{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:30:33Z","timestamp":1790789433460,"version":"4.1.0"},"reference-count":59,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2016,7,20]],"date-time":"2016-07-20T00:00:00Z","timestamp":1468972800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Hum Exp Toxicol"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:p>\n                    Probiotics are live microorganisms ingested for the purpose of conferring a health benefit on the host. Development of new probiotics includes the need for safety evaluations that should consider factors such as pathogenicity, infectivity, virulence factors, toxicity, and metabolic activity. Clostridium butyricum MIYAIRI 588\n                    <jats:sup>\u00ae<\/jats:sup>\n                    (CBM 588\n                    <jats:sup>\u00ae<\/jats:sup>\n                    ), an anaerobic spore-forming bacterium, has been developed as a probiotic for use by humans and food animals. Safety studies of this probiotic strain have been conducted and include assessment of antimicrobial sensitivity, documentation of the lack of Clostridium toxin genes, and evaluation of CBM 588\n                    <jats:sup>\u00ae<\/jats:sup>\n                    on reproductive and developmental toxicity in a rodent model. With the exception of aminoglycosides, to which anaerobes are intrinsically resistant, CBM 588\n                    <jats:sup>\u00ae<\/jats:sup>\n                    showed sensitivity to all antibiotic classes important in human and animal therapeutics. In addition, analysis of the CBM 588\n                    <jats:sup>\u00ae<\/jats:sup>\n                    genome established the absence of genes for encoding for \u03b1, \u03b2, or \u03b5 toxins and botulin neurotoxins types A, B, E, or F. There were no deleterious reproductive and developmental effects observed in mice associated with the administration of CBM 588\n                    <jats:sup>\u00ae<\/jats:sup>\n                    . These data provide further support for the safety of CBM 588\n                    <jats:sup>\u00ae<\/jats:sup>\n                    for use as a probiotic in animals and humans.\n                  <\/jats:p>","DOI":"10.1177\/0960327115607372","type":"journal-article","created":{"date-parts":[[2015,10,5]],"date-time":"2015-10-05T21:58:01Z","timestamp":1444082281000},"page":"818-832","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":51,"title":["Safety assessment of the\n                    <i>Clostridium butyricum<\/i>\n                    MIYAIRI 588\n                    <sup>\u00ae<\/sup>\n                    probiotic strain including evaluation of antimicrobial sensitivity and presence of\n                    <i>Clostridium<\/i>\n                    toxin genes in vitro and teratogenicity in vivo"],"prefix":"10.1177","volume":"35","author":[{"given":"K","family":"Isa","sequence":"first","affiliation":[{"name":"Miyarisan Pharmaceutical Co., Ltd, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Oka","sequence":"additional","affiliation":[{"name":"Miyarisan Pharmaceutical Co., Ltd, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Beauchamp","sequence":"additional","affiliation":[{"name":"Spherix Consulting, Rockville, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Sato","sequence":"additional","affiliation":[{"name":"Miyarisan Pharmaceutical Co., Ltd, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Wada","sequence":"additional","affiliation":[{"name":"Miyarisan Pharmaceutical Co., Ltd, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Ohtani","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Miyarisan Pharmaceutical Co., Ltd, Tokyo, Japan"},{"name":"Deceased"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"McCartney","sequence":"additional","affiliation":[{"name":"Pen & Tec Consulting, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Miyarisan Pharmaceutical Co., Ltd, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan"},{"name":"Deceased"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Kamiya","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Kruger","sequence":"additional","affiliation":[{"name":"Spherix Consulting, Rockville, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Miyarisan Pharmaceutical