Article(id=1307013521720496249, tenantId=1146029695717560320, journalId=1306274286668972124, issueId=1307013423896753139, articleNumber=null, orderNo=null, doi=10.11843/j.issn.0366-6964.2026.03.014, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1753891200000, receivedDateStr=2025-07-31, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1789545906715, onlineDateStr=2026-09-16, pubDate=1774195200000, pubDateStr=2026-03-23, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1789545906715, onlineIssueDateStr=2026-09-16, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1789545906715, creator=13701087609, updateTime=1789545906715, updator=13701087609, issue=Issue{id=1307013423896753139, tenantId=1146029695717560320, journalId=1306274286668972124, year='2026', volume='57', issue='3', pageStart='1177', pageEnd='1776', issueExtLink='null', onlineDate='null', pubDate='1774195200000', pubDateStr='2026-03-23', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=null, createTime=1789545883392, creator='13701087609', updateTime=1789609930841, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1307282058464743901, tenantId=1146029695717560320, journalId=1306274286668972124, issueId=1307013423896753139, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1307282058464743902, tenantId=1146029695717560320, journalId=1306274286668972124, issueId=1307013423896753139, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=1324, endPage=1333, ext={EN=ArticleExt(id=1307013521951182970, articleId=1307013521720496249, tenantId=1146029695717560320, journalId=1306274286668972124, language=EN, title=Research Progress on Bacteriophage Applications for Single-Dose Prevention and Control of Salmonella Infection in the Poultry Production Chain, columnId=1307007397399126026, journalTitle=Acta Veterinaria et Zootechnica Sinica, columnName=REVIEW, runingTitle=null, highlight=null, articleAbstract=

Salmonella poses a significant threat as a foodborne pathogen impacting global public health and the poultry industry. The escalating challenge of antibiotic resistance has intensified the difficulties in its control and prevention. Bacteriophage (phage) therapy, characterized by its high host specificity and intrinsic self-replication capability, has emerged as a promising novel biocontrol strategy to replace or complement antibiotics. Currently, several phage-based products targeting Salmonella are commercially deployed in livestock farming and poultry product processing. Extensive research and field trials have demonstrated their efficacy in reducing Salmonella loads within live poultry, decreasing mortality rates, enhancing production performance, and significantly reducing Salmonella contamination on poultry meat and eggs. Despite the promising potential, further field trials within commercial farm environments and robust clinical studies are imperative to evaluate clinical efficacy comprehensively, optimize application protocols, and promote standardized implementation.

, authors=Yuanhang ZHAO, Shenyu PANG, Jun SONG, Jiasan ZHENG, Dongyang GAO, authorsList=Yuanhang ZHAO, Shenyu PANG, Jun SONG, Jiasan ZHENG, Dongyang GAO, authorCompany=null, correspAuthors=Jiasan ZHENG, Dongyang GAO, authorNote=null, correspAuthorsNote=
GAO Dongyang, E-mail:
ZHENG Jiasan, E-mail:
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沙门菌是危害全球公共卫生及家禽养殖业的重要食源性病原体,抗生素耐药性问题加剧使其防控面临严峻挑战。噬菌体疗法凭借高度宿主特异性和自我扩增能力等优势,成为替代抗生素的新型生物防控策略。目前,多款靶向沙门菌的噬菌体产品已应用于家禽养殖环节及禽产品加工链。大量研究及田间试验证实,噬菌体能有效降低家禽体内沙门菌载量、减少死亡率并改善生产性能,同时在禽肉、禽蛋等产品上可显著减少沙门菌污染。尽管前景广阔,噬菌体疗法仍需更多规模化养殖环境下的田间试验和临床研究,以系统评估其临床效力、优化应用方案并推动规范化使用。

, authors=赵远航, 庞申雨, 宋军, 郑家三, 高东阳, authorsList=赵远航, 庞申雨, 宋军, 郑家三, 高东阳, authorCompany=null, correspAuthors=郑家三, 高东阳, authorNote=

赵远航,硕士生,主要从事动物疾病防控研究,E-mail:

