1887

Abstract

Probiotics have been used for centuries in making fermented dairy products. The health benefits related to probiotics consumption are well recognized and they are generally regarded as safe (GRAS). Their therapeutic effects are due to the production of a variety of antimicrobial compounds, such as short-chain fatty acids, organic acids (such as lactic, acetic, formic, propionic and butyric acids), ethanol, hydrogen peroxide and bacteriocins. Ventilator-associated pneumonia (VAP) is a nosocomial infection associated with high mortality in intensive care units. VAP can result from endotracheal intubation and mechanical ventilation. These interventions increase the risk of infection as patients lose the natural barrier between the oropharynx and the trachea, which in turn facilitates the entry of pathogens through the aspiration of oropharyngeal secretions containing bacteria into the lung. In order to prevent this, probiotics have been used extensively against VAP. This review is an update containing information extracted from recent studies on the use of probiotics to treat VAP. In addition, probiotic safety, the therapeutic properties of probiotics, the probiotic strains used and the action of the probiotics mechanism are reviewed. Furthermore, the therapeutic effects of probiotic treatment procedures for VAP are compared to those of antibiotics. Finally, the influences of bacteriocin on the growth of human pathogens, and the side-effects and limitations of using probiotics for the treatment of VAP are addressed.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.000579
2017-09-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jmm/66/9/1275.html?itemId=/content/journal/jmm/10.1099/jmm.0.000579&mimeType=html&fmt=ahah

References

  1. Soccol CR, Vandenberghe L, Spier MR, Medeiros ABP, Yamaguishi CT et al. The potential of probiotics: a review. Food Technol Biotechnol 2010; 48:413–434
    [Google Scholar]
  2. Applegate JA, Fischer Walker CL, Ambikapathi R, Black RE. Systematic review of probiotics for the treatment of community-acquired acute diarrhea in children. BMC Public Health 2013; 13:1 [View Article][PubMed]
    [Google Scholar]
  3. Alfaleh K, Anabrees J. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Evid Based Child Health 2014; 9:584–671 [View Article][PubMed]
    [Google Scholar]
  4. Borchert D, Sheridan L, Papatsoris A, Faruquz Z, Barua JM et al. Prevention and treatment of urinary tract infection with probiotics: review and research perspective. Indian J Urol 2008; 24:139 [View Article][PubMed]
    [Google Scholar]
  5. Boyle RJ, Robins-Browne RM, Tang ML. Probiotic use in clinical practice: what are the risks?. Am J Clin Nutr 2006; 83:1256–1264[PubMed]
    [Google Scholar]
  6. Ashraf R, Shah NP. Antibiotic resistance of probiotic organisms and safety of probiotic dairy products. Int Food Res J 2011; 18:837–853
    [Google Scholar]
  7. File TM. Recommendations for treatment of hospital-acquired and ventilator-associated pneumonia: review of recent international guidelines. Clin Infect Dis 2010; 51:S42–S47 [View Article][PubMed]
    [Google Scholar]
  8. Kalanuria AA, Ziai W, Zai W, Mirski M. Ventilator-associated pneumonia in the ICU. Crit Care 2014; 18:208 [View Article][PubMed]
    [Google Scholar]
  9. Joseph NM, Sistla S, Dutta TK, Badhe AS, Parija SC. Ventilator-associated pneumonia: a review. Eur J Intern Med 2010; 21:360–368 [View Article][PubMed]
    [Google Scholar]
  10. Hunter JD. Ventilator associated pneumonia. BMJ 2012; 344:e3325 [View Article][PubMed]
    [Google Scholar]
  11. Morrow LE, Kollef MH, Casale TB. Probiotic prophylaxis of ventilator-associated pneumonia: a blinded, randomized, controlled trial. Am J Respir Crit Care Med 2010; 182:1058–1064 [View Article][PubMed]
