Safety assessment of Bacillus subtilis CU1 for use as a probiotic in humans.
Bacillus subtilis CU1 is a recently described probiotic strain with beneficial effects on immune health in elderly subjects. The following work describes a series of studies supporting the safety of the strain for use as an ingredient in food and supplement preparations. Using a combination of 16S rDNA and gyrB nucleotide analyses, the species was identified as a member of the Bacillus subtilis complex (B. subtilis subsp. spizizenii). Further characterization of the organism at the strain level was achieved using random amplified polymorphic DNA polymerase chain reaction (RAPD PCR) and pulsed field gel electrophoresis (PFGE) analyses. B. subtilis CU1 did not demonstrate antibiotic resistance greater than existing regulatory cutoffs against clinically important antibiotics, did not induce hemolysis or produce surfactant factors, and was absent of toxigenic activity in vitro. Use of B. subtilis CU1 as a probiotic has recently been evaluated in a 16-week randomized, double-blind, placebo-controlled, parallel-arm study, in which 2 × 109spores per day of B. subtilis CU1 were administered for a total 40 days to healthy elderly subjects (4 consumption periods of 10 days separated by 18-day washouts). This work describes safety related endpoints not previously reported. B. subtilis CU1 was safe and well-tolerated in the clinical subjects without undesirable physiological effects on markers of liver and kidney function, complete blood counts, hemodynamic parameters, and vital signs.
Lesaffre Human Care, Lesaffre Group, 137 Rue Gabriel Péri, F-59700, Marcq-en-Baroeul, France. Electronic address: mle@ennolys.fr.
Marie
M
Lefevre
University of Bordeaux, UMR 5248, Bordeaux Sci Agro, Gradignan, France.
Silvia M
SM
Racedo
University of Bordeaux, UMR 5248, Bordeaux Sci Agro, Gradignan, France.
Muriel
M
Denayrolles
University of Bordeaux, UMR 5248, Bordeaux Sci Agro, Gradignan, France.
Gabrielle
G
Ripert
Lesaffre Human Care, Lesaffre Group, 137 Rue Gabriel Péri, F-59700, Marcq-en-Baroeul, France.
Thomas
T
Desfougères
Intertek Scientific & Regulatory Consultancy, 2233 Argentia Rd., Suite 201, Mississauga, ON, L5N 2X7, Canada.
Alexandra R
AR
Lobach
Intertek Scientific & Regulatory Consultancy, 2233 Argentia Rd., Suite 201, Mississauga, ON, L5N 2X7, Canada.
Ryan
R
Simon
Lesaffre Human Care, Lesaffre Group, 137 Rue Gabriel Péri, F-59700, Marcq-en-Baroeul, France.
Fanny
F
Pélerin
Lesaffre Human Care, Lesaffre Group, 137 Rue Gabriel Péri, F-59700, Marcq-en-Baroeul, France.
Peter
P
Jüsten
University of Bordeaux, UMR 5248, Bordeaux Sci Agro, Gradignan, France.
Maria C
MC
Urdaci
D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D003257:Consumer Product Safety; D016172:DNA Fingerprinting; D027081:DNA Gyrase / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D004311:Double-Blind Method; D024881:Drug Resistance, Bacterial; D016521:Electrophoresis, Gel, Pulsed-Field; D005260:Female; D059022:Food Safety; D006461:Hemolysis; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D019936:Probiotics / Q000633:toxicity*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D021521:Ribotyping; D018570:Risk Assessment; D013997:Time Factors
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S; D027081:DNA Gyrase
Bacillus subtilis; Clinical study; Food safety; Human; Safety; probiotic