Safety Assessment of Bacillus subtilis MB40 for Use in Foods and Dietary Supplements
Abstract
:1. Introduction
2. Materials and Methods
2.1. Test Article
2.2. Enterotoxin Screen (In Silico)
2.3. Enterotoxin Screen (In Vitro)
2.4. Antibiotic Sensitivity Testing
2.5. Minimum Inhibitory Concentration
2.6. Oral Toxicity Study in Rats
2.7. Human Clinical Safety and Tolerability Trial (Single-Blind Design)
3. Results
3.1. Subsection Enterotoxin Screens (In Silico)
3.2. Enterotoxin Screens (In Vitro)
3.3. Antibiotic Sensitivity Testing (AST)
3.4. Oral Toxicity Study in Rats
3.5. Human Clinical Safety and Tolerability Trial
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Test Group | Disc Code | Inhibition Zone (mm) | Zone Interpretation |
---|---|---|---|
Aminoglycosides | |||
Kanamycin | K 30 | 35 | S |
Gentamicin | GM 10 | 33 | S |
Neomycin | N 30 | 29 | S |
Streptomycin | S 10 | 15 | S |
b-Lactams: Penicillins | |||
Penicillin | P 10 | 29 | S |
Ampicillin | AM 10 | 28 | Int |
Amoxicillin/Clavulanic Acid | AmC 30 | 31 | S |
b-Lactams: Cephems | |||
Cephalothin | CF 30 | 52 | S |
Cefotaxime | CTX 30 | 25 | S |
Cefaclor | CEC 30 | 50 | S |
Ceftriaxone | CRO 30 | 26 | S |
Fluorquinolones | |||
Ciprofloxacin | CIP 5 | 30 | S |
Fosfomycins | |||
Fosfomycin + Glucose-6-Phosphate | FOS 200 | 6 | R |
Folate Pathway Inhibitors | |||
Sulfamethoxazole Trimethorprim | SXT | 32 | S |
Glycopeptides | |||
Vancomycin | Va 5 | 17 | S |
Macrolides, Lincosamides, Streptogramins | |||
Clindamycin | CC 2 | 22 | S |
Erythromycin | E 15 | 33 | S |
Quinupristin/Dalfopristin | SYN 15 | 20 | S |
Phenicols | |||
Chloramphenicol | C 30 | 30 | S |
Rifampin | |||
Rifampin | RA 5 | 18 | Int |
Tetracyclines | |||
Tetracycline | Te 30 | 19 | S |
Antibiotic | MIC (µg/mL) | |||
---|---|---|---|---|
EFSA Cut-off Values for Bacillus [36] | MB40 | S. aureus | E. faecalis | |
Vancomycin | 4 | 0.5 | 1 | |
Gentamicin | 4 | 0.125 | 0.25 | |
Kanamycin | 8 | 1 | 2 | |
Streptomycin | 8 | >32 | N/A | 32 * |
Erythromycin | 4 | 0.125 | 0.25 | |
Clindamycin | 4 | 2 | 0.125 | |
Tetracycline | 8 | 4 | 0.5 | |
Chloramphenicol | 8 | 4 | 8 |
Parameter | Units | Group and Dose (mg/kg bw/day) | |||||||
---|---|---|---|---|---|---|---|---|---|
