畜禽粪污源抗生素及耐药基因在环境中的归趋
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摘要
抗生素因具有促进动物生长、提高饲料转化效率、预防治疗动物疾病等作用而被大量用于畜牧业。然而仅有少量抗生素可被动物吸收降解,其余大部分抗生素以原型或有抗菌活性的代谢产物的形式通过粪尿排入环境。除抗生素外,动物粪便中还含有大量的耐药细菌,是巨大的耐药基因(antibiotic resistance genes,ARGs)库。残留于动物粪便中的抗生素和耐药基因通过动物粪便的施用而在环境中传播,并且残留的抗生素能进一步富集环境中的耐药基因。这对人类健康及生态系统存在着潜在危害。基于此,对畜禽粪污源抗生素及耐药基因在环境中的归趋进行综述,以期为研究畜禽粪污源抗生素及耐药基因对生态系统及人类健康的危害提供科学参考。
Antibiotics are widely used in animal husbandry due to their outstanding functions, including promoting animal growth, improving feed conversion efficiency, and preventing and treating animal diseases. However, only a small amount of antibiotics can be absorbed and degraded by animals, and most of the ingested veterinary antibiotics are excreted into the environment through feces and urine in the form of prototype or antibacterial metabolites. Apart from antibiotics, manure is also a reservoir of antibiotic resistance genes(ARGs) which contains numerous antibiotic resistant bacteria. Antibiotics and ARGs in the manure can transmit in the environment with the application of manure. Furthermore, residual antibiotics can further enrich ARGs in the environment. It has the potential harm to the human health and ecosystem. Based on this situation, environmental fate of antibiotics and ARGs in animal manure was summarized in order to provide a scientific reference for studying the harm of antibiotics and ARGs to ecosystem and human health.
Antibiotics are widely used in animal husbandry due to their outstanding functions, including promoting animal growth, improving feed conversion efficiency, and preventing and treating animal diseases. However, only a small amount of antibiotics can be absorbed and degraded by animals, and most of the ingested veterinary antibiotics are excreted into the environment through feces and urine in the form of prototype or antibacterial metabolites. Apart from antibiotics, manure is also a reservoir of antibiotic resistance genes(ARGs) which contains numerous antibiotic resistant bacteria. Antibiotics and ARGs in the manure can transmit in the environment with the application of manure. Furthermore, residual antibiotics can further enrich ARGs in the environment. It has the potential harm to the human health and ecosystem. Based on this situation, environmental fate of antibiotics and ARGs in animal manure was summarized in order to provide a scientific reference for studying the harm of antibiotics and ARGs to ecosystem and human health.
引文
[1] Zhang Q Q, Ying G G, Pan C G, et al.. Comprehensive evaluation of antibiotics emission and fate in the river basins of China: Source analysis, multimedia modeling, and linkage to bacterial resistance[J]. Environ. Sci. Technol., 2015, 49(11): 6772-6782.
[2] Lienert J, Gudel K, Escher B I. Screening method for ecotoxicological hazard assessment of 42 pharmaceuticals considering human metabolism and excretory routes[J]. Environ. Sci. Technol., 2007, 41(12): 4471-4478.
[3] Sarmaha A K, Meyer M T, Boxallo A B A. A Global perspective on the use, sales, exposure pathways, occurrence, fate and effects of veterinary antibiotics (VAs) in the environment[J]. Chemosphere, 2006, 65(5): 725-759.
[4] Hirsch R, Ternes T, Haberer K, et al.. Occurrence of antibiotics in the aquatic environment[J]. Sci. Total Environ., 1999, 225(1): 109-118.
[5] Hu X, Zhou Q, Luo Y. Occurrence and source analysis of typical veterinary antibiotics in manure, soil, vegetables and groundwater from organic vegetable bases, Northern China[J]. Environ. Pollut., 2010, 158(9): 2992-2998.
[6] Selvam A, Xu D, Zhao Z, et al.. Fate of tetracycline, sulfonamide and fluoroquinolone resistance genes and the changes in bacterial diversity during composting of swine manure[J]. Bioresource Technol., 2012, 126: 383-390.
