{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:27:11Z","timestamp":1787657231817,"version":"build-2736575974"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T00:00:00Z","timestamp":1562889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2017YFD0701700"],"award-info":[{"award-number":["2017YFD0701700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Fund of China","doi-asserted-by":"crossref","award":["31672673"],"award-info":[{"award-number":["31672673"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Fund of China","doi-asserted-by":"crossref","award":["31702391"],"award-info":[{"award-number":["31702391"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Fund of China","doi-asserted-by":"crossref","award":["31472312"],"award-info":[{"award-number":["31472312"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Liaoning S&T Project","award":["2017203002"],"award-info":[{"award-number":["2017203002"]}]},{"name":"Liaoning S&T Project","award":["2017203002"],"award-info":[{"award-number":["2017203002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Human-use probiotics have recently been associated with clinical infections and antibiotic resistance transfer, raising public concern over their safety. However, despite their extensive application in aquaculture and animal husbandry, the safety of animal-use probiotics remains poorly described.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We evaluated the safety of 92 animal-use probiotics from China. The pattern of spread of pathogens from probiotics and the consequent public health implications were also examined by conducting in-field genomic surveillance at 2 farms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 123 probiotic Bacillus species isolates were obtained from 92 brands of probiotics, of which 45 isolates were resistant to antibiotics. Notably, 33.7% of probiotic products were contaminated with life-threatening pathogens such as Klebsiella pneumoniae. Genomic surveillance at a chicken farm identified an anthrax toxin\u2013positive Bacillus cereus strain in a probiotic product used as a feed supplement, which was transferred into the groundwater and to a nearby fish farm. Following up retrospective analysis of the surveillance data during 2015\u20132018 in 3 provinces retrieved 2 B. cereus strains from human with intestinal anthrax symptoms and confirmed the transmission of B. cereus from farm to human. Surveillance of anthrax toxin revealed that cya was detected in 8 of 31 farms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study provides the first national safety survey of animal-use probiotics in China and confirms the spillover effects of probiotics from the farms to human. These results suggest that the large-scale application of pathogen-containing probiotics leads to the transfer of pathogens, with worrisome implications for public health. Good Manufacturing Practice should be implemented during the production of all probiotics.<\/jats:p>\n                  <jats:p>Animal-use probiotic products are frequently contaminated with viable pathogenic bacteria. This study revealed that virulent probiotic organisms and contaminating pathogens were colonized with farm animals and shed into the environment, which facilitated the transfer of pathogens to humans.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciz642","type":"journal-article","created":{"date-parts":[[2019,7,11]],"date-time":"2019-07-11T11:10:31Z","timestamp":1562843431000},"page":"2386-2395","source":"Crossref","is-referenced-by-count":36,"title":["National Safety Survey of Animal-use Commercial Probiotics and Their Spillover Effects From Farm to Humans: An Emerging Threat to Public Health"],"prefix":"10.1093","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1754-199X","authenticated-orcid":false,"given":"Songzhe","family":"Fu","sequence":"first","affiliation":[{"name":"College of Marine Technology and Environment, Dalian Ocean University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Animal Production, Ghent University, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenglan","family":"He","sequence":"first","affiliation":[{"name":"Nanchang Center for Disease Control and Prevention, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiting","family":"Lan","sequence":"first","affiliation":[{"name":"School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Hao","sequence":"first","affiliation":[{"name":"College of Fishery