Males | Females | ||||||||
Control n 2 = 9 | 500 n = 10 | 1000 n 2 = 9 | 2000 n = 10 | Control n = 10 | 500 n 2 = 8 | 1000 n 2 = 8 | 2000 n = 10 | ||
WBC | ×103/µL | 10.36 ± 1.70 | 10.22 ± 2.47 | 10.27 ± 2.43 | 9.91 ± 2.24 | 6.84 ± 2.08 | 6.86 ± 1.79 | 7.10 ± 1.77 | 7.66 ± 2.00 |
RBC | ×106/µL | 7.45 ± 0.35 | 7.83 ± 0.29 * | 7.71 ± 0.34 | 7.53 ± 0.28 | 7.98 ± 0.33 | 7.73 ± 0.52 | 7.89 ± 0.37 | 7.86 ± 0.36 |
HGB | g/dL | 15.2 ± 0.56 | 15.6 ± 0.62 | 15.5 ± 0.57 | 15.2 ± 0.56 | 16.1 ± 0.74 | 15.6 ± 0.49 | 15.8 ± 0.41 | 15.7 ± 0.59 |
HCT | % | 46.2 ± 1.65 | 47.7 ± 2.04 | 47.3 ± 1.42 | 46.5 ± 1.60 | 47.2 ± 2.68 | 45.7 ± 1.69 | 46.7 ± 1.12 | 46.8 ± 1.92 |
MCV | fL | 62.2 ± 1.23 | 60.9 ± 2.25 | 61.4 ± 1.19 | 61.8 ± 1.58 | 59.1 ± 1.29 | 59.3 ± 2.23 | 59.3 ± 1.66 | 59.6 ± 1.68 |
MCH | pg | 20.4 ± 0.45 | 19.9 ± 0.81 | 20.2 ± 0.47 | 20.3 ± 0.55 | 20.1 ± 0.39 | 20.3 ± 0.96 | 20.1 ± 0.66 | 20.0 ± 0.51 |
MCHC | g/dL | 32.9 ± 0.52 | 32.7 ± 0.61 | 32.8 ± 0.65 | 32.8 ± 0.51 | 34.1 ± 0.54 | 34.2 ± 0.64 | 33.9 ± 0.57 | 33.6 ± 0.44 |
RDW | % | 12.4 ± 0.30 | 12.6 ± 0.41 | 12.6 ± 0.57 | 12.4 ± 0.42 | 11.3 ± 0.35 | 11.3 ± 0.35 | 11.2 ± 0.23 | 11.3 ± 0.32 |
HDW | g/dL | 1.96 ± 0.07 | 1.96 ± 0.25 | 1.86 ± 0.13 | 1.90 ± 0.07 | 1.97 ± 0.10 | 1.92 ± 0.12 | 1.95 ± 0.11 | 1.93 ± 0.08 |
MPV | fL | 7.44 ± 0.37 | 7.39 ± 0.23 | 7.39 ± 0.28 | 7.22 ± 0.38 | 6.95 ± 0.31 | 6.83 ± 0.23 | 6.98 ± 0.36 | 6.87 ± 0.26 |
PLT | ×10³/µL | 948 ± 108.6 | 929 ± 171.3 | 762 ± 240.1 | 997 ± 212.9 | 898 ± 155.2 | 1007 ± 139.5 | 887 ± 310.2 | 1047 ± 119.5 |
ANEU | ×10³/µL | 1.38 ± 0.22 | 2.09 ± 1.99 | 1.79 ± 0.68 | 1.51 ± 0.22 | 1.04 ± 0.26 | 1.26 ± 0.41 | 1.18 ± 0.40 | 1.21 ± 0.43 |
ALYM | ×10³/µL | 8.59 ± 1.48 | 7.68 ± 1.85 | 8.09 ± 1.90 | 8.02 ± 2.17 | 5.55 ± 2.17 | 5.37 ± 1.67 | 5.68 ± 1.60 | 6.13 ± 1.88 |
AMON | ×10³/µL | 0.23 ± 0.07 | 0.23 ± 0.10 | 0.21 ± 0.07 | 0.22 ± 0.09 | 0.10 ± 0.02 | 0.11 ± 0.04 | 0.10 ± 0.03 | 0.16 ± 0.10 |
AEOS | ×10³/µL | 0.07 ± 0.03 | 0.13 ± 0.07 * | 0.11 ± 0.07 | 0.07 ± 0.03 | 0.11 ± 0.06 | 0.07 ± 0.02 | 0.09 ± 0.05 | 0.09 ± 0.06 |
ABAS | ×10³/µL | 0.02 ± 0.01 | 0.02 ± 0.01 | 0.02 ± 0.01 | 0.02 ± 0.01 | 0.01 ± 0.01 | 0.01 ± 0.01 | 0.01 ± 0.01 | 0.02 ± 0.01 |
