Skip to main content

Advertisement

SpringerLink
Log in

Probiotic Formulations: Application and Status as Pharmaceuticals—A Review

  • Published:
Probiotics and Antimicrobial Proteins Aims and scope Submit manuscript

Abstract

The use of probiotics is a new way to control and treat infections in this modern era. Application of beneficial bacteria to protect against detrimental bacteria in the gastrointestinal tract and thus reap a positive health benefit is the basis of probiotic therapy. Probiotics have a long global history of traditional use. They are normally consumed through fermented foods and are currently sold mostly as ingredients in foods or nutritional supplements. They are also supplied as pharma products. Recent research has highlighted the probiotic potential in the treatment or prevention of disease conditions, maintenance of health, improving immunity and in the reduction in the risk of future diseases. But their position in the pharmaceutical industry is still not very clear. Clinical practitioners use probiotic pharma products mostly as supplements. Their status as drugs is still unclear. This review is aimed to analyze probiotics as pharmaceuticals, their current status as dietary supplements and drugs, existing probiotic preparations and future research needs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Elmer GW (2001) Probiotics: ‘living drugs’. Am J Health-Syst Pharm 58(12):1101–1109

    CAS  Google Scholar 

  2. Kaur IP, Chopra K, Saini A (2002) Probiotics: potential pharmaceutical applications. Eur J Pharm Sci 15:1–9

    Article  CAS  Google Scholar 

  3. Sanders ME (2003) Probiotics: considerations for human health. Nutr Rev 61(3):91–99

    Article  Google Scholar 

  4. Lemberg DA, Ooi CY, Day AS (2007) Probiotics in paediatric gastrointestinal diseases- Review. J Paediatr Child Health 43:331–336

    Article  Google Scholar 

  5. Fuller R (1991) Probiotics in human medicine. Gut 32:439–442

    Article  CAS  Google Scholar 

  6. Sleator RD (2010) Probiotic therapy—recruiting old friends to fight new foes. Gut Pathog 2:51–54

    Google Scholar 

  7. Raja BR, Arunachalam KD (2011) Market potential for probiotic nutritional supplements in India. AJBM 5(14):5418–5423

    Google Scholar 

  8. Dubey AP, Rajeshwari K, Chakravarty A, Famularo G (2008) Use of VSL[#]3 in the treatment of rotavirus diarrhea in children: preliminary results. J Clin Gastroenterol 42(Suppl 3 Pt 1):S126–S129

    Article  Google Scholar 

  9. McFarland LV (2007) Meta-analysis of probiotics for the prevention of traveler’s diarrhea. Travel Med Infect Dis 5:97–105

    Article  Google Scholar 

  10. Saavedra JM (2001) Clinical applications of probiotic agents. Am J Clin Nutr 73(suppl):1147S–1151S

    CAS  Google Scholar 

  11. Salminen S (2001) Human studies on probiotics: aspects of scientific documentation–review. Scand J Nutr 45:8–12

    Google Scholar 

  12. Hempel S, Newberry SJ, Maher AR, Wang Z, Miles JN, Shanman R, Johnsen B, Shekelle PG (2012) Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA 307(18):1959–1969

    Article  CAS  Google Scholar 

  13. Culligan EP, Hill C, Sleator RD (2009) Probiotics and gastrointestinal disease: successes, problems and future prospects-review. Gut Pathog 1(19):1–12

    Google Scholar 

  14. Gill HS, Guarner F (2004) Probiotics and human health: a clinical perspective. Postgrad Med J 80:516–526

    Article  CAS  Google Scholar 

  15. Barrons R, Tassone D (2008) Use of lactobacillus probiotics for bacterial genitourinary infections in women: a Review. Clin Ther 30:453–468

    Article  CAS  Google Scholar 

  16. Parvez S, Malik KA, Ah Kang S, Kim HY (2006) Probiotics and their fermented food products are beneficial for health. J Appl Microbiol 100:1171–1185

    Article  CAS  Google Scholar 

  17. Pantoflickova DL, Theulaz IC, Blum AL (2007) Helicobacter pylori and Probiotics. J Nutr 812S–818S

  18. Bhattacharyya BK (2009) Emergence of probiotics in therapeutic applications. Int J Pharm Sci Nanotechol 2:383–389

    Google Scholar 

  19. Marteau P, Shanahan F (2003) Basic aspects and pharmacology of probiotics: an overview of pharmacokinetics, mechanisms of action and side-effects. Best Pract Res Clin Gastroenterol 17:725–740