[7] Colomer-Lluch M, Imamovic L, Jofre J, et al.. Bacteriophages carrying antibiotic resistance genes in fecal waste from cattle, pigs, and poultry[J]. Antimicrob. Agents Chemoth., 2011, 55(10): 4908-4911.
[8] Ji X, Shen Q, Liu F, et al.. Antibiotic resistance gene abundances associated with antibiotics and heavy metals in animal manures and agricultural soils adjacent to feedlots in Shanghai China[J]. J. Hazard. Mater., 2012, 235: 178-185.
[9] Ma L, Xia Y, Li B, et al.. Metagenomic assembly reveals hosts of antibiotic resistance genes and the shared resistome in pig, chicken, and human feces[J]. Environ. Sci. Technol., 2015, 50(1): 420-427.
[10] Luo Y, Mao D, Rysz M, et al.. Trends in antibiotic resistance genes occurrence in the Haihe River, China[J]. Environ. Sci. Technol., 2010, 44(19): 7220-7225.
[11] Su H C, Ying G G, Tao R, et al.. Class 1 and 2 integrons, sul resistance genes and antibiotic resistance in Escherichia coli isolated from Dongjiang River, South China[J]. Environ. Pollut., 2012, 169: 42-49.
[12] Phillips I, Casewell M, Cox T, et al.. Does the use of antibiotics in food animals pose a risk to human health? A critical review of published data[J]. J. Antimicrob. Chemoth., 2004, 53(1): 28-52.
[13] Miller G Y, Algozin K A, Mcnamara P E, et al.. Productivity and economic effects of antibiotics used for growth promotion in US pork production[J]. J. Agric. Appl. Econ., 2003, 35(3): 469-482.
[14] 贺德春, 许振成, 吴根义, 等. 四环素类抗生素的环境行为研究进展[J]. 动物医学进展, 2011, 32(4):98-102.
[15] Zhao L, Dong Y H, Wang H. Residues of veterinary antibiotics in manures from feedlot livestock in eight provinces of China[J]. Sci. Total Environ., 2010, 408(5): 1069-1075.
[16] Hu X G, Luo Y, Zhou Q X, et al.. Determination of thirteen antibiotics residues in manure by solid phase extraction and high performance liquid chromatography[J]. Chin. J. Anal. Chem., 2008, 36(9): 1162-1166.
[17] Qiao M, Chen W, Su J, et al.. Fate of tetracyclines in swine manure of three selected swine farms in China[J]. J. Environ. Sci. China, 2012, 24(6): 1047-1052.
[18] Hou J, Wan W, Mao D, et al.. Occurrence and distribution of sulfonamides, tetracyclines, quinolones, macrolides, and nitrofurans in livestock manure and amended soils of Northern China[J]. Environ. Sci. Pollut. R., 2015, 22(6): 4545-4554.
[19] Wang N, Guo X, Xu J, et al.. Pollution characteristics and environmental risk assessment of typical veterinary antibiotics in livestock farms in Southeastern China[J]. J. Environ. Sci. Health B, 2014, 49(7): 468-479.
[20] Zhang H, Luo Y, Wu L, et al.. Residues and potential ecological risks of veterinary antibiotics in manures and composts associated with protected vegetable farming[J]. Environ. Sci. Pollut. R., 2015, 22(8): 5908-5918.
[21] Li Y, Zhang X, Li W, et al.. The residues and environmental risks of multiple veterinary antibiotics in animal faeces[J]. Environ. Monit. Assess., 2013, 185(3): 2211-2220.
[22] He L Y, Ying G G, Liu Y S, et al.. Discharge of swine wastes risks water quality and food safety: Antibiotics and antibiotic resistance genes from swine sources to the receiving environments[J]. Environ. Int., 2016, 92: 210-219.
[23] 广东省统计局. 2018年广东统计年鉴[M]. 北京: 中国统计出版社, 2018.
