory mice[J].Curr Opin Gastroenterol,2008,24(1):32-37.
[18]Mackos AR,Galley JD,Eubank TD,et al.Social stress-enhanced severity of Citrobacter rodentium-induced colitis is CCL2-dependent and attenuated by probiotic Lactobacillus reuteri[J].Mucosal Immunol,2016,9(2):515-526.
[19]Zhou D,Zhang H,Bai Z,et al.Exposure to soil,house dust and decaying plants increases gut microbial diversity and decreases serum immunoglobulin E levels in BALB/c mice[J].Environ Microbiol,2016,18(5):1326-1337.
[20]Heyman-Lindén L,Kotowska D,Sand E,et al.Lingonberries alter the gut microbiota and prevent low-grade inflammation in high-fat diet fed mice[J].Food Nutr Res,2016(60):29993.
[21]Campbell SC,Wisniewski PJ,Noji M,et al.The effect of diet and exercise on intestinal integrity and microbial diversity in mice[J].PLoS One,2016,11(3):e0150502.
[22]Crawford PA,Gordon JI.Microbial regulation of intestinal radiosensitivity[J].Proc Natl Acad Sci U S A,2005,102(37):13254-13259.
[23]Sivieri K,Morales ML,Saad SM,et al.Prebiotic effect of fructooligosaccharide in the simulator of the human intestinal microbial ecosystem(SHIME?Model)[J].J Med Food,2014,17(8):894-901.
[24]Engevik MA,Faletti CJ,Paulmichl M,et al.Prebiotic properties of galursan HF 7K on mouse gut microbiota[J].Cell Physiol Biochem,2013,32(7):96-110.
[25]Sawin EA,De Wolfe TJ,Aktas B,et al.Glycomacropeptide is aprebiotic that reduces Desulfovibrio bacteria,increases cecal short-chain fatty acids,and is anti-inflammatory in mice[J].Am J Physiol Gastrointest Liver Physiol,2015,309(7):G590-G601.
[26]Treven P,Mrak V,Matijasic BB,et al.Administration of probiotics Lactobacillus rhamnosus GG and Lactobacillus gasseri K7during pregnancy and lactation changes mouse mesenteric lymph nodes and mammary gland microbiota[J].J Dairy Sci,2015,98(4):2114-2128.
[27]Everard A,Matamoros S,Geurts L,et al.Saccharomyces boulardii administration changes gut microbiota and reduces hepatic steatosis,low-grade inflammation,and fat mass in obese and type 2diabetic db/db mice[J].MBio,2014,5(3):e01011-01014.
[28]Aktas B,De Wolfe TJ,Tandee K,et al.The effect of Lactobacillus casei 32Gon the mouse cecum microbiota and innate immune response is dose and time dependent[J].PLoS One,2015,10(12):e0145784.
[29]Musilova S,Modrackova N,Hermanova P,et al.Assessment of the synbiotic properites of human milk oligosaccharides and Bifidobacterium longum subsp.infantis in vitro and in humanised mice[J].Benef Microbes,2017,8(2):281-289.
[30]Simeoli R,Mattace Raso G,Lama A,et al.Preventive and therapeutic effects of Lactobacillus paracasei B21060-based synbiotic treatment on gut inflammation and barrier integrity in colitic mice[J].J Nutr,2015,145(6):1202-1210.
[31]Deng P,Swanson KS.Gut microbiota of humans,dogs and cats:Current knowledge and future opportunities and challenges[J].Br J Nutr,2015,113(Suppl):S6-S17.
[32]Suchodolski JS,Markel ME,Garcia-Mazcorro JF,et al.The fecal microbiome in dogs with acute diarrhea and idiopathic inflammatory bowel disease[J].PLoS One,2012,7(12):e51907.
[33]Bell JA,Kopper JJ,Turnbull JA,et al.Ecological characterization of the colonic microbiota of normal and diarrheic dogs[J].Interdiscip Perspect Infect Dis,2008,2008:149694.
