Prevention of Recurrent Acute Otitis Media in Children Through the Use of Lactobacillus salivarius PS7, a Target-Specific Probiotic Strain
Abstract
:1. Introduction
2. Materials and Methods
2.1. Isolation and Identification of the Strain
2.2. Survival after In Vitro Exposure to Saliva and Gastrointestinal-Like Conditions
2.3. Adhesion to Caco-2/HT-29 Cells
2.4. Production of Riboflavin, Folate and Cyanocobalamin
2.5. Antimicrobial Activity of Strain PS7 against AOM-Related Pathogens
2.6. Production of Specific Antimicrobials (Bacteriocins, Lactic Acid, Acetic Acid, Hydrogen Peroxide) by Strain PS7
2.7. Coagregation Assays
2.8. Co-Culture Studies
2.9. Sensitivity to Antibiotics
2.10. Formation of Biogenic Amines and Degradation of Mucin
2.11. Acute and Repeated Dose (4-Weeks) Oral Toxicity Studies in a Rat Model
2.12. Pilot Clinical Trial: Prevention of rAOM in Children
2.13. Statistical Analysis
3. Results
3.1. Identification and In Vitro Characterization of the Strain
3.2. Acute and Repeated Dose (4-Weeks) oral Toxicity Studies in a Rat Model
3.3. Pilot Clinical Trial: Prevention of AOM in Children
4. Discussion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Indicator Strain | Overlay Method (cm) | Well Diffusion Assay (cm) | Co-Cultures (CFU/mL) | ||
---|---|---|---|---|---|
Non-Adjusted pH | pH 6.2 | Initial Load | Final Load | ||
S. pneumoniae MP07 | 3.6 | 1.1 | 1.1 | 7.40 | Nd a |
S. pyogenes MP03 | 2.0 | 1.2 | 0.7 | 7.74 | Nd a |
S. aureus MP29 | 1.6 | 1.3 | 1.2 | 7.52 | 4.81 a |
S. epidermidis MP33 | 2.3 | 1.1 | 1.0 | 7.53 | 5.90 a |
A. otitidis MP02 | 1.0 | 1.2 | 1.2 | – | – |
E. faecalis MP64 | 0.5 | 0.4 | 0.4 | 8.02 | 8.78 b |
H. influenzae MP04 | 2.2 | – | – | – | – |
M. catarrhalis MP08 | 2.1 | – | – | – | – |
P. aeruginosa MP24 | 1.5 | – | – | – | – |
E. coli MP69 | 1.4 | – | – | 7.70 | 5.74 a |
pH | L–Lactic Acid | D-Lactic Acid | Acetic Acid |
---|---|---|---|
4.01± 0.04 | 10.29 ± 0.70 | Nd | 0.68 ± 0.17 |
Antibiotics | Cut-Off Values * | MIC (L. salivarius PS7) |
---|---|---|
Ampicillin | 4 | 0.5 |
Clindamycin | 4 | 0.5 |
Chloramphenicol | 4 | 2 |
Erythromycin | 1 | 0.25 |
Streptomycin | 64 | 32 |
Gentamicin | 16 | 2 |
Kanamycin | 64 | 128 |
Tetracyclin | 8 | 2 |
Vancomycin | n.r. | >128 |
Linezolid | 2 | 1 |
Penicillin | 1 | 0.25 |
Characteristic | Sex | n | Mean ± SD or Median * | p-Value |
---|---|---|---|---|
Age (Years) and Gender | 3.31 ± 1.7 | |||
<3 years (n = 30) | Males | 16 | ||
Females | 14 | |||
≥3 years (n = 31) | Males | 15 | ||
Females | 16 | |||
Inclusion months: | ||||
September | 7 | |||
October | 5 | |||
November | 6 | |||
December | 7 | |||
January | 6 | |||
February | 10 | |||
March | 9 | |||
April | 6 | |||
May | 3 | |||
June | 2 | |||
History of AOM episodes/child | ||||
Preceding 6 months | 4 (3–4) * | <0.001 ¥ | ||
Preceding 12 months | 5 (5–6) * | <0.001 ¥ | ||
During the study | 0 (0–1) * |
Time 0 | After 6 Months | p-Value | |
---|---|---|---|
Number of positive samples (bacterial growth) | 61 | 17 | < 0.001 ¥ |
Median log10 CFU (per swab) | 4 (3.5–5) | 2 (1.5–2) | 0.012 * |
Number of samples with the presence of: | |||
Actinomyces europaeus | 2 | 0 | |
Alloiococcus otitidis | 12 | 2 | |
Coagulase-negative staphylococci | 14 | 15 | |
Haemophilus haemolyticus | 11 | 1 | |
Haemophilus influenza | 7 | 1 | |
Moraxella catharralis | 14 | 3 | |
Neisseria spp. | 6 | 0 | |
Pseudomonas aeruginosa | 4 | 0 | |
Rhodococcus ruber | 2 | 0 | |
Staphylococcus aureus | 11 | 3 | |
Streptococcus pneumoniae | 9 | 3 | |
Streptococcus pyogenes | 10 | 6 | |
Group viridans streptococci | 9 | 11 |
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Cárdenas, N.; Martín, V.; Arroyo, R.; López, M.; Carrera, M.; Badiola, C.; Jiménez, E.; Rodríguez, J.M. Prevention of Recurrent Acute Otitis Media in Children Through the Use of Lactobacillus salivarius PS7, a Target-Specific Probiotic Strain. Nutrients 2019, 11, 376. https://doi.org/10.3390/nu11020376
Cárdenas N, Martín V, Arroyo R, López M, Carrera M, Badiola C, Jiménez E, Rodríguez JM. Prevention of Recurrent Acute Otitis Media in Children Through the Use of Lactobacillus salivarius PS7, a Target-Specific Probiotic Strain. Nutrients. 2019; 11(2):376. https://doi.org/10.3390/nu11020376
Chicago/Turabian StyleCárdenas, Nivia, Virginia Martín, Rebeca Arroyo, Mario López, Marta Carrera, Carlos Badiola, Esther Jiménez, and Juan M. Rodríguez. 2019. "Prevention of Recurrent Acute Otitis Media in Children Through the Use of Lactobacillus salivarius PS7, a Target-Specific Probiotic Strain" Nutrients 11, no. 2: 376. https://doi.org/10.3390/nu11020376