[24] Xu W, Zhang G, Zou S, et al.. Determination of selected antibiotics in the Victoria Harbour and the Pearl River, South China using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry[J]. Environ. Pollut., 2007, 145(3): 672-679.
[25] Wei R, Ge F, Huang S, et al.. Occurrence of veterinary antibiotics in animal wastewater and surface water around farms in Jiangsu Province, China[J]. Chemosphere, 2011, 82(10): 1408-1414.
[26] Xu W, Zhang G, Zou S, et al.. A preliminary investigation on the occurrence and distribution of antibiotics in the Yellow River and its tributaries, China[J]. Water Environ. Res., 2009, 81(3): 248-254.
[27] Li W, Shi Y, Gao L, et al.. Occurrence of antibiotics in water, sediments, aquatic plants, and animals from Baiyangdian Lake in North China[J]. Chemosphere, 2012, 89(11): 1307-1315.
[28] Tao R, Ying G G, Su H C, et al.. Detection of antibiotic resistance and tetracycline resistance genes in enterobacteriaceae isolated from the Pearl Rivers in South China[J]. Environ. Pollut., 2010, 158(6): 2101-2109.
[29] Jiang L, Hu X, Xu T, et al.. Prevalence of antibiotic resistance genes and their relationship with antibiotics in the Huangpu River and the drinking water sources, Shanghai, China[J]. Sci. Total Environ., 2013, 458: 267-272.
[30] Zhou L J, Ying G G, Zhao J L, et al.. Trends in the occurrence of human and veterinary antibiotics in the sediments of the Yellow River, Hai River and Liao River in Northern China[J]. Environ. Pollut., 2011, 159(7): 1877-1885.
[31] Davies J. Origins and evolution of antibiotic resistance[J]. Microbiol. Mol. Biol. Rev., 1996, 12(1): 9-16.
[32] Wright G D. The antibiotic resistome: The nexus of chemical and genetic diversity[J]. Nat. Rev. Microbiol., 2007, 5(3): 175-186.
[33] Kruse H, S?rum H. Transfer of multiple drug resistance plasmids between bacteria of diverse origins in natural microenvironments[J]. Appl. Environ. Microbiol., 1994, 60(11): 4015-4021.
[34] Gillings M R, Stokes H W. Are humans increasing bacterial evolvability?[J]. Trends Ecol. Evol., 2012, 27(6): 346-352.
[35] Heuer H, Schmitt H, Smalla K. Antibiotic resistance gene spread due to manure application on agricultural fields[J]. Curr. Opin. Microbiol., 2011, 14(3): 236-243.
[36] Conde C M, álvarez E C, Paradelo N R, et al.. Occurrence of tetracyclines and sulfonamides in manures, agricultural soils and crops from different areas in Galicia (NW Spain) [J]. J. Clean. Prod., 2018, 197: 491-500.
[37] Zhao F, Yang L, Chen L, et al.. Bioaccumulation of antibiotics in crops under long-term manure application: Occurrence, biomass response and human exposure[J]. Chemosphere, 2019, 219: 882-895.
[38] 刘晓瑜, 马玉超. 抗耐药细菌药用植物内生菌的筛选与鉴定[J]. 生物技术通报, 2015, 31(3):154-160.
[39] Wang F H, Qiao M, Chen Z, et al.. Antibiotic resistance genes in manure-amended soil and vegetables at harvest[J]. J. Hazard. Mater., 2015, 299: 215-221.
[40] Yang Q, Ren S, Niu T, et al.. Distribution of antibiotic-resistant bacteria in chicken manure and manure-fertilized vegetables[J]. Environ. Sci. Pollut. Res., 2014, 21(2): 1231-1241.
[41] Marti R, Scott A, Tien Y C, et al.. Impact of manure fertilization on the abundance of antibiotic-resistant bacteria and frequency of detection of antibiotic resistance genes in soil and on vegetables at harvest[J]. Appl. Environ. Microbiol., 2013, 79(18): 5701-5709.