ALUC | ×10³/µL | 0.07 ± 0.03 | 0.06 ± 0.02 | 0.06 ± 0.01 | 0.07 ± 0.03 | 0.04 ± 0.02 | 0.04 ± 0.01 | 0.04 ± 0.02 | 0.06 ± 0.03 |
ARET | ×10³/µL | 257 ± 25.8 | 290 ± 83.2 | 252 ± 37.3 | 242 ± 35.7 | 185 ± 38.4 | 195 ± 33.9 | 177 ± 20.2 | 188.8 ± 30.9 |
PT 1 | sec | 16.5 ± 0.54 | 17.8 ± 0.71 † | 18.2 ± 0.61 † | 18.0 ± 0.78 † | 16.0 ± 0.81 | 16.9 ± 1.09 * | 16.5 ± 0.66 | 16.9 ± 0.63 |
APTT 1 | sec | 11.7 ± 0.80 | 10.9 ± 0.87 | 10.9 ± 0.79 | 11.0 ± 1.07 | 11.5 ± 1.12 | 11.2 ± 0.58 | 11.6 ± 1.17 | 12.1 ± 1.51 |
Parameter | Units | Group and Dose (mg/kg bw/day) | |||||||
---|---|---|---|---|---|---|---|---|---|
Males | Females | ||||||||
Control n = 10 | 500 n = 10 | 1000 n = 10 | 2000 n = 10 | Control n = 10 | 500 n = 10 | 1000 n = 10 | 2000 n = 10 | ||
ALB | g/dL | 3.7 ± 0.13 | 3.8 ± 0.16 | 3.6 ± 0.12 | 3.6 ± 0.13 | 4.1 ± 0.18 | 4.1 ± 0.13 | 4.2 ± 0.13 | 4.2 ± 0.16 |
TP | g/dL | 6.0 ± 0.23 | 6.0 ± 0.24 | 5.9 ± 0.19 | 5.8 ± 0.26 | 6.5 ± 0.26 | 6.5 ± 0.21 | 6.6 ± 0.21 | 6.5 ± 0.23 |
GLOB | g/dL | 2.3 ± 0.14 | 2.3 ± 0.13 | 2.3 ± 0.16 | 2.2 ± 0.13 | 2.4 ± 0.11 | 2.4 ± 0.09 | 2.4 ± 0.13 | 2.4 ± 0.16 |
ALB/GLOB | 1.66 ± 0.10 | 1.67 ± 0.10 | 1.63 ± 0.13 | 1.62 ± 0.06 | 1.72 ± 0.08 | 1.73 ± 0.07 | 1.77 ± 0.11 | 1.76 ± 0.14 | |
ALT | U/L | 43 ± 10.0 | 39 ± 3.9 | 38 ± 3.4 | 39 ± 4.2 | 24 ± 3.0 | 29 ± 4.4 * | 26 ± 4.1 | 29 ± 3.6 * |
AST | U/L | 115 ± 16.7 | 109 ± 34.7 | 106 ± 21.7 | 102 ± 20.7 | 104 ± 18.4 | 125 ± 30.7 | 103 ± 25.0 | 116 ± 21.6 |
ALP | U/L | 256 ± 48.5 | 291 ± 53.1 | 291 ± 60.3 | 260 ± 45.3 | 151 ± 35.7 | 167 ± 53.7 | 153 ± 30.6 | 151 ± 52.5 |
GGT | U/L | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 |
SDH | U/L | 10 ± 5.6 | 9 ± 2.7 | 8 ± 2.5 | 7 ± 2.2 | 12 ± 7.8 | 9 ± 4.6 | 10 ± 3.2 | 12 ± 7.4 |
TBIL | mg/dL | 0.00 ± 0.00 | 0.01 ± 0.03 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 |
CREAT | mg/dL | 0.22 ± 0.03 | 0.22 ± 0.03 | 0.21 ± 0.03 | 0.20 ± 0.03 | 0.33 ± 0.07 | 0.32 ± 0.04 | 0.30 ± 0.02 | 0.34 ± 0.06 |
BUN | mg/dL | 12.5 ± 0.83 | 12.6 ± 1.55 | 12.4 ± 1.66 | 12.6 ± 1.49 | 15.8 ± 1.69 | 17.4 ± 1.70 | 16.9 ± 3.12 | 16.8 ± 1.87 |
Ca | mg/dL | 10.7 ± 0.28 | 10.6 ± 0.33 | 10.5 ± 0.26 | 10.5 ± 0.27 | 10.3 ± 0.16 | 10.2 ± 0.16 | 10.3 ± 0.21 | 10.3 ± 0.25 |