[34]Jia J,Frantz N,Khoo C,et al.Investigation of the faecal microbiota associated with canine chronic diarrhoea[J].FEMS Microbiol Ecol,2010,71(2):304-312.
[35]Guard BC,Barr JW,Reddivari L,et al.Characterization of microbial dysbiosis and metabolomic changes in dogs with acute diarrhea[J].PLoS One,2015,10(5):e0127259.
[36]Xenoulis PG,Palculict B,Allenspach K,et al.Molecular-phylogenetic characterization of microbial communities imbalances in the small intestine of dogs with inflammatory bowel disease[J].FEMS Microbiol Ecol,2008,66(3):579-589.
[37]Suchodolski JS,Xenoulis PG,Paddock CG,et al.Molecular analysis of the bacterial microbiota in duodenal biopsies from dogs with idiopathic inflammatory bowel disease[J].Vet Microbiol,2010,142(3/4):394-400.
[38]Suchodolski JS,Dowd SE,Wilke V,et al.16SrRNA gene pyrosequencing reveals bacterial dysbiosis in the duodenum of dogs with idiopathic inflammatory bowel disease[J].PLoS One,2012,7(6):e39333.
[39]Cerquetella M,Spaterna A,Laus F,et al.Inflammatory bowel disease in the dog:Differences and similarities with humans[J].World J Gastroenterol,2010,16(9):1050-1056.
[40]Igarashi H,Maeda S,Ohno K,et al.Effect of oral administration of metronidazole or prednisolone on fecal microbiota in dogs[J].PLoS One,2014,9(9):e107909.
[41]Tursi A,Brandimarte G,Papa A,et al.Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3as adjunctive to a standard pharmaceutical treatment:A double-blind,randomized,placebo-controlled study[J].Am J Gastroenterol,2010,105(10):2218-2227.
[42]Rossi G,Pengo G,Caldin M,et al.Comparison of microbiological,histological,and immunomodulatory parameters in response to treatment with either combination therapy with prednisone and metronidazole or probiotic VSL#3strains in dogs with idiopathic inflammatory bowel disease[J].PLoS One,2014,9(4):e94699:
[43]Segarra S,Martinez-Subiela S,Cerdà-Cuéllar M,et al.Oral chondroitin sulfate and prebiotics for the treatment of canine Inflammatory Bowel Disease:A randomized,controlled clinical trial[J].BMC Vet Res,2016(12):49.
[44]Alain B Pajarillo E,Chae JP,Balolong MP,et al.Assessment of fecal bacterial diversity among healthy piglets during the weaning transition[J].J Gen Appl Microbiol,2014,60(4):140-146.
[45]Kim HB,Isaacson RE.The pig gut microbial diversity:Understanding the pig gut microbial ecology through the next generation high throughput sequencing[J].Vet Microbiol,2015,177(3/4):242-251.
[46]Koh HW,Kim MS,Lee JS,et al.Changes in the swine gut microbiota in response to porcine epidemic diarrhea infection[J].Microbes Environ,2015,30(3):284-287.
[47]Liu S,Zhao L,Zhai Z,et al.Porcine epidemic diarrhea virus infection induced the unbalance of gut microbiota in piglets[J].Curr Microbiol,2015,71(6):643-649.
[48]Langfeldt D,Neulinger SC,Stiesch M,et al.Health-and disease-associated species clusters in complex natural biofilms determine the innate immune response in oral epithelial cells during biofilm maturation[J].FEMS Microbiol Lett,2014,360(2):137-143.
[49]Shin NR,Lee JC,Lee HY,et al.An increase in the Akkermansia spp.population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice[J].Gut,2014,63(5):727-735.
[50]Li XQ,Zhu YH,Zhang HF,et al.Risks associated with highdose Lactobacillus rhamnosus in an Escherichia coli model of piglet diarrhoea:Intestinal microbiota and immune imbalances[J].PLoS One,2012,7(7):e40666.