and Life Sciences, Dalian Ocean University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Ni","sequence":"first","affiliation":[{"name":"College of Fishery and Life Sciences, Dalian Ocean University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"first","affiliation":[{"name":"College of Marine Technology and Environment, Dalian Ocean University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijun","family":"Li","sequence":"first","affiliation":[{"name":"College of Fishery and Life Sciences, Dalian Ocean University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,12]]},"reference":[{"key":"2020052309495757000_CIT0001","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/nrgastro.2010.117","article-title":"Probiotics and the gut microbiota in intestinal health and disease","volume":"7","author":"Gareau","year":"2010","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2020052309495757000_CIT0002","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.nut.2017.06.024","article-title":"Probiotics and gastrointestinal conditions: an overview of evidence from the Cochrane Collaboration","volume":"45","author":"Parker","year":"2018","journal-title":"Nutrition"},{"key":"2020052309495757000_CIT0003","first-page":"509","article-title":"The promises and risks of probiotic Bacillus species","volume":"65","author":"Je\u017cewska-Fr\u0105ckowiak","year":"2018","journal-title":"Acta Biochim Pol"},{"key":"2020052309495757000_CIT0004","doi-asserted-by":"crossref","DOI":"10.1128\/microbiolspec.PFS-0012-2016","article-title":"Current status of the preharvest application of pro- and prebiotics to farm animals to enhance the microbial safety of animal products","volume":"5","author":"Joerger","year":"2017","journal-title":"Microbiol Spectr"},{"key":"2020052309495757000_CIT0005","article-title":"Effect of probiotics on the meat flavour and gut microbiota of chicken","volume":"7","author":"Wang","year":"2017","journal-title":"Sci Rep"},{"key":"2020052309495757000_CIT0006","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.femsre.2004.12.001","article-title":"The use of bacterial spore formers as probiotics","volume":"29","author":"Hong","year":"2005","journal-title":"FEMS Microbiol Rev"},{"key":"2020052309495757000_CIT0007","doi-asserted-by":"crossref","first-page":"718","DOI":"10.3389\/fmicb.2016.00718","article-title":"Probiotic Bacillus cereus strains, a potential risk for public health in China","volume":"7","author":"Zhu","year":"2016","journal-title":"Front Microbiol"},{"key":"2020052309495757000_CIT0008","doi-asserted-by":"crossref","first-page":"164","DOI":"10.4161\/gmic.1.3.12127","article-title":"Safety assessment of probiotics for human use","volume":"1","author":"Sanders","year":"2010","journal-title":"Gut Microbes"},{"key":"2020052309495757000_CIT0009","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1001\/jamainternmed.2018.5403","article-title":"Probiotic safety\u2014no guarantees","volume":"178","author":"Cohen","year":"2018","journal-title":"JAMA Intern Med"},{"key":"2020052309495757000_CIT0010","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1128\/JCM.36.1.325-326.1998","article-title":"Recurrent septicemia in an immunocompromised patient due to probiotic strains of Bacillus subtilis","volume":"36","author":"Oggioni","year":"1998","journal-title":"J Clin Microbiol"},{"key":"2020052309495757000_CIT0011","first-page":"155","article-title":"Fatal gastrointestinal mucormycosis in a premature infant associated with a contaminated dietary supplement\u2014Connecticut, 2014","volume":"64","author":"Vallabhaneni","year":"2015","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2020052309495757000_CIT0012","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3389\/fmicb.2013.00202","article-title":"Antibiotic resistance in probiotic bacteria","volume":"4","author":"Gueimonde","year":"2013","journal-title":"Front Microbiol"},{"key":"2020052309495757000_CIT0013","doi-asserted-by":"crossref","first-page":"4595","DOI":"10.1007\/s00253-016-7416-9","article-title":"Integrate genome-based assessment of safety for probiotic strains: Bacillus coagulans GBI-30, 6086 as a case study","volume":"100","author":"Salvetti","year":"2016","journal-title":"Appl Microbiol Biotechnol"},{"key":"2020052309495757000_CIT0014","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/zph.12083","article-title":"The evidentiary value of challenge trials for three pre-harvest food safety topics: a