, correspAuthorsNote=
高东阳,主要从事动物传染病诊断与防治研究,E-mail:
郑家三,主要从事奶牛肢蹄病病因学与综合防控研究,E-mail:
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DOI:10.1016/j.micpath.2025.107619, articleTitle=null, refAbstract=null), Reference(id=1307281640347164965, tenantId=1146029695717560320, journalId=1306274286668972124, articleId=1307013521720496249, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[62], rfOrder=65, authorNames=null, journalName=null, refType=null, unstructuredReference=GUO P,ZHANG L,NING M,et al.Characterization and release of casein‑sodium alginate embedding phage edible film and the application in controlling of Salmonella contamination in food[J].Int J Food Microbiol,2025,434:111137. DOI:10.1016/j.ijfoodmicro.2025.111137, articleTitle=null, refAbstract=null)], funds=[Fund(id=1307281633678221535, tenantId=1146029695717560320, journalId=1306274286668972124, articleId=1307013521720496249, awardId=2024MD763976, language=CN, fundingSource=中国博士后科学基金面上资助项目(2024MD763976), fundOrder=null, country=null), Fund(id=1307281633896325344, tenantId=1146029695717560320, journalId=1306274286668972124, articleId=1307013521720496249, awardId=LBH-Z24246, language=CN, fundingSource=黑龙江省博士后面上资助项目(LBH-Z24246), fundOrder=null, country=null), Fund(id=1307281633984405729, tenantId=1146029695717560320, journalId=1306274286668972124, articleId=1307013521720496249, awardId=QC2025C037, language=CN, fundingSource=黑龙江省自然科学基金资助项目(QC2025C037), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1307281628175294641, tenantId=1146029695717560320, journalId=1306274286668972124, articleId=1307013521720496249, xref=null, ext=[AuthorCompanyExt(id=1307281628183683250, tenantId=1146029695717560320, journalId=1306274286668972124, articleId=1307013521720496249, companyId=1307281628175294641, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Heilongjiang Bayi Agricultural University,Daqing 163319,China), AuthorCompanyExt(id=1307281628192071859, tenantId=1146029695717560320, journalId=1306274286668972124, articleId=1307013521720496249, companyId=1307281628175294641, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=黑龙江八一农垦大学,大庆 163319)])], figs=[ArticleFig(id=1307281632747086041, tenantId=1146029695717560320, journalId=1306274286668972124, articleId=1307013521720496249, language=EN, label=Fig.1, caption=Applications of bacteriophages in various scenarios (color images are provided in supplementary materials of OSID), figureFileSmall=RwaABiQU9kNpPpWpUyQzEA==, figureFileBig=B6Aei2Cp/TQ1AmWfvS66gg==, tableContent=null), ArticleFig(id=1307281632810000602, tenantId=1146029695717560320, journalId=1306274286668972124, articleId=1307013521720496249, language=CN, label=图1, caption=噬菌体在不同场景中的应用(彩图在OSID相关材料中提供), figureFileSmall=RwaABiQU9kNpPpWpUyQzEA==, figureFileBig=B6Aei2Cp/TQ1AmWfvS66gg==, tableContent=null), ArticleFig(id=1307281633074241755, tenantId=1146029695717560320, journalId=1306274286668972124, articleId=1307013521720496249, language=EN, label=Table 1, caption=

Application of Salmonella phages in poultry farming

, figureFileSmall=null, figureFileBig=null, tableContent=

动物

Animal

沙门菌血清型

Salmonella serotype

噬菌体

Phage

效果

Effect

文献Literature

雏鸡

(10日龄)

Chick

(10-day-old)

肠炎沙门菌混合噬菌体(BP1,BP2,BP3)与对照组(100%)相比,雾化吸入噬菌体可显著降低鸡感染沙门菌的发生率(72.7%)。此外,通过喷雾和饮用水口服噬菌体均降低了肠道内沙门菌的定植(P<0.01;P<0.05)[39]

蛋鸡

(6周龄)

Layer (6-week-old)

鸡伤寒沙门菌ST4,L13,SG3每个噬菌体以饲料添加剂的形式口服,噬菌体可以显著降低肝脏、脾脏和盲肠中的沙门菌分离率和死亡率[40]

雏鸡

(36日龄)

Chick

(36-day-old)

肠炎沙门菌P125109和鼠伤寒沙门菌4/74

混合噬菌体(φ151,

φ25,φ10)

单剂量口服1011 PFU噬菌体后,肠炎沙门菌和鼠伤寒沙门菌分别减少了1.53和3.48 lg CUF·g-1[41]

雏鸡

(1日龄)

Chick

(1-day-old)

肠炎沙门菌PT4混合噬菌体(CNPSA1,CNPSA3,CNPSA4)在6~10日龄(早期感染)和31~35日龄(后期感染)分别接受噬菌体治疗,肠道载菌量显著减少,后期治疗效果更好,平均减少1.08 lg CFU·g-1[42]

蛋鸡

(40周龄)

Layer (40-week-old)

肠炎沙门菌噬菌体混合物(SP-1,STP-1)在感染后第7 天,饲料中添加噬菌体组盲肠、肝脏和脾脏的减少量分别为0.9、0.57和0.38 lg CFU·g-1;在第6天,盲肠的减少量为0.86 lg CFU·g-1[43]

蛋鸡

(60周龄)

Layer (60-week-old)

自然感染肠炎沙门菌噬菌体AP(从分离病原体的同一环境中分离出的噬菌体)噬菌体在两个不同的时间应用(间隔24 h),第二次应用后下降幅度最大(1.78 lg CFU·g-1)[44]

SPF雏鸡

(1日龄)

SPF chick(1-day-old)

多重耐药肯塔基沙门菌噬菌体混合物噬菌体混合物能够阻止肯塔基沙门菌在盲肠中的定植,并将浓度从105 CFU·g-1降低到102 CFU·g-1[45]

肉鸡

(1日龄)

Broiler(1-day-old)

鼠伤寒沙门菌SL1344噬菌体混合物(SPFM10,SPFM14)在饲料中添加不同剂量的噬菌体鸡尾酒,可以有效减少沙门菌在鸡体内的定植,与没有噬菌体处理的感染组相比,体重也有所增加。[46]

肉鸡

(1日龄)

Broiler(1-day-old)

肠炎沙门菌、哈达尔沙门菌、婴儿沙门菌、鼠伤寒沙门菌、维尔肖沙门菌噬菌体混合物(vB_SenS_KP001,vB_SenS_KP005,vB_SenS_WP110)噬菌体可以减少肠道中沙门菌的定植,对肉仔鸡的生长和健康有一定的直接和间接影响。在商业肉鸡养殖场实际应用中也验证了噬菌体有效性[47]
), ArticleFig(id=1307281633153933532, tenantId=1146029695717560320, journalId=1306274286668972124, articleId=1307013521720496249, language=CN, label=表1, caption=