[42] Kuppusamy S, Kakarla D, Venkateswarlu K, et al.. Veterinary antibiotics (VAs) contamination as a global agro-ecological issue: A critical view[J]. Agric. Ecosyst. Environ., 2018, 257: 47-59.
[43] Dancer S J. How Antibiotics can make us sick: The less obvious adverse effects of antimicrobial chemotherapy[J]. Lancet Infect. Dis., 2004, 4(10): 611-619.
[44] Marchant J. When antibiotics turn toxic[J]. Nature, 2018, 555(7697): 431-433.
[45] Antonopoulos D A, Huse S M, Morrison H G, et al.. Reproducible community dynamics of the gastrointestinal microbiota following antibiotic perturbation[J]. Infect. Immun., 2009, 77(6): 2367-2375.
[46] Boutin R C T, Dwyer Z, Farmer K, et al.. Perinatal antibiotic exposure alters composition of murine gut microbiota and may influence later responses to peanut antigen[J]. Allergy Asthma Clin. Immunol., 2018, 14(1): 42.
[47] Haak B W, Lankelma J M, Hugenholtz F, et al.. Long-term impact of oral vancomycin, ciprofloxacin and metronidazole on the gut microbiota in healthy humans[J]. J. Antimicrob. Chemoth., 2018, 74(3): 782-786.
[48] Scott N A, Andrusaite A, Andersen P, et al.. Antibiotics induce sustained dysregulation of intestinal T cell immunity by perturbing macrophage homeostasis[J]. Sci. Transl. Med., 2018, 10(464): 47-55.
[49] Ley R E, Turnbaugh P J, Klein S, et al.. Microbial ecology: Human gut microbes associated with obesity[J]. Nature, 2006, 444(7122): 1022-1023.
[50] De L C M F, Durand T, Lalande V, et al.. Effect of antibiotic therapy on human fecal microbiota and the relation to the development of clostridium difficile[J]. Microb. Ecol., 2008, 56(3): 395-402.
[51] Sansonetti P J, Di Santo J P. Debugging how bacteria manipulate the immune response[J]. Immunity, 2007, 26(2): 149-161.
[52] Stark C M, Susi A, Emerick J, et al.. Antibiotic and acid-suppression medications during early childhood are associated with obesity[J]. Gut, 2019, 68(1): 62-69.
[53] Golkar Z, Bagasra O, Pace D G. Bacteriophage therapy: A potential solution for the antibiotic resistance crisis[J]. J. Infect. Dev. Countr., 2014, 8(2): 129-136.
[54] Barlow G. Clinical challenges in antimicrobial resistance[J]. Nat. Microbiol., 2018, 3(3): 258.
[55] Spellberg B, Gilbert D N. The future of antibiotics and resistance: A tribute to a career of leadership by John Bartlett[J]. Clin. Infect. Dis., 2014, 59(suppl_2): S71-S75.
[56] Michael C A, Dominey H D, Labbate M. The antimicrobial resistance crisis: Causes, consequences, and management[J]. Front. Public Health, 2014, 2: 145.
[57] Hu J, Ma L, Nie Y, et al.. A microbiota-derived bacteriocin targets the host to confer diarrhea resistance in early-weaned piglets[J]. Cell Host Microbe, 2018, 24(6): 817-832.
[58] Huang P, Zhang Y, Xiao K, et al.. The chicken gut metagenome and the modulatory effects of plant-derived benzylisoquinoline alkaloids[J]. Microbiome, 2018, 6(1): 211.
[2] Lienert J, Gudel K, Escher B I. Screening method for ecotoxicological hazard assessment of 42 pharmaceuticals considering human metabolism and excretory routes[J]. Environ. Sci. Technol., 2007, 41(12): 4471-4478.
[3] Sarmaha A K, Meyer M T, Boxallo A B A. A Global perspective on the use, sales, exposure pathways, occurrence, fate and effects of veterinary antibiotics (VAs) in the environment[J]. Chemosphere, 2006, 65(5): 725-759.