systematic assessment","volume":"61","author":"Wisener","year":"2014","journal-title":"Zoonoses Public Health"},{"key":"2020052309495757000_CIT0015","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1093\/jac\/dks391","article-title":"BSAC standardized disc susceptibility testing method (version 11)","volume":"67","author":"Howe","year":"2012","journal-title":"J Antimicrob Chemother"},{"key":"2020052309495757000_CIT0016","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1128\/AEM.70.1.191-201.2004","article-title":"Multilocus sequence typing scheme for bacteria of the Bacillus cereus group","volume":"70","author":"Helgason","year":"2004","journal-title":"Appl Environ Microbiol"},{"key":"2020052309495757000_CIT0017","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.compbiolchem.2016.09.004","article-title":"SnpFilt: a pipeline for reference-free assembly-based identification of SNPs in bacterial genomes","volume":"65","author":"Chan","year":"2016","journal-title":"Comput Biol Chem"},{"key":"2020052309495757000_CIT0018","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1093\/bioinformatics\/btl446","article-title":"RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models","volume":"22","author":"Stamatakis","year":"2006","journal-title":"Bioinformatics"},{"key":"2020052309495757000_CIT0019","first-page":"2199","article-title":"Review: the market of probiotics","volume":"28","author":"Di Cerbo","year":"2015","journal-title":"Pak J Pharm Sci"},{"key":"2020052309495757000_CIT0020","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1128\/AEM.69.4.2372-2376.2003","article-title":"Production of diarrheal enterotoxins and other potential virulence factors by veterinary isolates of Bacillus species associated with nongastrointestinal infections","volume":"69","author":"Rowan","year":"2003","journal-title":"Appl Environ Microbiol"},{"key":"2020052309495757000_CIT0021","doi-asserted-by":"crossref","first-page":"S129","DOI":"10.1093\/cid\/civ085","article-title":"Risk and safety of probiotics","volume":"60","author":"Doron","year":"2015","journal-title":"Clin Infect Dis"},{"key":"2020052309495757000_CIT0022","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.fsi.2015.05.038","article-title":"Probiotics and prebiotics associated with aquaculture: a review","volume":"45","author":"Akhter","year":"2015","journal-title":"Fish Shellfish Immunol"},{"key":"2020052309495757000_CIT0023","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1007\/s10096-016-2644-6","article-title":"Deep sequencing approach for investigating infectious agents causing fever","volume":"35","author":"Susilawati","year":"2016","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2020052309495757000_CIT0024","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.jiac.2017.04.001","article-title":"Bacteremia caused by the photosynthetic environmental bacterium Rhodopseudomonas","volume":"23","author":"Mitchell","year":"2017","journal-title":"J Infect Chemother"},{"key":"2020052309495757000_CIT0025","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s10096-004-1253-y","article-title":"Pathogenic relevance of Lactobacillus: a retrospective review of over 200 cases","volume":"24","author":"Cannon","year":"2005","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2020052309495757000_CIT0026","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.nmni.2015.11.008","article-title":"Report of the first Vagococcus lutrae human infection, Marseille, France","volume":"9","author":"Garcia","year":"2016","journal-title":"New Microbes New Infect"},{"key":"2020052309495757000_CIT0027","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.fsi.2014.11.037","article-title":"The in vitro immunomodulatory effect of extracellular products (ECPs) of Vagococcus fluvialis L21 on European sea bass (Dicentrarchus labrax) leucocytes","volume":"42","author":"Rom\u00e1n","year":"2015","journal-title":"Fish Shellfish Immunol"},{"key":"2020052309495757000_CIT0028","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1002\/mnfr.201300065","article-title":"Microbial characterization of probiotics\u2014advisory report of the Working Group \u201c8651 Probiotics\u201d of the Belgian Superior Health Council (SHC)","volume":"57","author":"Huys","year":"2013","journal-title":"Mol Nutr Food Res"},{"key":"2020052309495757000_CIT0029","doi-asserted-by":"crossref","first-page":"3247","DOI":"10.3389\/fmicb.2018.03247","article-title":"Lactobacillus dominate