title: Safety assessment of the Clostridium butyricum MIYAIRI 588® probiotic strain including evaluation of antimicrobial sensitivity and presence of Clostridium toxin genes in vitro and teratogenicity in vivo.
abstract: 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(®) (CBM 588(®)), 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(®) on reproductive and developmental toxicity in a rodent model. With the exception of aminoglycosides, to which anaerobes are intrinsically resistant, CBM 588(®) showed sensitivity to all antibiotic classes important in human and animal therapeutics. In addition, analysis of the CBM 588(®) genome established the absence of genes for encoding for α, β, or ε 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(®) These data provide further support for the safety of CBM 588(®) for use as a probiotic in animals and humans.
authors.affiliation: Miyarisan Pharmaceutical Co., Ltd, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Isa
authors.affiliation: Miyarisan Pharmaceutical Co., Ltd, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Oka
authors.affiliation: Spherix Consulting, Rockville, MD, USA.
authors.forename: N
authors.initials: N
authors.lastname: Beauchamp
authors.affiliation: Miyarisan Pharmaceutical Co., Ltd, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.affiliation: Miyarisan Pharmaceutical Co., Ltd, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Wada
authors.affiliation: Department of Bacteriology, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ohtani
authors.affiliation: Miyarisan Pharmaceutical Co., Ltd, Tokyo, Japan Deceased.
authors.forename: S
authors.initials: S
authors.lastname: Nakanishi
authors.affiliation: Pen & Tec Consulting, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: McCartney
authors.affiliation: Miyarisan Pharmaceutical Co., Ltd, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Bacteriology, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan Deceased.
authors.forename: T
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kamiya
authors.affiliation: Spherix Consulting, Rockville, MD, USA.
authors.forename: C
authors.initials: C
authors.lastname: Kruger
authors.affiliation: Miyarisan Pharmaceutical Co., Ltd, Tokyo, Japan Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan motomichi.takahashi@miyarisan.com.
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000235:genetics*; D001905:Botulinum Toxins / Q000235:genetics; D046972:Clostridium butyricum / Q000187:drug effects / Q000235:genetics*; D024881:Drug Resistance, Bacterial; D004768:Enterotoxins / Q000235:genetics; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D009498:Neurotoxins / Q000235:genetics; D011247:Pregnancy; D019936:Probiotics / Q000494:pharmacology / Q000592:standards / Q000633:toxicity*; D012098:Reproduction / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D004768:Enterotoxins; D009498:Neurotoxins; C035598:enterotoxin, Clostridium; D001905:Botulinum Toxins
keywords: CBM 588® probiotic; Clostridium butyricum MIYAIRI 588®; Clostridium toxins; antibiotic sensitivity; reproductive and developmental toxicity; teratogenicity