Cl | mEq/L | 104 ± 1.1 | 104 ± 1.4 | 104 ± 1.2 | 104 ± 0.7 | 108 ± 1.0 | 108 ± 0.8 | 107 ± 1.5 | 106 ± 2.0 |
PHOS | mg/dL | 9.9 ± 0.42 | 9.7 ± 0.53 | 9.7 ± 0.57 | 9.4 ± 0.31 | 7.5 ± 0.64 | 7.7 ± 0.57 | 7.4 ± 0.66 | 8.0 ± 0.84 |
K | mEq/L | 5.63 ± 0.46 | 5.40 ± 0.43 | 5.37 ± 0.42 | 5.38 ± 0.28 | 5.31 ± 0.56 | 5.08 ± 0.56 | 5.04 ± 0.34 | 5.11 ± 0.40 |
Na | mEq/L | 144 ± 0.7 | 144 ± 1.2 | 144 ± 1.2 | 144 ± 1.2 | 145 ± 1.4 | 145 ± 0.7 | 144 ± 1.1 | 144 ± 1.2 |
GLU | mg/dL | 97 ± 4.8 | 106 ± 13.3 | 101 ± 8.3 | 104 ± 11.0 | 105 ± 6.9 | 106 ± 8.3 | 106 ± 7.9 | 103 ± 12.7 |
CHOL | mg/dL | 67 ± 12.7 | 72 ± 13.6 | 64 ± 8.1 | 64 ± 12.1 | 62 ± 15.7 | 55 ± 7.4 | 60 ± 16.3 | 64 ± 9.4 |
TRIG | mg/dL | 60 ± 17.0 | 62 ± 19.0 | 62 ± 21.5 | 56 ± 10.9 | 25 ± 3.5 | 22 ± 4.6 | 26 ± 7.1 | 26 ± 8.1 |
Parameter | Units | Group and Dose (mg/kg bw/day) | |||||||
---|---|---|---|---|---|---|---|---|---|
Males | Females | ||||||||
Control n = 10 | 500 n = 10 | 1000 n = 10 | 2000 n = 10 | Control n = 10 | 500 n = 10 | 1000 n = 10 | 2000 n = 10 | ||
SPGRAV | 1.023 ± 0.011 | 1.028 ± 0.013 | 1.028 ± 0.012 | 1.032 ± 0.016 | 1.032 ± 0.014 | 1.034 ± 0.016 | 1.029 ± 0.007 | 1.027 ± 0.009 | |
pH | 7.2 ± 0.48 | 7.3 ± 0.54 | 7.3 ± 0.42 | 7.1 ± 0.37 | 6.0 ± 0.28 | 5.9 ± 0.30 | 6.0 ± 0.24 | 5.9 ± 0.22 | |
UROBIL | mg/dL | 0.2 ± 0.00 | 0.2 ± 0.00 | 0.2 ± 0.00 | 0.2 ± 0.00 | 0.2 ± 0.00 | 0.2 ± 0.00 | 0.2 ± 0.00 | 0.2 ± 0.00 |
TVOL | mL | 9.1 ± 3.70 | 9.1 ± 5.93 | 8.2 ± 4.85 | 6.8 ± 3.91 | 6.1 ± 4.86 | 7.1 ± 7.39 | 6.0 ± 2.49 | 7.0 ± 4.18 |
Parameter | Units | Group and Dose (mg/kg bw/day) | |||||||
---|---|---|---|---|---|---|---|---|---|
Males | Females | ||||||||
Control n = 10 | 500 n = 10 | 1000 n = 10 | 2000 n = 10 | Control n = 10 | 500 n = 10 | 1000 n = 10 | 2000 n = 10 | ||
TBW | g | 311 ± 28.8 | 322 ± 24.2 | 318 ± 24.0 | 312 ± 20.2 | 204 ± 15.2 | 206 ± 15.4 | 208 ± 11.4 | 208 ± 17.5 |
Adrenals | g | 0.048 ± 0.006 | 0.056 ± 0.005 † | 0.054 ± 0.004 | 0.055 ± 0.007 * | 0.061 ± 0.008 | 0.066 ± 0.007 | 0.060 ± 0.007 | 0.066 ± 0.007 |
Adrenals/TBW | g/100 g | 0.016 ± 0.002 | 0.018 ± 0.002 | 0.017 ± 0.001 | 0.018 ± 0.002 | 0.030 ± 0.003 | 0.032 ± 0.004 | 0.029 ± 0.004 | 0.032 ± 0.002 |