    [Google Scholar]
  12. Banupriya B, Biswal N, Srinivasaraghavan R, Narayanan P, Mandal J. Probiotic prophylaxis to prevent ventilator associated pneumonia (VAP) in children on mechanical ventilation: an open-label randomized controlled trial. Intensive Care Med 2015; 41:677–685 [View Article][PubMed]
    [Google Scholar]
  13. Schultz MJ, Haas LE. Antibiotics or probiotics as preventive measures against ventilator-associated pneumonia: a literature review. Crit Care 2011; 15:R18 [View Article][PubMed]
    [Google Scholar]
  14. Pineiro M, Stanton C. Probiotic bacteria: legislative framework - requirements to evidence basis. J Nutr 2007; 137:850S–853[PubMed]
    [Google Scholar]
  15. Dobson A, Cotter PD, Ross RP, Hill C. Bacteriocin production: a probiotic trait?. Appl Environ Microbiol 2012; 78:1–6 [View Article][PubMed]
    [Google Scholar]
  16. Reis JA, Paula AT, Casarotti SN, Penna ALB. Lactic acid bacteria antimicrobial compounds: characteristics and applications. Food Eng Rev 2012; 4:124–140 [View Article]
    [Google Scholar]
  17. Ibrahem MD. Evolution of probiotics in aquatic world: potential effects, the current status in Egypt and recent prospectives. J Adv Res 2015; 6:765–791 [View Article][PubMed]
    [Google Scholar]
  18. Verna EC, Lucak S. Use of probiotics in gastrointestinal disorders: what to recommend?. Therap Adv Gastroenterol 2010; 3:307–319 [View Article]
    [Google Scholar]
  19. Huys G, Botteldoorn N, Delvigne F, de Vuyst L, Heyndrickx M et al. Microbial characterization of probiotics- advisory report of the Working Group "8651 Probiotics" of the Belgian Superior Health Council (SHC). Mol Nutr Food Res 2013; 57:1479–1504 [View Article][PubMed]
    [Google Scholar]
  20. Vandenplas Y, Huys G, Daube G. Probiotics: an update. J Pediatr (Rio J) 2015; 91:6–21 [View Article]
    [Google Scholar]
  21. Urben LM, Wiedmar J, Boettcher E, Cavallazzi R, Martindale RG et al. Bugs or drugs: are probiotics safe for use in the critically ill?. Curr Gastroenterol Rep 2014; 16:1–11 [View Article]
    [Google Scholar]
  22. Chi SY, Kim TO, Park CW, Yu JY, Lee B et al. Bacterial pathogens of ventilator associated pneumonia in a tertiary referral hospital. Tuberc Respir Dis 2012; 73:32–37 [View Article][PubMed]
    [Google Scholar]
  23. Trachoo N, Boudreaux C. Therapeutic properties of probiotic bacteria. J Biol Sci 2006; 6:202–208 [CrossRef]
    [Google Scholar]
  24. Anukam KC, Reid G. Probiotics: 100 years (1907–2007) after Elie Metchnikoff’s observation. Communicating Current Research and Educational Topics and Trends in Applied Microbiology 2007; 1:466–474
    [Google Scholar]
  25. de Oliveira Leite AM, Miguel MA, Peixoto RS, Rosado AS, Silva JT et al. Microbiological, technological and therapeutic properties of kefir: a natural probiotic beverage. Braz J Microbiol 2013; 44:341–349 [View Article][PubMed]
    [Google Scholar]
  26. Brown AC, Valiere A. Probiotics and medical nutrition therapy. Nutr Clin Care 2004; 7:56[PubMed]
    [Google Scholar]
  27. Behnsen J, Deriu E, Sassone-Corsi M, Raffatellu M. Probiotics: properties, examples, and specific applications. Cold Spring Harb Perspect Med 2013; 3:a010074 [View Article][PubMed]
    [Google Scholar]
  28. Isolauri E, Sütas Y, Kankaanpää P, Arvilommi H, Salminen S. Probiotics: effects on immunity. Am J Clin Nutr 2001; 73:444s–450[PubMed]
    [Google Scholar]
  29. Ashraf R, Shah NP. Immune system stimulation by probiotic microorganisms. Crit Rev Food Sci Nutr 2014; 54:938–956 [View Article][PubMed]
    [Google Scholar]
  30. Snydman DR. The safety of probiotics. Clin Infect Dis 2008; 46:S104–S111 [View Article][PubMed]