Co., Ltd, Tokyo, Japan"},{"name":"Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,7,20]]},"reference":[{"key":"bibr1-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1086\/523341"},{"key":"bibr2-0960327115607372","doi-asserted-by":"publisher","DOI":"10.4161\/gmic.1.3.12127"},{"key":"bibr3-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1086\/523331"},{"key":"bibr4-0960327115607372","doi-asserted-by":"publisher","DOI":"10.12938\/bmfh.32.81"},{"key":"bibr5-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1038\/jp.2014.234"},{"key":"bibr6-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1159\/000354891"},{"key":"bibr7-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afs077"},{"key":"bibr8-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1016\/j.pepo.2013.12.003"},{"key":"bibr9-0960327115607372","first-page":"e56","volume":"7","author":"Pattani R","year":"2013","journal-title":"Open Med"},{"key":"bibr10-0960327115607372","volume-title":"Guidelines for the evaluation of probiotics in food","author":"FAO and WHO","year":"2002"},{"issue":"9","key":"bibr11-0960327115607372","first-page":"412","volume":"71","author":"Barkay T","year":"2005","journal-title":"ASM News"},{"key":"bibr12-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1201\/9780203489819"},{"key":"bibr13-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198469"},{"key":"bibr14-0960327115607372","unstructured":"Mims C, Wakelin D, Playfair J, Medical microbiology. 2nd ed. London: Mosby International Limited, 1998, pp. 519\u2013521."},{"key":"bibr15-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1128\/mr.55.4.621-648.1991"},{"key":"bibr16-0960327115607372","doi-asserted-by":"crossref","unstructured":"Sugiyama H. Clostridium botulinum neurotoxin.\n                      Microbiol Rev\n                      1980; 44: 419\u2013448.","DOI":"10.1128\/mr.44.3.419-448.1980"},{"key":"bibr17-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1046\/j.1442-200X.2003.01671.x"},{"key":"bibr18-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsim.2004.03.010"},{"key":"bibr19-0960327115607372","unstructured":"EU. Commission Regulation (EC) No 903\/2009 of 28 September 2009 concerning the authorisation of the preparation of\n                      Clostridium butyricum\n                      MIYAIRI 588 (FERM-P 1467) as a feed additive for chickens for fattening (holder of authorisation Miyarisan Pharmaceutical Co. Ltd, represented by Mitsui & Co. Deutschland GmbH). Official Journal of the European Union L02\/10, http:\/\/eur-lex.europa.eu (2009, accessed 1 April 2015)."},{"key":"bibr20-0960327115607372","unstructured":"EU. Commission Implementing Regulation (EU) No 373\/2011 of 15 April 2011 concerning the authorisation of the preparation of\n                      Clostridium butyricum\n                      FERM-BP 2789 as a feed additive for minor avian species except laying birds, weaned piglets and minor porcine species (weaned) and amending Regulation (EC) No 903\/2009 (holder of authorisation Miyarisan Pharmaceutical Co. Ltd, represented by Miyarisan Pharmaceutical Europe S.L.U.). Official Journal of the European Union L02\/10, http:\/\/eur-lex.europa.eu (2011, accessed 1 April 2015)."},{"key":"bibr21-0960327115607372","unstructured":"EU. Commission Implementing Regulation (EU) No 1108\/2014 of 20 October 2014 concerning the authorisation of a preparation of\n                      Clostridium butyricum\n                      (FERM BP-2789) as a feed additive for turkeys for fattening and turkeys reared for breeding (holder of authorisation Miyarisan Pharmaceutical Co. Ltd represented by Miyarisan Pharmaceutical Europe S.L.U.). Official Journal of the European Union L301\/16, http:\/\/eur-lex.europa.eu (2014, accessed 1 April 2015)."},{"key":"bibr22-0960327115607372","unstructured":"EU. Commission Implementing Decision of 11 December 2014 authorising the placing on the market of\n                      Clostridium butyricum\n                      (CBM 588) as a novel food ingredient under Regulation (EC) No 258\/97 of the European Parliament and of the Council. Official Journal of the European Union L359\/153, http:\/\/eur-lex.europa.eu (2014, accessed 1 April 2015)."