沙门菌噬菌体在家禽养殖环节中的应用研究

, figureFileSmall=null, figureFileBig=null, tableContent=

动物

Animal

沙门菌血清型

Salmonella serotype

噬菌体

Phage

效果

Effect

文献Literature

雏鸡

(10日龄)

Chick

(10-day-old)

肠炎沙门菌混合噬菌体(BP1,BP2,BP3)与对照组(100%)相比,雾化吸入噬菌体可显著降低鸡感染沙门菌的发生率(72.7%)。此外,通过喷雾和饮用水口服噬菌体均降低了肠道内沙门菌的定植(P<0.01;P<0.05)[39]

蛋鸡

(6周龄)

Layer (6-week-old)

鸡伤寒沙门菌ST4,L13,SG3每个噬菌体以饲料添加剂的形式口服,噬菌体可以显著降低肝脏、脾脏和盲肠中的沙门菌分离率和死亡率[40]

雏鸡

(36日龄)

Chick

(36-day-old)

肠炎沙门菌P125109和鼠伤寒沙门菌4/74

混合噬菌体(φ151,

φ25,φ10)

单剂量口服1011 PFU噬菌体后,肠炎沙门菌和鼠伤寒沙门菌分别减少了1.53和3.48 lg CUF·g-1[41]

雏鸡

(1日龄)

Chick

(1-day-old)

肠炎沙门菌PT4混合噬菌体(CNPSA1,CNPSA3,CNPSA4)在6~10日龄(早期感染)和31~35日龄(后期感染)分别接受噬菌体治疗,肠道载菌量显著减少,后期治疗效果更好,平均减少1.08 lg CFU·g-1[42]

蛋鸡

(40周龄)

Layer (40-week-old)

肠炎沙门菌噬菌体混合物(SP-1,STP-1)在感染后第7 天,饲料中添加噬菌体组盲肠、肝脏和脾脏的减少量分别为0.9、0.57和0.38 lg CFU·g-1;在第6天,盲肠的减少量为0.86 lg CFU·g-1[43]

蛋鸡

(60周龄)

Layer (60-week-old)

自然感染肠炎沙门菌噬菌体AP(从分离病原体的同一环境中分离出的噬菌体)噬菌体在两个不同的时间应用(间隔24 h),第二次应用后下降幅度最大(1.78 lg CFU·g-1)[44]

SPF雏鸡

(1日龄)

SPF chick(1-day-old)

多重耐药肯塔基沙门菌噬菌体混合物噬菌体混合物能够阻止肯塔基沙门菌在盲肠中的定植,并将浓度从105 CFU·g-1降低到102 CFU·g-1[45]

肉鸡

(1日龄)

Broiler(1-day-old)

鼠伤寒沙门菌SL1344噬菌体混合物(SPFM10,SPFM14)在饲料中添加不同剂量的噬菌体鸡尾酒,可以有效减少沙门菌在鸡体内的定植,与没有噬菌体处理的感染组相比,体重也有所增加。[46]

肉鸡

(1日龄)

Broiler(1-day-old)

肠炎沙门菌、哈达尔沙门菌、婴儿沙门菌、鼠伤寒沙门菌、维尔肖沙门菌噬菌体混合物(vB_SenS_KP001,vB_SenS_KP005,vB_SenS_WP110)噬菌体可以减少肠道中沙门菌的定植,对肉仔鸡的生长和健康有一定的直接和间接影响。在商业肉鸡养殖场实际应用中也验证了噬菌体有效性[47]
), ArticleFig(id=1307281633216848093, tenantId=1146029695717560320, journalId=1306274286668972124, articleId=1307013521720496249, language=EN, label=Table 2, caption=

Application of Salmonella phages in poultry products processing

, figureFileSmall=null, figureFileBig=null, tableContent=

食品

Food

沙门菌血清型Salmonella serotype噬菌体Phage效果Effect文献Literature

禽肉

Poultry

混合沙门菌

噬菌体S16和

FelixO1a(FO1a)

经噬菌体处理30 min后,鸡肉中沙门菌载量显著降低1.1 lg CFU·g-1(P<0.05);处理6 h后,鸡肉污染水平下降0.9 lg CFU·g-1(P<0.01)[54]

新鲜鸡蛋和鸡肉

Fresh eggs and chicken

肠炎沙门菌SE07经噬菌体处理48 h(4 ℃),新鲜鸡蛋与鸡肉中肠炎沙门菌载量显著降低2.0 lg CFU·mL-1或lg CFU·g-1[55]

鸡胸肉

Chicken breast

混合肠炎沙门菌噬菌体混合物(PA13076和PC2184)经噬菌体处理5 h(4 ℃),鸡胸肉沙门菌载量较初始值显著降低2.5 lg CFU·样品-1[56]

鸡胸肉

Chicken breast

鼠伤寒沙门菌、肠炎沙门菌、海德堡沙门菌

SalmoFresh TM

(6 phages)

在4 ℃条件下处理鸡胸肉,第0、1和7天,沙门菌计数分别减少1.2、1.1和1.2 lg CFU·g-1;在室温条件下,在0、4和8 h,沙门菌计数依次降低0.8、0.9和0.4 lg CFU·g-1[57]