    [Google Scholar]
  31. American Thoracic SocietyInfectious Diseases Society of America Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171:388–416 [CrossRef]
    [Google Scholar]
  32. Charles MP, Kali A, Easow JM, Joseph NM, Ravishankar M et al. Ventilator-associated pneumonia. Australas Med J 2014; 7:334–344 [View Article][PubMed]
    [Google Scholar]
  33. Keyt H, Faverio P, Restrepo MI. Prevention of ventilator-associated pneumonia in the intensive care unit: a review of the clinically relevant recent advancements. Indian J Med Res 2014; 139:814[PubMed]
    [Google Scholar]
  34. Chastre J, Viau F, Brun P, Pierre J, Dauge MC et al. Prospective evaluation of the protected specimen brush for the diagnosis of pulmonary infections in ventilated patients. Am Rev Respir Dis 1984; 130:924–929 [View Article][PubMed]
    [Google Scholar]
  35. Fàbregas N, Ewig S, Torres A, El-Ebiary M, Ramirez J et al. Clinical diagnosis of ventilator associated pneumonia revisited: comparative validation using immediate post-mortem lung biopsies. Thorax 1999; 54:867–873 [View Article][PubMed]
    [Google Scholar]
  36. Wunderink RG, Woldenberg LS, Zeiss J, Day CM, Ciemins J et al. The radiologic diagnosis of autopsy-proven ventilator-associated pneumonia. Chest 1992; 101:458–463 [View Article][PubMed]
    [Google Scholar]
  37. Rea-Neto A, Youssef NC, Tuche F, Brunkhorst F, Ranieri VM et al. Diagnosis of ventilator-associated pneumonia: a systematic review of the literature. Crit Care 2008; 12:R56 [View Article][PubMed]
    [Google Scholar]
  38. Kollef MH. What is ventilator-associated pneumonia and why is it important?. Respir Care 2005; 50:714–724[PubMed]
    [Google Scholar]
  39. Isakow W, Morrow LE, Kollef MH. Probiotics for preventing and treating nosocomial infections: review of current evidence and recommendations. Chest 2007; 132:286–294 [View Article][PubMed]
    [Google Scholar]
  40. Mattar AF, Teitelbaum DH, Drongowski RA, Yongyi F, Harmon CM et al. Probiotics up-regulate MUC-2 mucin gene expression in a Caco-2 cell-culture model. Pediatr Surg Int 2002; 18:586–590 [View Article][PubMed]
    [Google Scholar]
  41. Mack DR, Ahrne S, Hyde L, Wei S, Hollingsworth MA. Extracellular MUC3 mucin secretion follows adherence of Lactobacillus strains to intestinal epithelial cells in vitro. Gut 2003; 52:827–833 [View Article][PubMed]
    [Google Scholar]
  42. Kelsall BL. Innate and adaptive mechanisms to control [corrected] pathological intestinal inflammation. J Pathol 2008; 214:242–259 [View Article][PubMed]
    [Google Scholar]
  43. Möndel M, Schroeder BO, Zimmermann K, Huber H, Nuding S et al. Probiotic E. coli treatment mediates antimicrobial human β-defensin synthesis and fecal excretion in humans. Mucosal Immunol 2009; 2:166–172 [View Article][PubMed]
    [Google Scholar]
  44. Ogawa M, Shimizu K, Nomoto K, Tanaka R, Hamabata T et al. Inhibition of in vitro growth of Shiga toxin-producing Escherichia coli O157:H7 by probiotic Lactobacillus strains due to production of lactic acid. Int J Food Microbiol 2001; 68:135–140 [View Article][PubMed]
    [Google Scholar]
  45. Wang J, Liu KX, Ariani F, Tao LL, Zhang J et al. Probiotics for preventing ventilator-associated pneumonia: a systematic review and meta-analysis of high-quality randomized controlled trials. PLoS One 2013; 8:e83934 [View Article][PubMed]
    [Google Scholar]
  46. Bo L, Li J, Tao T, Bai Y, Ye X et al. Probiotics for preventing ventilator-associated pneumonia. Cochrane Database Syst Rev 2014; 10:CD009066 [View Article][PubMed]
    [Google Scholar]
  47. Liu KX, Zhu YG, Zhang J, Tao LL, Lee JW et al. Probiotics' effects on the incidence of nosocomial pneumonia in critically ill patients: a systematic review and meta-analysis. Crit Care 2012; 16:R109 [View Article][PubMed]