    Article  CAS  Google Scholar 

  20. FAO/WHO (2002) Guidelines for the evaluation of probiotics in food. http://www.who.int/foodsafety/fs_management/en/probiotic_ guidelines

  21. Osvath R (2000) FDA food advisory committee to discuss criteria for safety of probiotics. Food Chem News 42:12

    Google Scholar 

  22. Isolauri E, Arvola T, Sutas Y, Moilanen E, Salminen S (2000) Probiotics in the management of atopic eczema. Clin Exp Allergy 30:1604–1610

    Article  CAS  Google Scholar 

  23. Schiffrin EJ, Brassart D, Servin AL, Rochat F, Donnet-Hughes A (1997) Immune modulation of blood leukocytes in humans by lactic acid bacteria: criteria for strain selection. Am J Clin Nutr 66(2):515S–520S

    CAS  Google Scholar 

  24. Chouraqui JP, Van Egroo LD, Fichot MC (2004) Acidified milk formula supplemented with Bifidobacterium lactis: impact on infant diarrhea in residential care settings. J Pediatr Gastroenterol Nutr 38:288–292

    Article  Google Scholar 

  25. Marteau P, de Vrese M, Cellier C, Schrezenmeir J (2001) Protection from gastrointestinal diseases with the use of probiotics. Am J Clin Nutr 73:430S–436S

    CAS  Google Scholar 

  26. Shioya M, Nakaoka K, Igarashi R, Iizuka N, Abe T, Benno Y (2000) Effect of fermented milk containing Bifidobacterium lactis FK 120 on the fecal flora and fecal properties in healthy female volunteers. Food Health and Nutrition Research. J Nutr Fd 3:7–18

    Google Scholar 

  27. de Vrese M, Rautenberg P, Laue C, Koopmans M, Herremans T, Schrezenmeir J (2005) Probiotic bacteria stimulate virus-specific neutralizing antibodies following a booster polio vaccination. Eur J Nutr 44:406–413

    Article  Google Scholar 

  28. Gaon D, Garcia H, Winter L, Rodriguez N, Quintasi R, Gonzalez SN, Oliver G (2003) Effect of Lactobacillus strains and Saccharomyces boulardii on persistent diarrhea in children. Medicina 63:293–298

    Google Scholar 

  29. Saavedra JM, Abi-Hanna A, Moore N, Yolken RH (2004) Long-term consumption of infant formulas containing live probiotic bacteria: tolerance and safety. Am J Clin Nutr 79:261–267

    CAS  Google Scholar 

  30. Saavedra JM, Bauman NA, Oung I, Perman JA, Yolken RH (1994) Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for prevention of diarrhea and shedding of rotavirus. Lancet 344:1046–1049

    Article  CAS  Google Scholar 

  31. Sullivan Å, Bennet R, Viitanen M, Palmgren AC, Nord CE (2002) Influence of Lactobacillus F19 on intestinal microflora in children and elderly persons and impact on Helicobacter pylori infections. Microbial Ecol Health Dis Suppl 3:17–21

    Article  Google Scholar 

  32. Cox AJ, Pyne DB, Saunders PU, Fricker PA (2010) Oral administration of the probiotic Lactobacillus fermentum VRI-003 and mucosal immunity in endurance athletes. Br J Sports Med 44:222–226

    Article  CAS  Google Scholar 

  33. French PW, Penny R (2009) Use of probiotic bacteria as an adjuvant for an influenza vaccine. Int J Probiotics Prebiotics 4(3):175–180

    Google Scholar 

  34. Ringel-Kulka T, Palsson OS, Maier D et al (2011) Probiotic bacteria Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 versus placebo for the symptoms of bloating in patients with functional bowel disorders: a double-blind study. J Clin Gastroenterol 45(6):518–525

    Article  Google Scholar 

  35. Hojsak I, Snovak N, Abdovic S, Szajewska H, Misak Z, Kolacek S (2010) Lactobacillus GG in the prevention of gastrointestinal and respiratory tract infections in children who attend day care centers: a randomized, double-blind, placebo-controlled trial. Clin Nutr 29(3):312–316