鸡肉

Chicken

肠炎沙门菌

PhageGuard S®

(2 phages)

无论是在人工模拟污染场景下对沙门菌的靶向抑制,还是在工厂规模化生产中对家禽产品的实际处理,噬菌体均展现出稳定且高效的杀菌能力,为家禽产品的微生物安全控制提供了可靠的技术支持[58]

鸡胸肉和带壳蛋

Chicken breast and in-shell egg

肠炎沙门菌混合噬菌体€P54、€P59、€P66和€P72噬菌体处理能显著抑制鸡胸肉和带壳蛋上的细菌载量,且在4 ℃低温环境下抑菌效果更优。[59]
带壳鸡蛋和鸡肉In-shell eggs and chicken肠炎沙门菌噬菌体sp11241和8-19噬菌体SP11241和8-1在MOI为100时,分别于3 h和6 h实现蛋壳表面沙门菌的完全清除,且随着MOI值升高,清除时间进一步缩短。其中,SP11241处理生鸡肉12 h后,可使沙门菌数量最大降低3.17 lg CFU·mL-1,展现出显著的靶向抑菌效果[60]

鸡肉

Chicken

肠炎沙门菌噬菌体S3和2-3在MOI为10 000的条件下,噬菌体2~3处理鸡肉样品12 h后,沙门菌数量最大降幅达1.15 lg CFU/mL,与初始菌量相比抑菌率显著超过92%,展现出噬菌体在高感染复数下对禽肉中沙门菌的高效抑制作用[61]

鸡胸肉

Chicken breast

肠炎沙门菌噬菌体SaTp-04采用酪蛋白与海藻酸钠对噬菌体SaTp-04进行包埋处理后应用于鸡胸肉,结果显示其表面沙门菌数量较对照组降低约6 lg CFU·cm-²,该微胶囊化技术通过提升噬菌体在食品基质中的稳定性,实现了对禽肉表面致病菌的高效抑制,为噬菌体在即食肉类保鲜中的应用提供了新的技术路径[62]
), ArticleFig(id=1307281633481089246, tenantId=1146029695717560320, journalId=1306274286668972124, articleId=1307013521720496249, language=CN, label=表2, caption=

沙门菌噬菌体在家禽产品加工环节中的应用研究

, figureFileSmall=null, figureFileBig=null, tableContent=

食品

Food

沙门菌血清型Salmonella serotype噬菌体Phage效果Effect文献Literature

禽肉

Poultry

混合沙门菌

噬菌体S16和

FelixO1a(FO1a)

经噬菌体处理30 min后,鸡肉中沙门菌载量显著降低1.1 lg CFU·g-1(P<0.05);处理6 h后,鸡肉污染水平下降0.9 lg CFU·g-1(P<0.01)[54]

新鲜鸡蛋和鸡肉

Fresh eggs and chicken

肠炎沙门菌SE07经噬菌体处理48 h(4 ℃),新鲜鸡蛋与鸡肉中肠炎沙门菌载量显著降低2.0 lg CFU·mL-1或lg CFU·g-1[55]

鸡胸肉

Chicken breast

混合肠炎沙门菌噬菌体混合物(PA13076和PC2184)经噬菌体处理5 h(4 ℃),鸡胸肉沙门菌载量较初始值显著降低2.5 lg CFU·样品-1[56]

鸡胸肉

Chicken breast

鼠伤寒沙门菌、肠炎沙门菌、海德堡沙门菌

SalmoFresh TM

(6 phages)

在4 ℃条件下处理鸡胸肉,第0、1和7天,沙门菌计数分别减少1.2、1.1和1.2 lg CFU·g-1;在室温条件下,在0、4和8 h,沙门菌计数依次降低0.8、0.9和0.4 lg CFU·g-1[57]

鸡肉

Chicken

肠炎沙门菌

PhageGuard S®

(2 phages)

无论是在人工模拟污染场景下对沙门菌的靶向抑制,还是在工厂规模化生产中对家禽产品的实际处理,噬菌体均展现出稳定且高效的杀菌能力,为家禽产品的微生物安全控制提供了可靠的技术支持[58]

鸡胸肉和带壳蛋

Chicken breast and in-shell egg

肠炎沙门菌混合噬菌体€P54、€P59、€P66和€P72噬菌体处理能显著抑制鸡胸肉和带壳蛋上的细菌载量,且在4 ℃低温环境下抑菌效果更优。[59]
带壳鸡蛋和鸡肉In-shell eggs and chicken肠炎沙门菌噬菌体sp11241和8-19噬菌体SP11241和8-1在MOI为100时,分别于3 h和6 h实现蛋壳表面沙门菌的完全清除,且随着MOI值升高,清除时间进一步缩短。其中,SP11241处理生鸡肉12 h后,可使沙门菌数量最大降低3.17 lg CFU·mL-1,展现出显著的靶向抑菌效果[60]

鸡肉

Chicken

肠炎沙门菌噬菌体S3和2-3在MOI为10 000的条件下,噬菌体2~3处理鸡肉样品12 h后,沙门菌数量最大降幅达1.15 lg CFU/mL,与初始菌量相比抑菌率显著超过92%,展现出噬菌体在高感染复数下对禽肉中沙门菌的高效抑制作用[61]