    [Google Scholar]
  48. Glück U, Gebbers JO. Ingested probiotics reduce nasal colonization with pathogenic bacteria (Staphylococcus aureus, Streptococcus pneumoniae, and β-hemolytic streptococci). Am J Clin Nutr 2003; 77:517–520[PubMed]
    [Google Scholar]
  49. Klarin B, Molin G, Jeppsson B, Larsson A. Use of the probiotic Lactobacillus plantarum 299 to reduce pathogenic bacteria in the oropharynx of intubated patients: a randomised controlled open pilot study. Crit Care 2008; 12:R136 [View Article][PubMed]
    [Google Scholar]
  50. Knight DJ, Gardiner D, Banks A, Snape SE, Weston VC et al. Effect of synbiotic therapy on the incidence of ventilator associated pneumonia in critically ill patients: a randomised, double-blind, placebo-controlled trial. Intensive Care Med 2009; 35:854–861 [View Article][PubMed]
    [Google Scholar]
  51. Forestier C, Guelon D, Cluytens V, Gillart T, Sirot J et al. Oral probiotic and prevention of Pseudomonas aeruginosa infections: a randomized, double-blind, placebo-controlled pilot study in intensive care unit patients. Crit Care 2008; 12:R69 [View Article][PubMed]
    [Google Scholar]
  52. Siempos II, Ntaidou TK, Falagas ME. Impact of the administration of probiotics on the incidence of ventilator-associated pneumonia: a meta-analysis of randomized controlled trials. Crit Care Med 2010; 38:954–962 [View Article][PubMed]
    [Google Scholar]
  53. Petrof EO, Dhaliwal R, Manzanares W, Johnstone J, Cook D et al. Probiotics in the critically ill: a systematic review of the randomized trial evidence. Crit Care Med 2012; 40:3290–3302 [View Article][PubMed]
    [Google Scholar]
  54. Johnston BC, Goldenberg JZ, Vandvik PO, Sun X, Guyatt GH. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev 2011; 11:CD004827 [View Article][PubMed]
    [Google Scholar]
  55. Kelesidis T, Pothoulakis C. Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders. Therap Adv Gastroenterol 2012; 5:111–125 [View Article][PubMed]
    [Google Scholar]
  56. Valdéz JC, Peral MC, Rachid M, Santana M, Perdigón G. Interference of Lactobacillus plantarum with Pseudomonas aeruginosa in vitro and in infected burns: the potential use of probiotics in wound treatment. Clin Microbiol Infect 2005; 11:472–479 [View Article][PubMed]
    [Google Scholar]
  57. Plantinga NL, Bonten MJM. Selective decontamination and antibiotic resistance in ICUs. Crit Care 2015; 19:1–7 [View Article]
    [Google Scholar]
  58. Schnabel RM, Scholte JB, van der Velden KE, Roekaerts PM, Bergmans DC. Ventilator-associated pneumonia rates after introducing selective digestive tract decontamination. Infect Dis 2015; 47:650–653 [View Article][PubMed]
    [Google Scholar]
  59. Sánchez García M, Cambronero Galache JA, López Diaz J, Cerdá Cerdá E, Rubio Blasco J et al. Effectiveness and cost of selective decontamination of the digestive tract in critically ill intubated patients. A randomized, double-blind, placebo-controlled, multicenter trial. Am J Respir Crit Care Med 1998; 158:908–916 [View Article][PubMed]
    [Google Scholar]
  60. Krueger WA, Lenhart FP, Neeser G, Ruckdeschel G, Schreckhase H et al. Influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections, organ dysfunctions, and mortality in critically ill surgical patients: a prospective, stratified, randomized, double-blind, placebo-controlled clinical trial. Am J Respir Crit Care Med 2002; 166:1029–1037 [View Article][PubMed]
    [Google Scholar]