[51]Gao Y,Han F,Huang X,et al.Changes in gut microbial populations,intestinal morphology,expression of tight junction proteins,and cytokine production between two pig breeds after challenge with Escherichia coli K88:A comparative study[J].J Anim Sci,2013,91(12):5614-5625.
[52]Schierack P,Nordhoff M,Pollmann M,et al.Characterization of a porcine intestinal epithelial cell line for in vitro studies of microbial pathogenesis in swine[J].Histochem Cell Biol,2006,125(3):293-305.
[53]Samanta AK,Jayaram C,Jayapal N,et al.Assessment of fecal microflora changes in pigs supplemented with herbal residue and prebiotic[J].PLoS One,2015,10(7):e0132961.
[54]Quilodrán-Vega,Villena J,Valdebenito J,et al.Isolation of lactic acid bacteria from swine milk and characterization of potential probiotic strains with antagonistic effects against swineassociated gastrointestinal pathogens[J].Can J Microbiol,2016,62(6):514-524.
[55]Wang Z,Wang L,Chen Z,et al.In vitro evaluation of swinederived Lactobacillus reuteri:Probiotic properties and effects on intestinal porcine epithelial cells challenged with enterotoxigenic Escherichia coli K88[J].J Microbiol Biotechnol,2016,26(6):1018-1025.
[56]Cousin FJ,Foligne B,Deutsch SM,et al.Assessment of the probiotic potential of a dairy product fermented by Propionibacterium freudenreichii in piglets[J].J Agr Food Chem,2012,60(32):7917-7927.
[57]Chu GM,Lee SJ,Jeong HS,et al.Efficacy of probiotics from anaerobic microflora with prebiotics on growth performance and noxious gas emission in growing pigs[J].Anim Sci J,2011,82(2):282-290.
[58]Upadrasta A,O′sullivan L,O′sullivan O,et al.The effect of dietary supplementation with spent cider yeast on the swine distal gut microbiome[J].PLoS One,2013,8(10):e75714.
[59]Bednorz C,Guenther S,Oelgeschlaeger K,et al.Feeding the probiotic Enterococcus faecium strain NCIMB 10415to piglets specifically reduces the number of Escherichia coli pathotypes that adhere to the gut mucosa[J].Appl Environ Microbiol,2013,79(24):7896-7904.
[2]Kuk S,Uyar Y,Karaca S,et al.Microbiota:In health and in sickness,from birth to death[J].Turkiye Parazitol Derg,2016,40(2):97-106.
[3]Ley RE,Hamady M,Lozupone C,et al.Evolution of mammals and their gut microbes[J].Science,2008,320(5883):1647-1651.
[4]Jiang Y,Ogunade IM,Qi S,et al.Effects of the dose and viability of Saccharomyces cerevisiae.1.Diversity of ruminal microbes as analyzed by Illumina MiSeq sequencing and quantitative PCR[J].J Dairy Sci,2017,100(1):325-342.
[5]Pilloni G,Granitsiotis MS,Engel M,et al.Testing the limits of 454pyrotag sequencing:Reproducibility,quantitative assessment and comparison to T-RFLP fingerprinting of aquifer microbes[J].PLoS One,2012,7(7):e40467.
[6]Kakizaki E,Ogura Y,Kozawa S,et al.Detection of diverse aquatic microbes in blood and organs of drowning victims:First metagenomic approach using high-throughput 454-pyrosequencing[J].Forensic Sci Int,2012,220(1/3):135-146.
[7]Turnbaugh PJ.Microbes and diet-induced obesity:Fast,cheap,and out of control[J].Cell Host Microbe,2017,21(3):278-281.
[8]Isolauri E,Salminen S,Rautava S.Early microbe contact and obesity risk:Evidence of causality?[J].J Pediatr Gastroenterol Nutr,2016,63(Suppl 1):S3-S5.