鸡胸肉

Chicken breast

肠炎沙门菌噬菌体SaTp-04采用酪蛋白与海藻酸钠对噬菌体SaTp-04进行包埋处理后应用于鸡胸肉,结果显示其表面沙门菌数量较对照组降低约6 lg CFU·cm-²,该微胶囊化技术通过提升噬菌体在食品基质中的稳定性,实现了对禽肉表面致病菌的高效抑制,为噬菌体在即食肉类保鲜中的应用提供了新的技术路径[62]
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噬菌体在家禽产业链中单次防治沙门菌感染的应用研究进展
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赵远航 , 庞申雨 , 宋军 , 郑家三 , 高东阳
畜牧兽医学报 | 综述 2026,57(3): 1324-1333
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畜牧兽医学报 |综述 2026 , 57 (3) : 1324 -1333
噬菌体在家禽产业链中单次防治沙门菌感染的应用研究进展
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赵远航 , 庞申雨, 宋军, 郑家三 , 高东阳
作者信息
  • 黑龙江八一农垦大学,大庆 163319
通讯作者:
高东阳,主要从事动物传染病诊断与防治研究,E-mail:
郑家三,主要从事奶牛肢蹄病病因学与综合防控研究,E-mail:
作者简介:

赵远航,硕士生,主要从事动物疾病防控研究,E-mail:

Research Progress on Bacteriophage Applications for Single-Dose Prevention and Control of Salmonella Infection in the Poultry Production Chain
Yuanhang ZHAO , Shenyu PANG, Jun SONG, Jiasan ZHENG , Dongyang GAO
Affiliations
  • Heilongjiang Bayi Agricultural University,Daqing 163319,China
  • Corresponding Author:
    GAO Dongyang, E-mail:
    ZHENG Jiasan, E-mail:
出版时间: 2026-03-23 doi: 10.11843/j.issn.0366-6964.2026.03.014
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沙门菌是危害全球公共卫生及家禽养殖业的重要食源性病原体,抗生素耐药性问题加剧使其防控面临严峻挑战。噬菌体疗法凭借高度宿主特异性和自我扩增能力等优势,成为替代抗生素的新型生物防控策略。目前,多款靶向沙门菌的噬菌体产品已应用于家禽养殖环节及禽产品加工链。大量研究及田间试验证实,噬菌体能有效降低家禽体内沙门菌载量、减少死亡率并改善生产性能,同时在禽肉、禽蛋等产品上可显著减少沙门菌污染。尽管前景广阔,噬菌体疗法仍需更多规模化养殖环境下的田间试验和临床研究,以系统评估其临床效力、优化应用方案并推动规范化使用。

噬菌体  /  沙门菌  /  抗生素耐药  /  噬菌体疗法  /  家禽

Salmonella poses a significant threat as a foodborne pathogen impacting global public health and the poultry industry. The escalating challenge of antibiotic resistance has intensified the difficulties in its control and prevention. Bacteriophage (phage) therapy, characterized by its high host specificity and intrinsic self-replication capability, has emerged as a promising novel biocontrol strategy to replace or complement antibiotics. Currently, several phage-based products targeting Salmonella are commercially deployed in livestock farming and poultry product processing. Extensive research and field trials have demonstrated their efficacy in reducing Salmonella loads within live poultry, decreasing mortality rates, enhancing production performance, and significantly reducing Salmonella contamination on poultry meat and eggs. Despite the promising potential, further field trials within commercial farm environments and robust clinical studies are imperative to evaluate clinical efficacy comprehensively, optimize application protocols, and promote standardized implementation.