    Article  Google Scholar 

  36. Isolauri E, Juntunen M, Rautanen T, Sillanaukee P, Koivula T (1991) A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children. Pediatrics 88:90–97

    CAS  Google Scholar 

  37. Heyman M, Ménard S (2002) Probiotic microorganisms: how they affect intestinal Pathophysiology. CMLS 59:001–15

    Article  Google Scholar 

  38. Shimauchi H, Mayanagi G, Nakaya S et al (2008) Improvement of periodontal condition by probiotics with Lactobacillus salivarius WB21: a randomized, double-blind, placebo-controlled study. J Clin Periodontol 35:897–905

    Article  CAS  Google Scholar 

  39. Hoffman FA (2008) Development of probiotics as biologic drugs. Clin Infect Dis 46(Suppl 2):S125–S127

    Article  Google Scholar 

  40. Ross J (2006) Regulatory considerations. In american society for microbiology colloquium report probiotic microbes: the scientific basis. American Academy of Microbiology, Washington, p 8

    Google Scholar 

  41. Vaillancourt J (2006) Regulating Pre-and Pro-biotics: A US FDA Perspective. In Institute of medicine report of the forum on microbial threats workshop summary. Ending the war metaphor: the future agenda for unraveling the host-microbe relationship. National Academies Press, Washington, pp 229–237

    Google Scholar 

  42. Gibson GR, Brummer RJ, Isolauri E, Lochs H, Morelli L, Ockhuizen T, Rowland IR, Schrezenmeir J, Stanton C, Verbeke K (2011) The design of probiotic studies to substantiate health claims. Gut Microbes 2(5):299–305

    Article  Google Scholar 

  43. Mercenier A, Pavan S, Pot B (2002) Probiotics as biotherapeutic agents: present knowledge and future prospects. Curr Pharm Des 8:99–110

    Article  Google Scholar 

  44. Saxelin M (2008) Probiotic formulations and applications, the current probiotics market, and changes in the marketplace: a European perspective. Clin Infect Dis 46:S76–S79

    Article  Google Scholar 

  45. ICMR-DBT (2011) Guidelines for evaluation of probiotics in food. Director General, Indian Council of Medical Research, New Delhi-110 029

  46. Food Safety and Standards Act of India (2006) Ministry of health and family welfare. New Delhi, Government of India

    Google Scholar 

  47. Czinn SJ, Blanchard SS (2009) Probiotics in foods and supplements. In: Michail S, Sherman PM (eds) Nutrition and health: probiotics in Pediatric Medicine, © Humana Press. NJ, Totowa, pp 299–306

    Chapter  Google Scholar 

  48. Bora PS, Puri V, Bansal AK (2009) Physicochemical properties and excipient compatibility studies of probiotic Bacillus coagulans spores. Sci Pharm 77:625–637

    Article  CAS  Google Scholar 

  49. Yang L, Chu JS, Fix JA (2002) Colon-specific drug delivery: new approaches and in vitro/in vivo evaluation. Int J Pharm 235:1–15

    Article  CAS  Google Scholar 

  50. Prakash S, Urbanska AM (2008) Colon-targeted delivery of live bacterial cell biotherapeutics including microencapsulated live bacterial cells- Review. Biolog Targets Ther 2(3):355–378

    Article  CAS  Google Scholar 

  51. Mombelli B, Gismondo MR (2000) The use of probiotics in medical practice. Int J Antimicrobial Agents 16:531–536

    Article  CAS  Google Scholar 

  52. Forum Pharmacopeial (2007) Proposed New USP General Information Chapter. Excipient Performance 33(6):1311–1323

    Google Scholar 

  53. http://www.daniscosupplements.com

  54. Tursi A, Brandimarte G, Papa A et al (2010) Treatment of relapsing mild-to-moderate Ulcerative Colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: a Double-Blind, Randomized, Placebo-Controlled Study. Am J Gastroenterol 105:2218–2227

    Article  Google Scholar 

  55. Kim HJ, Camilleri M, McKinzie S et al (2003) A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 17:895–904

    Article  CAS  Google Scholar 

  56. Kim HJ, Vazquez Roque MI, Camilleri M et al (2005) A randomized controlled trial of a probiotic combination VSL# 3 and placebo in irritable bowel syndrome with bloating. Neurogastroenterol Motil 17:687–696