},{"key":"bibr23-0960327115607372","first-page":"215","volume":"34","author":"Yuzawa T","year":"1987","journal-title":"Pharmacometrics"},{"key":"bibr24-0960327115607372","first-page":"223","volume":"34","author":"Yuzawa T","year":"1987","journal-title":"Pharmacometrics"},{"key":"bibr25-0960327115607372","first-page":"683","volume":"33","author":"Yuzawa T","year":"1987","journal-title":"Pharmacometrics"},{"key":"bibr26-0960327115607372","doi-asserted-by":"publisher","DOI":"10.12938\/bifidus1982.7.1_56"},{"key":"bibr27-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.2005.tb03653.x"},{"key":"bibr28-0960327115607372","volume-title":"Methods for antimicrobial susceptibility testing of anaerobic bacteria; approved standard \u2013 eighth edition. CLSI document M11-A8","author":"CLSI","year":"2012"},{"key":"bibr29-0960327115607372","volume-title":"Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Second informational Supplement. CLSI document M100-S22","author":"CLSI","year":"2012"},{"key":"bibr30-0960327115607372","first-page":"115","volume-title":"Nucleic acid techniques in bacterial systematics","author":"Lane DJ.","year":"1991"},{"key":"bibr31-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.35.1.228-232.1997"},{"key":"bibr32-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.67.12.5694-5699.2001"},{"key":"bibr33-0960327115607372","volume-title":"Pharmaceutical guidelines for teratogenicity and reproductive toxicity studies","author":"Japan Ministry of Health and Welfare"},{"key":"bibr34-0960327115607372","doi-asserted-by":"publisher","DOI":"10.3109\/10520292609115636"},{"key":"bibr35-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1086\/429323"},{"key":"bibr36-0960327115607372","first-page":"2740","volume":"10","author":"EFSA","year":"2012","journal-title":"EFSA J"},{"key":"bibr37-0960327115607372","unstructured":"EUCAST. Breakpoint tables for interpretation of MICs and zone diameters, Version 2.0, valid from 2012-01-01, http:\/\/www.eucast.org\/clinical_breakpoints\/ (2012, accessed 20 July 2012)."},{"key":"bibr38-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2012.04.012"},{"key":"bibr39-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1007\/BF01575751"},{"key":"bibr40-0960327115607372","first-page":"1","volume":"1039","author":"EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP)","year":"2009","journal-title":"EFSA J"},{"key":"bibr41-0960327115607372","doi-asserted-by":"publisher","DOI":"10.2903\/j.efsa.2011.1951"},{"key":"bibr42-0960327115607372","doi-asserted-by":"publisher","DOI":"10.2903\/j.efsa.2013.3040"},{"key":"bibr43-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/8.suppl_D.1"},{"key":"bibr44-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2009.10.002"},{"key":"bibr45-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1992.tb05576.x"},{"key":"bibr46-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1007\/BF01567668"},{"key":"bibr47-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1099\/00222615-48-2-133"},{"key":"bibr48-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.35.8.2160-2162.1997"},{"key":"bibr49-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2007.08.013"},{"key":"bibr50-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/154.2.207"},{"key":"bibr51-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.23.1.201-202.1986"},{"key":"bibr52-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2002.tb11334.x"},{"key":"bibr53-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(92)91615-W"},{"key":"bibr54-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01180-06"},{"key":"bibr55-0960327115607372","first-page":"999","volume":"28","author":"Wang W","year":"2000","journal-title":"Jpn Pharmacol Ther"},{"key":"bibr56-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.66.11.4992-4997.2000"},{"key":"bibr57-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.59.11.3825-3831.1993"},{"key":"bibr58-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1128\/AM.27.1.251-258.1974"},{"key":"bibr59-0960327115607372","doi-asserted-by":"publisher","DOI":"10.1080\/10937400490512447"}],"container-title":["Human &amp; Experimental Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0960327115607372","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0960327115607372","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0960327115607372","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:48:36Z","timestamp":1777448916000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0960327115607372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,20]]},"references-count":59,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,8]]}},"alternative-id":["10.1177\/0960327115607372"],"URL":"https:\/\/doi.org\/10.1177\/0960327115607372","relation":{},"ISSN":["0960-3271","1477-0903"],"issn-type":[{"value":"0960-3271","type":"print"},{"value":"1477-0903","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,20]]}}}