in the intestine of Atlantic salmon fed dietary probiotics","volume":"9","author":"Gupta","year":"2018","journal-title":"Front Microbiol"},{"key":"2020052309495757000_CIT0030","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.chom.2019.02.005","article-title":"Adaptive strategies of the candidate probiotic E. coli Nissle in the mammalian gut","volume":"25","author":"Crook","year":"2019","journal-title":"Cell Host Microbe"},{"key":"2020052309495757000_CIT0031","doi-asserted-by":"crossref","DOI":"10.1128\/genomeA.01741-15","article-title":"Genome sequence of Bacillus pumilus strain Bonn, isolated from an anthrax-like necrotic skin infection site of a child","volume":"4","author":"Grass","year":"2016","journal-title":"Genome Announc"},{"key":"2020052309495757000_CIT0032","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.fm.2013.08.010","article-title":"Genetic characterization of antibiotic resistance and virulence factors in Enterococcus spp. from Japanese retail ready-to-eat raw fish","volume":"38","author":"Hammad","year":"2014","journal-title":"Food Microbiol"},{"key":"2020052309495757000_CIT0033","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1007\/s40572-016-0089-9","article-title":"Recent research examining links among Klebsiella pneumoniae from food, food animals, and human extraintestinal infections","volume":"3","author":"Davis","year":"2016","journal-title":"Curr Environ Health Rep"},{"key":"2020052309495757000_CIT0034","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1089\/fpd.2017.2393","article-title":"A systematic review of bacterial foodborne outbreaks related to red meat and meat products","volume":"15","author":"Omer","year":"2018","journal-title":"Foodborne Pathog Dis"},{"key":"2020052309495757000_CIT0035","doi-asserted-by":"crossref","first-page":"288","DOI":"10.4315\/0362-028X-40.5.288","article-title":"Effect of feeding lactobacilli on the coliform and Lactobacillus flora of intestinal tissue and feces from piglets","volume":"40","author":"Muralidhara","year":"1977","journal-title":"J Food Prot"},{"key":"2020052309495757000_CIT0036","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nrmicro2312","article-title":"Call of the wild: antibiotic resistance genes in natural environments","volume":"8","author":"Allen","year":"2010","journal-title":"Nat Rev Microbiol"},{"key":"2020052309495757000_CIT0037","doi-asserted-by":"crossref","first-page":"3352","DOI":"10.1128\/JCM.00561-06","article-title":"Characterization of Bacillus cereus isolates associated with fatal pneumonias: strains are closely related to Bacillus anthracis and harbor B. anthracis virulence genes","volume":"44","author":"Hoffmaster","year":"2006","journal-title":"J Clin Microbiol"},{"key":"2020052309495757000_CIT0038","doi-asserted-by":"crossref","first-page":"e0156987","DOI":"10.1371\/journal.pone.0156987","article-title":"Anthrax toxin-expressing Bacillus cereus isolated from an anthrax-like eschar","volume":"11","author":"Marston","year":"2016","journal-title":"PLoS One"},{"key":"2020052309495757000_CIT0039","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1139\/W08-022","article-title":"Safety evaluation of two bacterial strains used in Asian probiotic products","volume":"54","author":"Tompkins","year":"2008","journal-title":"Can J Microbiol"},{"key":"2020052309495757000_CIT0040","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.3389\/fmicb.2018.02216","article-title":"Genomic characterization and probiotic potency of Bacillus sp. DU-106, a highly effective producer of L-lactic acid isolated from fermented yogurt","volume":"9","author":"Li","year":"2018","journal-title":"Front Microbiol"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciz642\/30109385\/ciz642.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/cid\/article-pdf\/70\/11\/2386\/33290484\/ciz642.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/cid\/article-pdf\/70\/11\/2386\/33290484\/ciz642.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,23]],"date-time":"2020-05-23T13:50:29Z","timestamp":1590241829000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/70\/11\/2386\/5531897"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,12]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,7,12]]},"published-print":{"date-parts":[[2020,5,23]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciz642","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,6,1]]},"published":{"date-parts":[[2019,7,12]]}}}