    Article  CAS  Google Scholar 

  57. Andresen V, Baumgart DC (2006) Role of probiotics in the treatment of irritable bowel syndrome: potential mechanisms and current clinical evidence. Int J Probiotics Prebiotics 1:11–18

    Google Scholar 

  58. Taipale T, Pienihäkkinen K, Isolauri E et al (2010) Bifidobacterium animalis subsp. lactis BB-12® in reducing the risk of infections in infancy. British. J Nutr 105(3):409–416

    Article  Google Scholar 

  59. Rizzardini G, Eskesen D, Calder PC, Capetti A, Jespersen L, Clerici M (2011) Evaluation of the immune benefits of two probiotic strains Bifidobacterium animalis ssp. lactis, BB-12w and Lactobacillus paracasei ssp. paracasei, L. casei 431w in an influenza vaccination model: a randomised, double-blind, placebo-controlled study. British J Nutr 1–9

  60. West NP, Pyne DB, Cripps AW et al (2011) Lactobacillus fermentum (PCC®) supplementation and gastrointestinal and respiratory-tract illness symptoms: a randomised control trial in athletes. Nutr J 10:1–11

    Article  Google Scholar 

  61. Szajewska H, Kotowska M, Mrukowicz JZ, Armanska M, Mikolajezyk W (2001) Efficacy of Lactobacillus sp strain GG in prevention of nosocominal diarrhea in infants. J Pediatr Gastroenterol Nutr 138:361–365

    CAS  Google Scholar 

  62. Bhalla A(2011) Randomized, placebo-controlled, double-blind, multicentric trial on efficacy and safety of Providac techsules (Lactobacillus acidophilus LA-5® and Bifidobacterium BB-12®) for prevention of antibiotic-associated diarrhea in Indian patients. J Clin Pharmacol 51:1327

    Google Scholar 

  63. Sheu BS, Wu JJ, Lo CY (2002) Impact of supplement with Lactobacillus—and Bifidobacterium-containing yogurt on triple therapy for Helicobacter pylori eradication. Aliment Pharmacol Ther 16:1669–1675

    Article  Google Scholar 

  64. Vanderhoof JA, Whitney DB, Antonson DL, Hanner TL, Lupo JV, Young RJ (1999) Lactobacillus GG in the prevention of antibiotic-associated diarrhea in children. J Pediatrics 135(5):564–568

    Article  CAS  Google Scholar 

  65. Reid G, Charbonneau D, Erb J et al (2003) Oral use of Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial in 64 healthy women. FEMS Immunol Med Microbiol 35(2):131–134

    Article  CAS  Google Scholar 

  66. Petricevic L, Unger FM, Viernstein H, Kiss H (2008) Randomized, double-blind, placebo-controlled study of oral lactobacilli to improve the vaginal flora of postmenopausal women. Europe J Obstetr Gynecol Reprod Biol 141(1):54–57

    Article  Google Scholar 

  67. Anukam K, Osazuwa E, Ahonkhai I, Ngwu M, Osemene G, Bruce AW, Reid G (2006) Augmentation of antimicrobial metronidazole therapy of bacterial vaginosis with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14: randomized, double-blind, placebo controlled trial. Microbes Infect 8:1450–1454

    Article  CAS  Google Scholar 

  68. Martinez RC, Franceschini SA, Patta MC et al (2009) Improved cure of bacterial vaginosis with single dose of tinidazole (2 g), Lactobacillus rhamnosus GR-1, and Lactobacillus reuteri RC-14: a randomized, double-blind, placebocontrolled trial. Canadian J Microbiol 55(2):133–138

    Article  CAS  Google Scholar 

  69. Martinez RC, Franceschini SA, Patta MC et al (2009) Improved treatment of vulvovaginal candidiasis with fluconazole plus probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14. Lett Appl Microbiol 48(3):269–274

    Article  CAS  Google Scholar 

  70. Ringel Y, Palsson OS, Leyer G et al (2008) Probioticbacteria Lactobacillus acidophilus NCFM ® and Bifidobacterium lactis Bi-07 improve symptoms of bloating patients with functional bowel disorders (FBD). Gastroentero 134(4 Suppl. 1):A549

    Google Scholar 

  71. www.Howaru.com

  72. http://www.naturalproductsinsider.com/news/2011/05/danisco-probiotics-reduce- bloating.aspx