phage  /  Salmonella  /  antibiotic resistance  /  bacteriophage therapy  /  poultry
赵远航, 庞申雨, 宋军, 郑家三, 高东阳. 噬菌体在家禽产业链中单次防治沙门菌感染的应用研究进展. 畜牧兽医学报, 2026 , 57 (3) : 1324 -1333 . DOI: 10.11843/j.issn.0366-6964.2026.03.014
Yuanhang ZHAO, Shenyu PANG, Jun SONG, Jiasan ZHENG, Dongyang GAO. Research Progress on Bacteriophage Applications for Single-Dose Prevention and Control of Salmonella Infection in the Poultry Production Chain[J]. Acta Veterinaria et Zootechnica Sinica, 2026 , 57 (3) : 1324 -1333 . DOI: 10.11843/j.issn.0366-6964.2026.03.014
沙门菌(Salmonella)作为重要的人畜共患病原体,严重威胁养殖业发展和人类健康,是国内外细菌性食物中毒的主要诱因[1]。该菌可感染多种畜禽,且具备经种禽垂直传播的特性,导致养殖场一旦暴发便极难根除,严重制约养殖业可持续发展。伴随生活水平提升,畜禽产品需求持续增长,养殖规模扩大,沙门菌感染风险相应增加。然而,大量抗生素的使用导致耐药菌株甚至多药耐药(multidrug resistance,MDR)菌株的出现,给疾病的防控带来一定的困难和挑战,严重威胁着全球公共卫生[2]。因此,开发更加安全有效的抗生素替代产品用于沙门菌的防控显得尤为必要。近年来,噬菌体(phage)已被证实为有效的抗生素替代品,在控制动物和人类致病性细菌感染方面发挥重要作用。
沙门菌属(Salmonella spp.)是一类革兰阴性兼性厌氧杆菌,作为全球范围内胃肠炎的主要病原体,其引发的沙门菌病严重威胁公共卫生,并造成家禽养殖业重大经济损失[3⁃7]。该病原体可经由水平传播或垂直传播途径扩散,人类因摄入被污染的水源或食物(尤其是禽类制品)而感染,临床表现为突发性腹泻、发热、腹部绞痛及呕吐等症状[8]。据流行病学统计,全球每年约发生9 380万例人源沙门菌感染病例,致死人数达15.5万例[9];仅2017年全球就有53.5万例感染病例,造成全球7.75万人死亡[10]。家禽作为重要宿主,其慢性携带状态导致病原体在养殖链中持续扩散,形成“动物-环境-人类”的传播循环,显著加剧疾病防控难度。
沙门菌属包含肠道沙门菌(Salmonella enterica)和邦戈沙门菌(Salmonella bongori)两个种,其中肠道沙门菌肠道亚种(S. enterica subsp. enterica)是导致临床感染的主要类群,目前已鉴定出超过2 659种血清型[11]。具有重要公共卫生意义的血清型包括肠炎沙门菌(Salmonella Enteritidis)和鼠伤寒沙门菌(Salmonella Typhimurium),二者常引发人类食源性感染[12]。在家禽领域,鸡白痢沙门菌(Salmonella Pullorum)和鸡伤寒沙门菌(Salmonella Gallinarum)具有严格宿主特异性,可导致禽类败血症及高致死率的伤寒病症,对养禽业构成直接威胁。
沙门菌耐药性问题已构成全球公共卫生危机。自20世纪60年代首次报道氯霉素耐药株以来,其耐药谱系持续扩展,目前多药耐药性(MDR)已涵盖氨苄西林、氯霉素及甲氧苄啶-磺胺甲恶唑等一线药物[13]。为了控制抗生素耐药细菌的蔓延,许多欧洲国家的卫生当局很早就已经限制在家禽饲料中使用抗生素[14]。瑞典是第一个禁止将抗生素用于促进动物生长(1986年)和预防使用(1988年)的国家[15]。2011年,这些国家禁止使用所有基本的抗生素作为预防药物[16]。尽管有这些规定,但目前生产的所有抗生素中至少有60%被用于畜牧业生产[17-18]。中国自2020年7月1日起,饲料生产企业停止生产含促生长类药物饲料添加剂(中药类除外)的商品饲料;2022年发布的《遏制微生物耐药国家行动计划(2022—2025年)》进一步强调遏制微生物耐药工作的紧迫性与重要性。在此背景下,能够治疗细菌性感染的噬菌体凭借其高度宿主特异性和自我扩增能力等优势,成为替代抗生素的新兴研究焦点,有望为解决沙门菌耐药困境开辟新路径。
噬菌体(bacteriophage,phage)是地球上已知的种类最多样化和数量最多的微生物,数量可达到1031[19]。作为一种能够特异性感染细菌、古菌等原核生物的病毒,噬菌体由Frederick Twort和Félix d’Hérelle分别于1915年和1917年独立发现[20]。Félix d’Hérelle将他发现的可以拮抗痢疾杆菌的微生物命名为“噬菌体”,意思是“细菌吞噬者”,并率先提出了“噬菌体疗法”的概念。在抗生素尚未问世的年代,细菌性感染严重威胁人类生命,这一具有对抗细菌病原体潜力的微生物的发现备受瞩目,其深入研究前景也得到了众多学者的认可。然而,亚历山大-弗莱明在1928年发现了抗生素[21],极大地转移了研究重心,导致噬菌体疗法的探索一度被边缘化。近年来,随着抗生素耐药性问题在全球范围内日益严峻,“噬菌体疗法”这一概念正重新获得高度关注[22⁃23]。