[9]Endesfelder D,Engel M,Zu Castell W.Gut immunity and type 1diabetes:A melange of microbes,diet,and host interactions?[J].Curr Diab Rep,2016,16(7):60.
[10]Dolan KT,Chang EB.Diet,gut microbes,and the pathogenesis of inflammatory bowel diseases[J].Mol Nutr Food Res,2017,61(1).doi:10.1002/mnfr.201600129.
[11]BabickovaJ,Gardlik R.Pathological and therapeutic interactions between bacteriophages,microbes and the host in inflammatory bowel disease[J].World J Gastroenterol,2015,21(40):11321-11330.
[12]Sears CL.A dynamic partnership:Celebrating our gut flora[J].Anaerobe,2005,11(5):247-251.
[13]Kim YS,Kim J,Park SJ.High-throughput 16SrRNA gene sequencing reveals alterations of mouse intestinal microbiota after radiotherapy[J].Anaerobe,2015(33):1-7.
[14]Kreisinger J,CíˇzkováD,Vohánka J,et al.Gastrointestinal microbiota of wild and inbred individuals of two house mouse subspecies assessed using high-throughput parallel pyrosequencing[J].Mol Ecol,2014,23(20):5048-5060.
[15]Weldon L,Abolins S,Lenzi L,et al.The gut microbiota of wild mice[J].PLoS One,2015,10(8):e0134643.
[16]Linnenbrink M,Wang J,Hardouin EA,et al.The role of biogeography in shaping diversity of the intestinal microbiota in house mice[J].Mol Ecol,2013,22(7):1904-1916.
[17]Borenshtein D,Mcbee ME,Schauer DB.Utility of the Citrobacter rodentiuminfection model in laboratory mice[J].Curr Opin Gastroenterol,2008,24(1):32-37.
[18]Mackos AR,Galley JD,Eubank TD,et al.Social stress-enhanced severity of Citrobacter rodentium-induced colitis is CCL2-dependent and attenuated by probiotic Lactobacillus reuteri[J].Mucosal Immunol,2016,9(2):515-526.
[19]Zhou D,Zhang H,Bai Z,et al.Exposure to soil,house dust and decaying plants increases gut microbial diversity and decreases serum immunoglobulin E levels in BALB/c mice[J].Environ Microbiol,2016,18(5):1326-1337.
[20]Heyman-Lindén L,Kotowska D,Sand E,et al.Lingonberries alter the gut microbiota and prevent low-grade inflammation in high-fat diet fed mice[J].Food Nutr Res,2016(60):29993.
[21]Campbell SC,Wisniewski PJ,Noji M,et al.The effect of diet and exercise on intestinal integrity and microbial diversity in mice[J].PLoS One,2016,11(3):e0150502.
[22]Crawford PA,Gordon JI.Microbial regulation of intestinal radiosensitivity[J].Proc Natl Acad Sci U S A,2005,102(37):13254-13259.
[23]Sivieri K,Morales ML,Saad SM,et al.Prebiotic effect of fructooligosaccharide in the simulator of the human intestinal microbial ecosystem(SHIME?Model)[J].J Med Food,2014,17(8):894-901.
[24]Engevik MA,Faletti CJ,Paulmichl M,et al.Prebiotic properties of galursan HF 7K on mouse gut microbiota[J].Cell Physiol Biochem,2013,32(7):96-110.
[25]Sawin EA,De Wolfe TJ,Aktas B,et al.Glycomacropeptide is aprebiotic that reduces Desulfovibrio bacteria,increases cecal short-chain fatty acids,and is anti-inflammatory in mice[J].Am J Physiol Gastrointest Liver Physiol,2015,309(7):G590-G601.
[26]Treven P,Mrak V,Matijasic BB,et al.Administration of probiotics Lactobacillus rhamnosus GG and Lactobacillus gasseri K7during pregnancy and lactation changes mouse mesenteric lymph nodes and mammary gland microbiota[J].J Dairy Sci,2015,98(4):2114-2128.