  73. Tubelius P, Stan V, Zachrisson A (2005) Increasing work-place healthiness with the probiotic Lactobacillus reuteri: a randomised, double blind placebo-controlled study. Environment Health 4:25

    Article  Google Scholar 

  74. Weizman Z, Asli G, Alsheikh A (2005) Effect of a probiotic infant formula on infections in child care centers: comparison of two probiotic agents. Pediatrics 115:5–9

    Google Scholar 

  75. Lionetti E, Miniello VL, Castellaneta SP et al (2006) Lactobacillus reuteri therapy to reduce side-effects during anti-Helicobacter pylori treatment in children: a randomised placebo controlled trial. Aliment Pharmacol Ther 24:1461–1468

    Article  CAS  Google Scholar 

  76. Savino F, Pelle E, Palumeri E, Oggero R, Miniero R (2007) Lactobacillus reuteri (American Type Culture Collection strain ATCC 55730) versus Simethicone in the treatment of infantile colic: a prospective randomized study. Pediatrics 119:124–130

    Article  Google Scholar 

  77. Burton JP, Chilcott CN, Moore CJ, Speiser G, Tagg JR (2006) A preliminary study of the effect of probiotic Streptococcus salivarius K12 on oral malodour parameters. J Appl Microbiol 100:754–764

    Article  CAS  Google Scholar 

  78. Pham-Thi N, Durand H, Kerihuel JC, Bohbot S (2009) Evaluation of the effects of a synbiotic supplement on the incidence of infectious episodes in children: Randomized, controlled, multicentre study. Oral communication at the 5th Probiotics, Prebiotics AND New Foods Meeting, Rome

  79. Doron SI, Hibberd PL, Gorbach SL (2008) Probiotics for prevention of antibiotic-associated diarrhea. J Clin Gastroenterol 42(Supplement 2):S58–S63

    Article  Google Scholar 

  80. Choi CH, Jo SY, Park HJ, Chang SK, Byeon JS, Myung SJ (2011) A randomized, double-blind, placebo-controlled multicenter trial of Saccharomyces boulardii in irritable bowel syndrome: effect on quality of life. J Clin Gastroenterol 45:679–683

    Article  Google Scholar 

  81. Berman SH, Eichelsdoerfera P, Yima D, Elmerb GW, Wenner CA (2006) Daily ingestion of a nutritional probiotic supplement enhances innate immune function in healthy adults. Nutr Res 26:454–459

    Article  CAS  Google Scholar 

  82. http://www.vitacost.com/NSI-Immunobiotix

  83. De Vecchi E, Drago L (2006) Lactobacillus sporogenes or Bacillus coagulans: misidentification or mislabelling? Int J Probiotics Prebiotics 1:3–10

    Google Scholar 

  84. http://www.purecaps.com

  85. http://www.lactospore.com/benifit.htm

  86. http://www.allvita.net/probiotics.htm

  87. http://www.getwellnatural.com/probiotic-pearls.aspx

  88. http://www.lek.si/en/media-room/press-releases/571

  89. http://www.ferrosan.com

  90. http://www.ncbi.nlm.nih.gov/pubmed/16613091

  91. http://www.expresspharmaonline.com/20080430/research01.shtml

  92. Tannok GW (2003) Probiotics: time for a Dose of Realism. Curr Issues Intest Microbiol 4:33–42

    Google Scholar 

  93. Boyle RJ, Robins-Browne RM, Tang MLK (2006) Probiotic use in clinical practice: what are the risks? Am J Clin Nutr 83:1256–1264

    CAS  Google Scholar 

  94. Sheldon T (2008) Dutch trial of probiotics in acute pancreatitis is to be investigated after deaths. BMJ 336(7639):296–297

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dairy Microbiology, Sheth M C College of Dairy Science, Anand Agricultural University, Anand, 388 110, Gujarat, India

    V. Sreeja & Jashbhai B. Prajapati

Authors
  1. V. Sreeja
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jashbhai B. Prajapati
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. Sreeja.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sreeja, V., Prajapati, J.B. Probiotic Formulations: Application and Status as Pharmaceuticals—A Review. Probiotics & Antimicro. Prot. 5, 81–91 (2013). https://doi.org/10.1007/s12602-013-9126-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12602-013-9126-2

Keywords

Search

Navigation