[4] Hirsch R, Ternes T, Haberer K, et al.. Occurrence of antibiotics in the aquatic environment[J]. Sci. Total Environ., 1999, 225(1): 109-118.
[5] Hu X, Zhou Q, Luo Y. Occurrence and source analysis of typical veterinary antibiotics in manure, soil, vegetables and groundwater from organic vegetable bases, Northern China[J]. Environ. Pollut., 2010, 158(9): 2992-2998.
[6] Selvam A, Xu D, Zhao Z, et al.. Fate of tetracycline, sulfonamide and fluoroquinolone resistance genes and the changes in bacterial diversity during composting of swine manure[J]. Bioresource Technol., 2012, 126: 383-390.
[7] Colomer-Lluch M, Imamovic L, Jofre J, et al.. Bacteriophages carrying antibiotic resistance genes in fecal waste from cattle, pigs, and poultry[J]. Antimicrob. Agents Chemoth., 2011, 55(10): 4908-4911.
[8] Ji X, Shen Q, Liu F, et al.. Antibiotic resistance gene abundances associated with antibiotics and heavy metals in animal manures and agricultural soils adjacent to feedlots in Shanghai China[J]. J. Hazard. Mater., 2012, 235: 178-185.
[9] Ma L, Xia Y, Li B, et al.. Metagenomic assembly reveals hosts of antibiotic resistance genes and the shared resistome in pig, chicken, and human feces[J]. Environ. Sci. Technol., 2015, 50(1): 420-427.
[10] Luo Y, Mao D, Rysz M, et al.. Trends in antibiotic resistance genes occurrence in the Haihe River, China[J]. Environ. Sci. Technol., 2010, 44(19): 7220-7225.
[11] Su H C, Ying G G, Tao R, et al.. Class 1 and 2 integrons, sul resistance genes and antibiotic resistance in Escherichia coli isolated from Dongjiang River, South China[J]. Environ. Pollut., 2012, 169: 42-49.
[12] Phillips I, Casewell M, Cox T, et al.. Does the use of antibiotics in food animals pose a risk to human health? A critical review of published data[J]. J. Antimicrob. Chemoth., 2004, 53(1): 28-52.
[13] Miller G Y, Algozin K A, Mcnamara P E, et al.. Productivity and economic effects of antibiotics used for growth promotion in US pork production[J]. J. Agric. Appl. Econ., 2003, 35(3): 469-482.
[14] 贺德春, 许振成, 吴根义, 等. 四环素类抗生素的环境行为研究进展[J]. 动物医学进展, 2011, 32(4):98-102.
[15] Zhao L, Dong Y H, Wang H. Residues of veterinary antibiotics in manures from feedlot livestock in eight provinces of China[J]. Sci. Total Environ., 2010, 408(5): 1069-1075.
[16] Hu X G, Luo Y, Zhou Q X, et al.. Determination of thirteen antibiotics residues in manure by solid phase extraction and high performance liquid chromatography[J]. Chin. J. Anal. Chem., 2008, 36(9): 1162-1166.
[17] Qiao M, Chen W, Su J, et al.. Fate of tetracyclines in swine manure of three selected swine farms in China[J]. J. Environ. Sci. China, 2012, 24(6): 1047-1052.
[18] Hou J, Wan W, Mao D, et al.. Occurrence and distribution of sulfonamides, tetracyclines, quinolones, macrolides, and nitrofurans in livestock manure and amended soils of Northern China[J]. Environ. Sci. Pollut. R., 2015, 22(6): 4545-4554.
[19] Wang N, Guo X, Xu J, et al.. Pollution characteristics and environmental risk assessment of typical veterinary antibiotics in livestock farms in Southeastern China[J]. J. Environ. Sci. Health B, 2014, 49(7): 468-479.
[20] Zhang H, Luo Y, Wu L, et al.. Residues and potential ecological risks of veterinary antibiotics in manures and composts associated with protected vegetable farming[J]. Environ. Sci. Pollut. R., 2015, 22(8): 5908-5918.