  61. de Smet AM, Kluytmans JA, Blok HE, Mascini EM, Benus RF et al. Selective digestive tract decontamination and selective oropharyngeal decontamination and antibiotic resistance in patients in intensive-care units: an open-label, clustered group-randomised, crossover study. Lancet Infect Dis 2011; 11:372–380 [View Article][PubMed]
    [Google Scholar]
  62. Oostdijk EA, de Smet AM, Blok HE, Thieme Groen ES, van Asselt GJ et al. Ecological effects of selective decontamination on resistant gram-negative bacterial colonization. Am J Respir Crit Care Med 2010; 181:452–457 [View Article][PubMed]
    [Google Scholar]
  63. Oudhuis GJ, Bergmans DC, Dormans T, Zwaveling JH, Kessels A et al. Probiotics versus antibiotic decontamination of the digestive tract: infection and mortality. Intensive Care Med 2011; 37:110–117 [View Article][PubMed]
    [Google Scholar]
  64. Barraud D, Blard C, Hein F, Marçon O, Cravoisy A et al. Probiotics in the critically ill patient: a double blind, randomized, placebo-controlled trial. Intensive Care Med 2010; 36:1540–1547 [View Article][PubMed]
    [Google Scholar]
  65. Cannon JP, Lee TA, Bolanos JT, Danziger LH. Pathogenic relevance of Lactobacillus: a retrospective review of over 200 cases. Eur J Clin Microbiol Infect Dis 2005; 24:31–40 [View Article][PubMed]
    [Google Scholar]
  66. Besselink MGH, Timmerman HM, Buskens E, Nieuwenhuijs VB, Akkermans LMA et al. Probiotic prophylaxis in patients with predicted severe acute pancreatitis (PROPATRIA): design and rationale of a double-blind, placebo-controlled randomised multicenter trial [ISRCTN38327949]. BMC Surg 2004; 4:1 [View Article]
    [Google Scholar]
  67. Crooks NH, Snaith C, Webster D, Gao F, Hawkey P. Clinical review: probiotics in critical care. Crit Care 2012; 16:237 [View Article]
    [Google Scholar]
  68. Santagati M, Scillato M, Patanè F, Aiello C, Stefani S. Bacteriocin-producing oral streptococci and inhibition of respiratory pathogens. FEMS Immunol Med Microbiol 2012; 65:23–31 [View Article][PubMed]
    [Google Scholar]
  69. Fiedler T, Riani C, Koczan D, Standar K, Kreikemeyer B et al. Protective mechanisms of respiratory tract Streptococci against Streptococcus pyogenes biofilm formation and epithelial cell infection. Appl Environ Microbiol 2013; 79:1265–1276 [View Article][PubMed]
    [Google Scholar]
  70. Gillor O, Etzion A, Riley MA. The dual role of bacteriocins as anti- and probiotics. Appl Microbiol Biotechnol 2008; 81:591–606 [View Article][PubMed]
    [Google Scholar]
  71. Sogabe-Ashigaki K, Imai S, Okada A, Matin K, Akimaru G et al. Effects of Lactobacillus crispatus as a candidate for oral probiotic bacteria on Haemophilus influenzae. Asian Pac J Dent 2015; 15:3–11
    [Google Scholar]
  72. Adebayo F, Afolabi OR, Akintokun AK. Antimicrobial Properties of Purified Bacteriocins Produced from Lactobacillus casei and Lactobacillus fermentum against Selected Pathogenic Microorganisms. Br J Med Med Res 2014; 4:3415–3431 [View Article]
    [Google Scholar]
  73. Sanders ME, Gibson GR, Gill HS, Guarner F. Probiotics: their potential to impact human health. Council for Agricultural Science and Technology Issue Paper 2007; 36:1–20
    [Google Scholar]
  74. Ohashi Y, Ushida K. Health-beneficial effects of probiotics: Its mode of action. Anim Sci J 2009; 80:361–371 [View Article][PubMed]
    [Google Scholar]
  75. Woo PC, Fung AM, Lau SK, Yuen KY. Identification by 16S rRNA gene sequencing of Lactobacillus salivarius bacteremic cholecystitis. J Clin Microbiol 2002; 40:265–267 [View Article][PubMed]
    [Google Scholar]
  76. Duprey KM, Mccrea L, Rabinowitch BL, Azad KN. Pyelonephritis and bacteremia from Lactobacillus delbrueckii. Case Rep Infect Dis 2012; 2012:1–3 [View Article][PubMed]
    [Google Scholar]
  77. Zé-Zé L, Tenreiro R, Duarte A, Salgado MJ, Melo-Cristino J et al. Case of aortic endocarditis caused by Lactobacillus casei. J Med Microbiol 2004; 53:451–453 [View Article][PubMed]