Adrenals/TBRW | g/100 g | 2.550 ± 0.282 | 2.965 ± 0.310 † | 2.769 ± 0.201 | 2.836 ± 0.344 | 3.306 ± 0.434 | 3.545 ± 0.384 | 3.232 ± 0.336 | 3.620 ± 0.314 |
Brain | g | 1.88 ± 0.08 | 1.91 ± 0.07 | 1.94 ± 0.08 | 1.94 ± 0.06 | 1.85 ± 0.07 | 1.87 ± 0.08 | 1.86 ± 0.07 | 1.83 ± 0.07 |
Brain/TBW | g/100 g | 0.609 ± 0.052 | 0.595 ± 0.050 | 0.614 ± 0.048 | 0.622 ± 0.038 | 0.910 ± 0.053 | 0.910 ± 0.081 | 0.897 ± 0.044 | 0.885 ± 0.066 |
Heart | g | 1.32 ± 0.15 | 1.39 ± 0.17 | 1.32 ± 0.16 | 1.31 ± 0.10 | 0.90 ± 0.10 | 0.91 ± 0.06 | 0.99 ± 0.14 | 0.94 ± 0.09 |
Heart/TBW | g/100 g | 0.424 ± 0.034 | 0.431 ± 0.037 | 0.414 ± 0.038 | 0.420 ± 0.026 | 0.442 ± 0.034 | 0.441 ± 0.030 | 0.478 ± 0.083 | 0.451 ± 0.040 |
Heart/TBRW | g/100 g | 69.964 ± 8.010 | 72.815 ± 8.187 | 67.761 ± 7.615 | 67.699 ± 5.146 | 48.757 ± 4.738 | 48.616 ± 3.470 | 53.345 ± 8.818 | 51.131 ± 4.620 |
Kidneys | g | 2.71 ± 0.27 | 2.74 ± 0.22 | 2.69 ± 0.18 | 2.76 ± 0.27 | 1.69 ± 0.13 | 1.78 ± 0.19 | 1.73 ± 0.08 | 1.77 ± 0.14 |
Kidneys/TBW | g/100 g | 0.871 ± 0.051 | 0.852 ± 0.039 | 0.848 ± 0.054 | 0.882 ± 0.049 | 0.829 ± 0.042 | 0.863 ± 0.075 | 0.836 ± 0.031 | 0.851 ± 0.065 |
Kidneys/TBRW | g/100 g | 143.784 ± 13.822 | 144.088 ± 14.090 | 138.610 ± 10.194 | 142.450 ± 14.074 | 91.257 ± 4.822 | 95.578 ± 11.958 | 93.285 ± 4.083 | 96.257 ± 6.595 |
Liver | g | 12.03 ± 1.44 | 12.17 ± 1.06 | 11.69 ± 1.12 | 11.83 ± 1.24 | 7.30 ± 0.75 | 7.70 ± 0.63 | 7.59 ± 0.61 | 7.91 ± 0.66 |
Liver/TBW | g/100 g | 3.862 ± 0.224 | 3.788 ± 0.304 | 3.677 ± 0.167 | 3.784 ± 0.253 | 3.569 ± 0.216 | 3.738 ± 0.216 | 3.655 ± 0.208 | 3.810 ± 0.255 |
Liver/TBRW | g/100 g | 638.137 ± 65.444 | 639.713 ± 64.238 | 602.730 ± 59.382 | 611.639 ± 69.043 | 393.042 ± 28.612 | 413.189 ± 36.288 | 407.813 ± 22.574 | 431.661 ± 31.625 |
Pituitary | g | 0.012 ± 0.002 | 0.014 ± 0.002 | 0.014 ± 0.002 | 0.0142 ± 0.003 | 0.015 ± 0.002 | 0.015 ± 0.002 | 0.015 ± 0.002 | 0.016 ± 0.002 |
Pituitary/TBW | g/100 g | 0.004 ± 0.001 | 0.004 ± 0.000 | 0.004 ± 0.001 | 0.005 ± 0.001 * | 0.007 ± 0.001 | 0.007 ± 0.002 | 0.007 ± 0.001 | 0.008 ± 0.001 |
Pituitary/TBRW | g/100 g | 0.621 ± 0.094 | 0.720 ± 0.104 | 0.696 ± 0.106 | 0.730 ± 0.126 | 0.806 ± 0.107 | 0.812 ± 0.143 | 0.813 ± 0.122 | 0.875 ± 0.087 |
Spleen | g | 0.73 ± 0.13 | 0.78 ± 0.18 | 0.76 ± 0.12 | 0.70 ± 0.12 | 0.48 ± 0.12 | 0.47 ± 0.08 | 0.50 ± 0.09 | 0.46 ± 0.07 |