[21] Li Y, Zhang X, Li W, et al.. The residues and environmental risks of multiple veterinary antibiotics in animal faeces[J]. Environ. Monit. Assess., 2013, 185(3): 2211-2220.
[22] He L Y, Ying G G, Liu Y S, et al.. Discharge of swine wastes risks water quality and food safety: Antibiotics and antibiotic resistance genes from swine sources to the receiving environments[J]. Environ. Int., 2016, 92: 210-219.
[23] 广东省统计局. 2018年广东统计年鉴[M]. 北京: 中国统计出版社, 2018.
[24] Xu W, Zhang G, Zou S, et al.. Determination of selected antibiotics in the Victoria Harbour and the Pearl River, South China using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry[J]. Environ. Pollut., 2007, 145(3): 672-679.
[25] Wei R, Ge F, Huang S, et al.. Occurrence of veterinary antibiotics in animal wastewater and surface water around farms in Jiangsu Province, China[J]. Chemosphere, 2011, 82(10): 1408-1414.
[26] Xu W, Zhang G, Zou S, et al.. A preliminary investigation on the occurrence and distribution of antibiotics in the Yellow River and its tributaries, China[J]. Water Environ. Res., 2009, 81(3): 248-254.
[27] Li W, Shi Y, Gao L, et al.. Occurrence of antibiotics in water, sediments, aquatic plants, and animals from Baiyangdian Lake in North China[J]. Chemosphere, 2012, 89(11): 1307-1315.
[28] Tao R, Ying G G, Su H C, et al.. Detection of antibiotic resistance and tetracycline resistance genes in enterobacteriaceae isolated from the Pearl Rivers in South China[J]. Environ. Pollut., 2010, 158(6): 2101-2109.
[29] Jiang L, Hu X, Xu T, et al.. Prevalence of antibiotic resistance genes and their relationship with antibiotics in the Huangpu River and the drinking water sources, Shanghai, China[J]. Sci. Total Environ., 2013, 458: 267-272.
[30] Zhou L J, Ying G G, Zhao J L, et al.. Trends in the occurrence of human and veterinary antibiotics in the sediments of the Yellow River, Hai River and Liao River in Northern China[J]. Environ. Pollut., 2011, 159(7): 1877-1885.
[31] Davies J. Origins and evolution of antibiotic resistance[J]. Microbiol. Mol. Biol. Rev., 1996, 12(1): 9-16.
[32] Wright G D. The antibiotic resistome: The nexus of chemical and genetic diversity[J]. Nat. Rev. Microbiol., 2007, 5(3): 175-186.
[33] Kruse H, S?rum H. Transfer of multiple drug resistance plasmids between bacteria of diverse origins in natural microenvironments[J]. Appl. Environ. Microbiol., 1994, 60(11): 4015-4021.
[34] Gillings M R, Stokes H W. Are humans increasing bacterial evolvability?[J]. Trends Ecol. Evol., 2012, 27(6): 346-352.
[35] Heuer H, Schmitt H, Smalla K. Antibiotic resistance gene spread due to manure application on agricultural fields[J]. Curr. Opin. Microbiol., 2011, 14(3): 236-243.
[36] Conde C M, álvarez E C, Paradelo N R, et al.. Occurrence of tetracyclines and sulfonamides in manures, agricultural soils and crops from different areas in Galicia (NW Spain) [J]. J. Clean. Prod., 2018, 197: 491-500.
[37] Zhao F, Yang L, Chen L, et al.. Bioaccumulation of antibiotics in crops under long-term manure application: Occurrence, biomass response and human exposure[J]. Chemosphere, 2019, 219: 882-895.
[38] 刘晓瑜, 马玉超. 抗耐药细菌药用植物内生菌的筛选与鉴定[J]. 生物技术通报, 2015, 31(3):154-160.
[39] Wang F H, Qiao M, Chen Z, et al.. Antibiotic resistance genes in manure-amended soil and vegetables at harvest[J]. J. Hazard. Mater., 2015, 299: 215-221.