[27]Everard A,Matamoros S,Geurts L,et al.Saccharomyces boulardii administration changes gut microbiota and reduces hepatic steatosis,low-grade inflammation,and fat mass in obese and type 2diabetic db/db mice[J].MBio,2014,5(3):e01011-01014.
[28]Aktas B,De Wolfe TJ,Tandee K,et al.The effect of Lactobacillus casei 32Gon the mouse cecum microbiota and innate immune response is dose and time dependent[J].PLoS One,2015,10(12):e0145784.
[29]Musilova S,Modrackova N,Hermanova P,et al.Assessment of the synbiotic properites of human milk oligosaccharides and Bifidobacterium longum subsp.infantis in vitro and in humanised mice[J].Benef Microbes,2017,8(2):281-289.
[30]Simeoli R,Mattace Raso G,Lama A,et al.Preventive and therapeutic effects of Lactobacillus paracasei B21060-based synbiotic treatment on gut inflammation and barrier integrity in colitic mice[J].J Nutr,2015,145(6):1202-1210.
[31]Deng P,Swanson KS.Gut microbiota of humans,dogs and cats:Current knowledge and future opportunities and challenges[J].Br J Nutr,2015,113(Suppl):S6-S17.
[32]Suchodolski JS,Markel ME,Garcia-Mazcorro JF,et al.The fecal microbiome in dogs with acute diarrhea and idiopathic inflammatory bowel disease[J].PLoS One,2012,7(12):e51907.
[33]Bell JA,Kopper JJ,Turnbull JA,et al.Ecological characterization of the colonic microbiota of normal and diarrheic dogs[J].Interdiscip Perspect Infect Dis,2008,2008:149694.
[34]Jia J,Frantz N,Khoo C,et al.Investigation of the faecal microbiota associated with canine chronic diarrhoea[J].FEMS Microbiol Ecol,2010,71(2):304-312.
[35]Guard BC,Barr JW,Reddivari L,et al.Characterization of microbial dysbiosis and metabolomic changes in dogs with acute diarrhea[J].PLoS One,2015,10(5):e0127259.
[36]Xenoulis PG,Palculict B,Allenspach K,et al.Molecular-phylogenetic characterization of microbial communities imbalances in the small intestine of dogs with inflammatory bowel disease[J].FEMS Microbiol Ecol,2008,66(3):579-589.
[37]Suchodolski JS,Xenoulis PG,Paddock CG,et al.Molecular analysis of the bacterial microbiota in duodenal biopsies from dogs with idiopathic inflammatory bowel disease[J].Vet Microbiol,2010,142(3/4):394-400.
[38]Suchodolski JS,Dowd SE,Wilke V,et al.16SrRNA gene pyrosequencing reveals bacterial dysbiosis in the duodenum of dogs with idiopathic inflammatory bowel disease[J].PLoS One,2012,7(6):e39333.
[39]Cerquetella M,Spaterna A,Laus F,et al.Inflammatory bowel disease in the dog:Differences and similarities with humans[J].World J Gastroenterol,2010,16(9):1050-1056.
[40]Igarashi H,Maeda S,Ohno K,et al.Effect of oral administration of metronidazole or prednisolone on fecal microbiota in dogs[J].PLoS One,2014,9(9):e107909.
[41]Tursi A,Brandimarte G,Papa A,et al.Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3as adjunctive to a standard pharmaceutical treatment:A double-blind,randomized,placebo-controlled study[J].Am J Gastroenterol,2010,105(10):2218-2227.
[42]Rossi G,Pengo G,Caldin M,et al.Comparison of microbiological,histological,and immunomodulatory parameters in response to treatment with either combination therapy with prednisone and metronidazole or probiotic VSL#3strains in dogs with idiopathic inflammatory bowel disease[J].PLoS One,2014,9(4):e94699:
[43]Segarra S,Martinez-Subiela S,Cerdà-Cuéllar M,et al.Oral chondroitin sulfate and prebiotics for the treatment of canine Inflammatory Bowel Disease:A randomized,controlled clinical trial[J].BMC Vet Res,2016(12):49.