噬菌体疗法展现出多项显著优势[24⁃28]:首先,其具备高度的宿主特异性,可精准靶向特定病原菌,最大限度保护共生微生物群落,避免了广谱抗生素常见的微生态失衡问题。其次,噬菌体具有自我扩增能力,能在感染部位利用宿主菌进行复制,局部浓度随病原菌存在而显著提升,从而增强抗菌效力。第三,噬菌体的发现与制备过程相对便捷且成本效益显著。第四,经筛选的烈性噬菌体本身对哺乳动物细胞无毒性,且因其高度特异性的裂解模式,临床安全性已获证实,通常仅引发轻微或可忽略的副作用。最后,噬菌体在完成治疗清除病原体后,可在组织中迅速清除,不产生残留,故在兽医学应用中无需设定休药期。
研究表明,在食用动物屠宰前或后施用噬菌体可有效抑制目标细菌生长,表明其作为食品生产链抗菌剂的潜力[29]。噬菌体可通过饲喂或直接喷洒应用于农场动物及作物,并适用于牛肉、水果、蔬菜及即食食品等产品的表面除菌(图1),同时能有效控制食品接触表面及加工设施中细菌病原体的交叉污染。农业与兽医学领域的噬菌体应用研究持续取得进展,2006年,美国农业部(USDA)与食品药品监督管理局(FDA)批准了全球首个食品添加剂用噬菌体制剂LMP-102TM,用于防控食品中的单核细胞增生李斯特菌污染[30]。针对沙门菌、大肠杆菌、金黄色葡萄球菌、产气荚膜梭菌等关键病原体(常引发人兽共患病或造成重大经济损失)的兽用噬菌体疗法研究已广泛开展。近年来,中国在噬菌体治疗的规范化与临床转化方面发展迅速,多项关键共识与标准相继出台,推动了噬菌体治疗的规范发展。2023年,《噬菌体治疗专家建议》和《预防及治疗用噬菌体质量标准专家共识》的发布为临床应用提供了初步指导[31];2024年,《临床治疗用噬菌体制剂质量要求》团体标准的出台,进一步对治疗用噬菌体产品的质量提出明确要求。同年,中国青岛诺安百特生物技术有限公司的沙门菌噬菌体产品获得美国FDA的GRAS(公认安全)认证[32],标志着我国在食源性致病菌噬菌体防控技术的突破;其自主研发的鸭大肠杆菌噬菌体制剂(ECP05株)更成功获得农业农村部临床试验批件,成为国内首个进入临床试验的兽用噬菌体制剂,是我国兽用噬菌体研发领域的里程碑事件。
噬菌体已被证实是治疗家禽细菌性疾病的可行策略。在家禽养殖业中,噬菌体治疗沙门菌有两个基本目的:其一,通过在养殖环节实施治疗,可最大程度减少沙门菌对动物健康和生产性能造成的损失;其二,基于噬菌体的生物防控是减少人类食源性沙门菌感染的有力工具。鉴于养殖环节是防控沙门菌沿产业链传播的关键源头,其成效直接关乎全链条食品安全,大量研究聚焦于噬菌体在家禽养殖中防控沙门菌的应用。
例如,Nabil等[33]评估了噬菌体疗法对感染肠炎沙门菌和鼠伤寒沙门菌雏鸡的效果:在雏鸡2日龄接种10⁵ CFU沙门菌后,从第1日龄起连续8次(第1、2、3、6、8、10、13、15日龄)饲喂10¹¹ PFU噬菌体。结果显示,感染后第3天雏鸡盲肠内沙门菌载量已开始下降,至第5天进一步减少,并从第7天起直至试验结束(第15天),所有雏鸡体内的两种沙门菌均被完全清除,证实了该疗法的有效性[33]。同样,Pourabadeh等[34]证明在肠炎沙门菌和鼠伤寒沙门菌污染的饲料中添加BP鸡尾酒,在7、14和21 d时显著降低了肉仔鸡肝脏、嗉囊、脾脏和盲肠中沙门菌的定植。多项类似研究结果(表1)一致证实,噬菌体凭借其精准裂解致病菌的特性,有望成为家禽沙门菌防控领域极具前景的新型生物防控工具。
目前,多种靶向沙门菌的噬菌体产品已在实践中应用。Biotector S1®(CJ CheilJedang Research Institute of Biotechnology, Seoul, South Korea)是一款特异性感染鸡伤寒沙门菌和鸡白痢沙门菌的噬菌体制剂。应用该产品可有效降低畜禽死亡率(73%~86%),提高蛋鸡产蛋率(约3%)及蛋重,并显著减少盲肠沙门菌载量(3~4 lg CUF·g-1),且未观察到器官损伤;田间试验证实其可将死亡率降低高达86%,展现出替代抗生素或与其协同增效防控耐药菌的潜力[35]。对SalmoFREE®(Theseo,Laval, France)在禽类生产系统中大规模应用的研究评估表明,该噬菌体产品安全性良好,能有效降低禽沙门菌发病率,且对鸡群行为及生产性能参数无显著负面影响,证实了其在生产规模下的有效性和安全性;养殖周期终点(第33天)检测显示,泄殖腔拭子中的沙门菌检出率降至0%[36]。另一款产品Bafasal®(Proteon Pharmaceuticals,Piotrkowska,Poland)作为禽类饲料添加剂,被证实安全有效,可将沙门菌载量显著降低,同时改善饲料转化率并降低死亡率[37⁃38]。
从生产到消费的整个畜禽产品食品链均易受有害微生物污染,食源性感染作为全球性重大公共卫生问题,虽在病原体监测方面取得进展,仍导致全球每年大量人群致病或死亡。传统食品抗菌方法(如巴氏杀菌、高压处理、辐照或化学消毒)虽能在不同程度上减少病原体,但存在显著局限:可能损坏设备、损害食品感官品质或营养价值;更重要的是,化学处理会同时杀灭有益于食品天然保存的微生物菌群。因此,开发噬菌体等高效天然替代品以控制食源性病原体更具优势。在食品工业中,噬菌体主要通过应用于初级生产、生物保存(biopreservation)和生物消毒(biosanitation)三个关键环节来保障食品安全。作为商业化抗菌制剂,噬菌体产品已用于清除动物源性食品(如肉类、乳制品)和植物源性食品(如新鲜果蔬)中的目标病原体。