Spleen/TBW | g/100 g | 0.233 ± 0.035 | 0.241 ± 0.048 | 0.237 ± 0.026 | 0.223 ± 0.032 | 0.234 ± 0.046 | 0.229 ± 0.035 | 0.242 ± 0.043 | 0.221 ± 0.030 |
Spleen/TBRW | g/100 g | 38.648 ± 7.350 | 40.779 ± 9.099 | 38.966 ± 6.884 | 36.031 ± 5.488 | 25.898 ± 5.939 | 25.353 ± 4.689 | 26.979 ± 4.793 | 25.044 ± 3.166 |
Thymus | g | 0.672 ± 0.159 | 0.725 ± 0.156 | 0.711 ± 0.164 | 0.668 ± 0.119 | 0.542 ± 0.112 | 0.573 ± 0.115 | 0.526 ± 0.097 | 0.489 ± 0.084 |
Thymus/TBW | g/100 g | 0.215 ± 0.043 | 0.225 ± 0.042 | 0.223 ± 0.044 | 0.213 ± 0.028 | 0.264 ± 0.046 | 0.278 ± 0.052 | 0.253 ± 0.041 | 0.236 ± 0.047 |
Thymus/TBRW | g/100 g | 35.728 ± 8.575 | 37.924 ± 7.416 | 36.619 ± 8.324 | 34.506 ± 6.080 | 29.092 ± 5.263 | 30.818 ± 6.590 | 28.233 ± 4.811 | 26.699 ± 4.758 |
Thryoid + PTH | g | 0.015 ± 0.002 | 0.017 ± 0.003 | 0.017 ± 0.003 | 0.016 ± 0.003 | 0.015 ± 0.002 | 0.015 ± 0.002 | 0.013 ± 0.002 | 0.014 ± 0.002 |
Thryoid + PTH/TBW | g/100 g | 0.005 ± 0.001 | 0.006 ± 0.001 | 0.005 ± 0.001 | 0.005 ± 0.001 | 0.008 ± 0.001 | 0.007 ± 0.001 | 0.006 ± 0.001 * | 0.007 ± 0.001 |
Thryoid + PTH/TBRW | g/100 g | 0.805 ± 0.110 | 0.908 ± 0.157 | 0.887 ± 0.155 | 0.812 ± 0.136 | 0.822 ± 0.084 | 0.788 ± 0.112 | 0.722 ± 0.126 | 0.758 ± 0.090 |
Epididymides | g | 0.59 ± 0.06 | 0.62 ± 0.06 | 0.65 ± 0.04 | 0.62 ± 0.07 | ||||
Epididymides/TBW | g/100 g | 0.190 ± 0.019 | 0.194 ± 0.021 | 0.205 ± 0.023 | 0.201 ± 0.032 | ||||
Epididymides/TBRW | g/100 g | 31.294 ± 2.245 | 32.786 ± 3.976 | 33.387 ± 2.866 | 32.301 ± 4.294 | ||||
Sem Ves+Prostate | g | 1.76 ± 0.20 | 1.75 ± 0.21 | 1.88 ± 0.15 | 1.84 ± 0.22 | ||||
Sem Ves+ Prostate/TBW | g/100 g | 0.569 ± 0.083 | 0.543 ± 0.050 | 0.595 ± 0.071 | 0.593 ± 0.086 | ||||
Sem Ves+ Prostate/TBRW | g/100 g | 93.280 ± 10.280 | 91.923 ± 11.384 | 96.746 ± 6.438 | 95.193 ± 10.821 | ||||
Testes (g) | g | 2.84 ± 0.26 | 3.13 ± 0.27 * | 3.05 ± 0.18 | 2.92 ± 0.21 | ||||
Testes/TBW | g/100 g | 0.915 ± 0.076 | 0.977 ± 0.112 | 0.963 ± 0.070 | 0.937 ± 0.065 | ||||
Testes/TBRW | g/100 g | 150.543 ± 10.304 | 164.380 ± 13.689 * | 157.245 ± 11.300 | 151.047 ± 11.821 | ||||
Ovaries | g | 0.116 ± 0.019 | 0.127 ± 0.016 | 0.119 ± 0.014 | 0.123 ± 0.024 | ||||