[40] Yang Q, Ren S, Niu T, et al.. Distribution of antibiotic-resistant bacteria in chicken manure and manure-fertilized vegetables[J]. Environ. Sci. Pollut. Res., 2014, 21(2): 1231-1241.
[41] Marti R, Scott A, Tien Y C, et al.. Impact of manure fertilization on the abundance of antibiotic-resistant bacteria and frequency of detection of antibiotic resistance genes in soil and on vegetables at harvest[J]. Appl. Environ. Microbiol., 2013, 79(18): 5701-5709.
[42] Kuppusamy S, Kakarla D, Venkateswarlu K, et al.. Veterinary antibiotics (VAs) contamination as a global agro-ecological issue: A critical view[J]. Agric. Ecosyst. Environ., 2018, 257: 47-59.
[43] Dancer S J. How Antibiotics can make us sick: The less obvious adverse effects of antimicrobial chemotherapy[J]. Lancet Infect. Dis., 2004, 4(10): 611-619.
[44] Marchant J. When antibiotics turn toxic[J]. Nature, 2018, 555(7697): 431-433.
[45] Antonopoulos D A, Huse S M, Morrison H G, et al.. Reproducible community dynamics of the gastrointestinal microbiota following antibiotic perturbation[J]. Infect. Immun., 2009, 77(6): 2367-2375.
[46] Boutin R C T, Dwyer Z, Farmer K, et al.. Perinatal antibiotic exposure alters composition of murine gut microbiota and may influence later responses to peanut antigen[J]. Allergy Asthma Clin. Immunol., 2018, 14(1): 42.
[47] Haak B W, Lankelma J M, Hugenholtz F, et al.. Long-term impact of oral vancomycin, ciprofloxacin and metronidazole on the gut microbiota in healthy humans[J]. J. Antimicrob. Chemoth., 2018, 74(3): 782-786.
[48] Scott N A, Andrusaite A, Andersen P, et al.. Antibiotics induce sustained dysregulation of intestinal T cell immunity by perturbing macrophage homeostasis[J]. Sci. Transl. Med., 2018, 10(464): 47-55.
[49] Ley R E, Turnbaugh P J, Klein S, et al.. Microbial ecology: Human gut microbes associated with obesity[J]. Nature, 2006, 444(7122): 1022-1023.
[50] De L C M F, Durand T, Lalande V, et al.. Effect of antibiotic therapy on human fecal microbiota and the relation to the development of clostridium difficile[J]. Microb. Ecol., 2008, 56(3): 395-402.
[51] Sansonetti P J, Di Santo J P. Debugging how bacteria manipulate the immune response[J]. Immunity, 2007, 26(2): 149-161.
[52] Stark C M, Susi A, Emerick J, et al.. Antibiotic and acid-suppression medications during early childhood are associated with obesity[J]. Gut, 2019, 68(1): 62-69.
[53] Golkar Z, Bagasra O, Pace D G. Bacteriophage therapy: A potential solution for the antibiotic resistance crisis[J]. J. Infect. Dev. Countr., 2014, 8(2): 129-136.
[54] Barlow G. Clinical challenges in antimicrobial resistance[J]. Nat. Microbiol., 2018, 3(3): 258.
[55] Spellberg B, Gilbert D N. The future of antibiotics and resistance: A tribute to a career of leadership by John Bartlett[J]. Clin. Infect. Dis., 2014, 59(suppl_2): S71-S75.
[56] Michael C A, Dominey H D, Labbate M. The antimicrobial resistance crisis: Causes, consequences, and management[J]. Front. Public Health, 2014, 2: 145.
[57] Hu J, Ma L, Nie Y, et al.. A microbiota-derived bacteriocin targets the host to confer diarrhea resistance in early-weaned piglets[J]. Cell Host Microbe, 2018, 24(6): 817-832.
[58] Huang P, Zhang Y, Xiao K, et al.. The chicken gut metagenome and the modulatory effects of plant-derived benzylisoquinoline alkaloids[J]. Microbiome, 2018, 6(1): 211.