在家禽食品安全领域,噬菌体生物防控技术凭借其特异性靶向优势,在“从农场到餐桌”全链条中展现出显著潜力。研究表明,噬菌体可有效减少禽肉制品中的沙门菌污染。例如,使用肠炎沙门菌人工污染无菌鸡块(5 cm×5 cm)后,应用浓度为10⁹ PFU·mL-1的噬菌体BF1354处理,并于4 ℃冷藏10 d。结果显示,在处理第1、6和10天,样品中的沙门菌数量分别较对照组显著减少2.1、2.0和0.8 lg CFU·g-1,证实其在冷藏条件下对鸡肉中沙门菌的有效控制[48]。另一项针对鸡皮的研究则评估了噬菌体LmqsSP1在低温环境下的除菌效果,当感染复数(multiplicity of infection,MOI)为10⁵时,处理3 h后沙门菌LT2及食源性分离株S1、S2的数量较对照组降低1.8 lg CFU·g-1;处理24 h后,分离株S1(P=0.021)和S2(P=0.032)的菌落数进一步减少2.2 lg CFU·g-1,LT2亦显著减少1.9 lg CFU·g-1(P=0.000 7)[49]。噬菌体的应用同样高效延伸至禽蛋,噬菌体vB_SenM_BP13076处理人工污染沙门菌的食用蛋,MOI为100时,24 h后在4和25 ℃下分别减少2.27和2.58 lg CFU·蛋-1;MOI为1 000时,在相同条件下分别减少2.58和2.60 lg CFU·蛋-1。处理污染种蛋12 h后(MOI=100和1 000),蛋表面菌负荷平均下降2.03和2.90 lg CFU·种蛋-1 [50]。多项类似研究(表2)共同证实了噬菌体在家禽产品加工链中防控沙门菌污染的有效性与应用价值。
沙门菌噬菌体在食品领域的商业化应用正稳步推进。2013年2月,Intralytix公司开发的噬菌体制剂Salmofresh™获得批准,用于控制家禽及其他食品中的沙门菌污染。此外,多款针对沙门菌的商业噬菌体产品正积极开发或应用,覆盖食品加工与动物健康领域:包括SalmoShield™(用于防控高致病性沙门菌对食品及加工设施的污染)、SalmoLyse™(专用于宠物食品沙门菌控制)、以及PhageGuard® S(可有效降低肉制品与家禽产品中的沙门菌污染水平)[51-52]。同时,Elanco动物保健公司与OmniLytics合作开发的Armament™噬菌体产品,旨在降低肉类和家禽在加工环节前的污染风险[53]。
抗生素的过度使用已引发全球性抗菌素耐药性(AMR)危机。在此背景下,具有悠久应用历史的噬菌体疗法因其独特优势,作为防控家禽产业链沙门菌感染、尤其是对抗多重耐药(MDR)菌株的关键策略,展现出广阔前景。现有研究和田间应用表明,噬菌体疗法具备良好的安全性基础:其高度宿主特异性可精准靶向沙门菌,避免对家禽组织及肠道共生菌群造成破坏;烈性噬菌体对真核细胞无毒性,商业化产品(如SalmoFREE®、Bafasal®)在实际应用中未报告显著不良反应。同时,噬菌体在降低家禽沙门菌载量、死亡率及改善生产性能方面表现出显著有效性,并在禽肉、禽蛋加工环节展现出强大的生物防控潜力。
然而,其从实验室迈向规模化应用仍面临一些瓶颈:噬菌体高度宿主特异性虽利于精准靶向,却也限制其应对混合感染,需通过开发噬菌体鸡尾酒疗法(组合不同噬菌体以拓宽裂解谱)或工程化改造扩展裂解谱的噬菌体来克服。细菌抗性突变可能导致治疗失效,对策包括采用鸡尾酒策略、与抗生素联用及组合靶向不同受体的噬菌体。此外,复杂的体内外环境(体内如胃肠道动态pH、菌群丰度与状态;体外如食品基质的理化特性、加工条件)显著影响噬菌体的存活、吸附、复制及裂解效率,需开发保护性递送系统(如微胶囊化)并加强药代动力学/药效学(PK/PD)研究以优化应用方案。
在食品防控领域,噬菌体应用虽已实现商业化并取得进展,但仍需针对不同禽肉、禽蛋产品特性及加工流程,优化噬菌体浓度、应用方式与时机,并深入评估食品基质效应(pH、温度、化学成分等)的长期影响,为精准应用与产业化提供科学支撑。同时,监管与标准化体系亟待完善,需在现有专家共识和团体标准基础上持续推进法规、质量控制和临床应用指南的建设。
未来研究应着重于:大规模田间试验验证全链条防控效力;深入探究噬菌体-宿主相互作用及抗性机制;挖掘新型噬菌体资源并推进工程化改造;开发高效递送系统;以及建立完善的监管与评估体系。随着这些挑战的逐步解决,噬菌体有望成为家禽产业链沙门菌防控的核心策略,为保障动物健康、食品安全和公共卫生安全提供强有力的绿色解决方案。
  • 中国博士后科学基金面上资助项目(2024MD763976)
  • 黑龙江省博士后面上资助项目(LBH-Z24246)
  • 黑龙江省自然科学基金资助项目(QC2025C037)
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2026年第57卷第3期
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doi: 10.11843/j.issn.0366-6964.2026.03.014
  • 接收时间:2025-07-31
  • 首发时间:2026-09-16
  • 出版时间:2026-03-23
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  • 收稿日期:2025-07-31
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中国博士后科学基金面上资助项目(2024MD763976)
黑龙江省博士后面上资助项目(LBH-Z24246)
黑龙江省自然科学基金资助项目(QC2025C037)
作者信息
    黑龙江八一农垦大学,大庆 163319

通讯作者:

高东阳,主要从事动物传染病诊断与防治研究,E-mail:
郑家三,主要从事奶牛肢蹄病病因学与综合防控研究,E-mail:
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2种不同金属材料的力学参数
科
Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)
属
Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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