    [Google Scholar]
  78. Mackay AD, Taylor MB, Kibbler CC, Hamilton-Miller JM. Lactobacillus endocarditis caused by a probiotic organism. Clin Microbiol Infect 1999; 5:290–292 [View Article][PubMed]
    [Google Scholar]
  79. Tommasi C, Equitani F, Masala M, Ballardini M, Favaro M et al. Diagnostic difficulties of Lactobacillus casei bacteraemia in immunocompetent patients: a case report. J Med Case Rep 2008; 2:315 [View Article][PubMed]
    [Google Scholar]
  80. Russo A, Angeletti S, Lorino G, Venditti C, Falcone M et al. A case of Lactobacillus casei bacteraemia associated with aortic dissection: is there a link?. New Microbiol 2010; 33:175[PubMed]
    [Google Scholar]
  81. Salminen MK, Rautelin H, Tynkkynen S, Poussa T, Saxelin M et al. Lactobacillus bacteremia, clinical significance, and patient outcome, with special focus on probiotic L. rhamnosus GG. Clin Infect Dis 2004; 38:62–69 [View Article][PubMed]
    [Google Scholar]
  82. Rasul S, Farhat F, Ramsahai S, Delapenha R, Shah N. Pyelonephritis and bacteremia from Lactobacillus acidophilus. J Med Cases 2012; 3:223–225
    [Google Scholar]
  83. Bagwan N, Bhanot N. Bacteremia Secondary to Bifidobacterium Longum: A Rare Entity. Infect Dis Clin Pract 2014; 22:e100e102
    [Google Scholar]
  84. Weber E, Reynaud Q, Suy F, Gagneux-Brunon A, Carricajo A et al. Bifidobacterium species bacteremia: risk factors in adults and infants. Clin Infect Dis 2015; 61:482–484 [View Article][PubMed]
    [Google Scholar]
  85. Cassone M, Serra P, Mondello F, Girolamo A, Scafetti S et al. Outbreak of Saccharomyces cerevisiae subtype boulardii fungemia in patients neighboring those treated with a probiotic preparation of the organism. J Clin Microbiol 2003; 41:5340–5343 [View Article][PubMed]
    [Google Scholar]
  86. Herbrecht R, Nivoix Y. Saccharomyces cerevisiae fungemia: an adverse effect of Saccharomyces boulardii probiotic administration. Clin Infect Dis 2005; 40:1635–1637 [View Article][PubMed]
    [Google Scholar]
  87. Thygesen JB, Glerup H, Tarp B. Saccharomyces boulardii fungemia caused by treatment with a probioticum. BMJ Case Rep 2012; 2012:bcr0620114412 [View Article][PubMed]
    [Google Scholar]
  88. Wong A, Ngu DY, Dan LA, Ooi A, Lim RL. Detection of antibiotic resistance in probiotics of dietary supplements. Nutr J 2015; 14:1 [View Article][PubMed]
    [Google Scholar]
  89. Gueimonde M, Sánchez B, G de Los Reyes-Gavilán C, Margolles A. Antibiotic resistance in probiotic bacteria. Front Microbiol 2013; 4:1–6 [View Article][PubMed]
    [Google Scholar]
  90. Sharma P, Tomar SK, Goswami P, Sangwan V, Singh R. Antibiotic resistance among commercially available probiotics. Food Res Int 2014; 57:176–195 [View Article]
    [Google Scholar]
  91. Simkins J, Kaltsas A, Currie BP. Investigation of inpatient probiotic use at an academic medical center. Int J Infect Dis 2013; 17:e321e324 [View Article][PubMed]
    [Google Scholar]
  92. Heineman J, Bubenik S, Mcclave S, Martindale R. Fighting fire with fire: is it time to use probiotics to manage pathogenic bacterial diseases?. Curr Gastroenterol Rep 2012; 14:343–348 [View Article][PubMed]
    [Google Scholar]
  93. Ishibashi N, Yamazaki S. Probiotics and safety. Am J Clin Nutr 2001; 73:465s–470[PubMed]
    [Google Scholar]
  94. Urben LM, Wiedmar J, Boettcher E, Cavallazzi R, Martindale RG et al. Bugs or drugs: are probiotics safe for use in the critically ill Current gastroenterology reports; 2014; 161–11
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.000579
Loading
/content/journal/jmm/10.1099/jmm.0.000579
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error