[44]Alain B Pajarillo E,Chae JP,Balolong MP,et al.Assessment of fecal bacterial diversity among healthy piglets during the weaning transition[J].J Gen Appl Microbiol,2014,60(4):140-146.
[45]Kim HB,Isaacson RE.The pig gut microbial diversity:Understanding the pig gut microbial ecology through the next generation high throughput sequencing[J].Vet Microbiol,2015,177(3/4):242-251.
[46]Koh HW,Kim MS,Lee JS,et al.Changes in the swine gut microbiota in response to porcine epidemic diarrhea infection[J].Microbes Environ,2015,30(3):284-287.
[47]Liu S,Zhao L,Zhai Z,et al.Porcine epidemic diarrhea virus infection induced the unbalance of gut microbiota in piglets[J].Curr Microbiol,2015,71(6):643-649.
[48]Langfeldt D,Neulinger SC,Stiesch M,et al.Health-and disease-associated species clusters in complex natural biofilms determine the innate immune response in oral epithelial cells during biofilm maturation[J].FEMS Microbiol Lett,2014,360(2):137-143.
[49]Shin NR,Lee JC,Lee HY,et al.An increase in the Akkermansia spp.population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice[J].Gut,2014,63(5):727-735.
[50]Li XQ,Zhu YH,Zhang HF,et al.Risks associated with highdose Lactobacillus rhamnosus in an Escherichia coli model of piglet diarrhoea:Intestinal microbiota and immune imbalances[J].PLoS One,2012,7(7):e40666.
[51]Gao Y,Han F,Huang X,et al.Changes in gut microbial populations,intestinal morphology,expression of tight junction proteins,and cytokine production between two pig breeds after challenge with Escherichia coli K88:A comparative study[J].J Anim Sci,2013,91(12):5614-5625.
[52]Schierack P,Nordhoff M,Pollmann M,et al.Characterization of a porcine intestinal epithelial cell line for in vitro studies of microbial pathogenesis in swine[J].Histochem Cell Biol,2006,125(3):293-305.
[53]Samanta AK,Jayaram C,Jayapal N,et al.Assessment of fecal microflora changes in pigs supplemented with herbal residue and prebiotic[J].PLoS One,2015,10(7):e0132961.
[54]Quilodrán-Vega,Villena J,Valdebenito J,et al.Isolation of lactic acid bacteria from swine milk and characterization of potential probiotic strains with antagonistic effects against swineassociated gastrointestinal pathogens[J].Can J Microbiol,2016,62(6):514-524.
[55]Wang Z,Wang L,Chen Z,et al.In vitro evaluation of swinederived Lactobacillus reuteri:Probiotic properties and effects on intestinal porcine epithelial cells challenged with enterotoxigenic Escherichia coli K88[J].J Microbiol Biotechnol,2016,26(6):1018-1025.
[56]Cousin FJ,Foligne B,Deutsch SM,et al.Assessment of the probiotic potential of a dairy product fermented by Propionibacterium freudenreichii in piglets[J].J Agr Food Chem,2012,60(32):7917-7927.
[57]Chu GM,Lee SJ,Jeong HS,et al.Efficacy of probiotics from anaerobic microflora with prebiotics on growth performance and noxious gas emission in growing pigs[J].Anim Sci J,2011,82(2):282-290.
[58]Upadrasta A,O′sullivan L,O′sullivan O,et al.The effect of dietary supplementation with spent cider yeast on the swine distal gut microbiome[J].PLoS One,2013,8(10):e75714.
[59]Bednorz C,Guenther S,Oelgeschlaeger K,et al.Feeding the probiotic Enterococcus faecium strain NCIMB 10415to piglets specifically reduces the number of Escherichia coli pathotypes that adhere to the gut mucosa[J].Appl Environ Microbiol,2013,79(24):7896-7904.