Ovaries/TBW | g/100 g | 0.057 ± 0.007 | 0.062 ± 0.008 | 0.057 ± 0.007 | 0.059 ± 0.009 | ||||
Ovaries/TBRW | g/100 g | 6.274 ± 1.014 | 6.852 ± 1.064 | 6.398 ± 0.696 | 6.706 ± 1.153 | ||||
Uterus | g | 0.61 ± 0.16 | 0.49 ± 0.06 | 0.53 ± 0.22 | 0.54 ± 0.16 | ||||
Uterus/TBW | g/100 g | 0.299 ± 0.082 | 0.239 ± 0.038 | 0.254 ± 0.100 | 0.263 ± 0.089 | ||||
Uterus/TBRW | g/100 g | 32.838 ± 8.568 | 26.256 ± 3.783 | 28.250 ± 10.787 | 29.496 ± 8.388 |
Study Week | Severity Score | Nausea | Vomiting | Heartburn | Abdominal Bloating | Indigestion | Upper Abdominal Pain | Lower Abdominal Pain | Diarrhea | Constipation | Flatulence |
---|---|---|---|---|---|---|---|---|---|---|---|
1 (Placebo) | Mean (S.D.) | 6.0 (NA) n = 1 | 8.0 (NA) n = 1 | 2.0 (1.4) n = 2 | 3.9 (1.8) n = 11 | 1.0 (NA) n = 1 | 3.0 (NA) n = 1 | 3.5 (1.3) n = 4 | NA (NA) n = 0 | 3.8 (1.8) n = 14 | 2.7 (1.3) n = 36 |
2 | Mean (S.D.) | NA (NA) n = 0 | NA (NA) n = 0 | 1.0 (0.0) n = 2 | 3.4 (2.2) n = 9 | NA (NA) n = 0 | NA (NA) n = 0 | 2.4 (0.9) n = 5 | 6.0 (NA) n = 1 | 3.2 (1.2) n = 19 | 3.1 (1.7) n = 20 |
3 | Mean (S.D.) | 1.0 (0.0) n = 3 | NA (NA) n = 0 | NA (NA) n = 0 | 2.0 (1.0) n = 7 | 3.0 (NA) n = 1 | NA (NA) n = 0 | NA (NA) n = 0 | NA (NA) n = 0 | 2.2 (1.1) n = 19 | 2.4 (1.1) n = 17 |
4 | Mean (S.D.) | NA (NA) n = 0 | NA (NA) n = 0 | NA (NA) n = 0 | 2.3 (0.4) n = 7 | NA (NA) n = 0 | NA (NA) n = 0 | 3.3 (0.6) n = 3 | 1.0 (NA) n = 1 | 2.2 (0.8) n = 13 | 2.8 (1.5) n = 13 |
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Spears, J.L.; Kramer, R.; Nikiforov, A.I.; Rihner, M.O.; Lambert, E.A. Safety Assessment of Bacillus subtilis MB40 for Use in Foods and Dietary Supplements. Nutrients 2021, 13, 733. https://doi.org/10.3390/nu13030733
Spears JL, Kramer R, Nikiforov AI, Rihner MO, Lambert EA. Safety Assessment of Bacillus subtilis MB40 for Use in Foods and Dietary Supplements. Nutrients. 2021; 13(3):733. https://doi.org/10.3390/nu13030733
Chicago/Turabian StyleSpears, Jessica L., Richard Kramer, Andrey I. Nikiforov, Marisa O. Rihner, and Elizabeth A. Lambert. 2021. "Safety Assessment of Bacillus subtilis MB40 for Use in Foods and Dietary Supplements" Nutrients 13, no. 3: 733. https://doi.org/10.3390/nu13030733