Volume 90, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Clinical research on probiotics presents challenging issues for researchers, regulators, and funding agencies, and these issues become more complex when United States federally funded research is conducted outside the United States. Here, we describe the design and results of a Phase I safety study of DSM 17938 conducted as a community-based trial under the Food and Drug Administration Investigative New Drug (FDA IND) program in a small town in the Peruvian Amazon. Forty-five healthy adults 18 to 65 years of age were randomized in a 2:1 ratio to receive either 10 organisms once daily for 5 days or an identical appearing placebo. Results showed no evidence of invasive infection resulting from probiotic administration and no differences between groups. Although we encountered several challenges in conducting an FDA-approved safety trial in this setting, the rigorously collected contextually relevant data will be very valuable to support later Phase II/III studies of for use in similar settings.


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  1. Kovatcheva-Datchary P, Arora T, , 2013. Nutrition, the gut microbiome and the metabolic syndrome. Best Pract Res Clin Gastroenterol 27: 5972.[Crossref] [Google Scholar]
  2. Behnsen J, Deriu E, Sassone-Corsi M, Raffatellu M, , 2013. Probiotics: properties, examples, and specific applications. Cold Spring Harb Perspect Med 3: a010074.[Crossref] [Google Scholar]
  3. Grover S, Rashmi HM, Srivastava AK, Batish VK, , 2012. Probiotics for human health–new innovations and emerging trends. Gut Pathog 4: 15.[Crossref] [Google Scholar]
  4. Sanders ME, Guarner F, Guerrant R, Holt PR, Quigley EM, Sartor RB, Sherman PM, Mayer EA, , 2013. An update on the use and investigation of probiotics in health and disease. Gut 62: 787796.[Crossref] [Google Scholar]
  5. Balter M, , 2012. Taking stock of the human microbiome and disease. Science 336: 12461247.[Crossref] [Google Scholar]
  6. Ceapa C, Wopereis H, Rezaïki L, Kleerebezem M, Knol J, Oozeer R, , 2013. Influence of fermented milk products, prebiotics and probiotics on microbiota composition and health. Best Pract Res Clin Gastroenterol 27: 139155.[Crossref] [Google Scholar]
  7. Hemarajata P, Versalovic J, , 2013. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therap Adv Gastroenterol 6: 3951.[Crossref] [Google Scholar]
  8. Sanders ME, , 2011. Impact of probiotics on colonizing microbiota of the gut. J Clin Gastroenterol 45 (Suppl): S115S119.[Crossref] [Google Scholar]
  9. Gueimonde M, Collado MC, , 2012. Metagenomics and probiotics. Clin Microbiol Infect 18 (Suppl 4): 3234.[Crossref] [Google Scholar]
  10. Arnold C, , 2013. The pros and cons of probiotics. Lancet Infect Dis 13: 571572.[Crossref] [Google Scholar]
  11. Slashinski MJ, McCurdy SA, Achenbaum LS, Whitney SN, McGuire AL, , 2012. “Snake-oil,” “quack medicine,” and “industrially cultured organisms”: biovalue and the commercialization of human microbiome research. BMC Med Ethics 13: 28.[Crossref] [Google Scholar]
  12. Hoffmann DE, , 2013. Health claim regulation of probiotics in the USA and the EU: is there a middle way? Benef Microbes 4: 109115.[Crossref] [Google Scholar]
  13. Hamilton-Miller JM, Shah S, Winkler JT, , 1999. Public health issues arising from microbiological and labeling quality of foods and supplements containing probiotic microorganisms. Public Health Nutr 2: 223229.[Crossref] [Google Scholar]
  14. Transparency Market Research, 2013. Probiotics Market (Dietary Supplements, Animal Feed, Foods & Beverages) - Global Industry Size, Share, Trends, Analysis, Growth and Forecast 2012–2018. Available at: http://www.transparencymarketresearch.com/probiotics-market.html. Accessed September 29, 2013. [Google Scholar]
  15. Enos MK, Burton JP, Dols J, Buhulata S, Changalucha J, Reid G, , 2013. Probiotics and nutrients for the first 1000 days of life in the developing world. Benef Microbes 4: 316.[Crossref] [Google Scholar]
  16. Preidis GA, Hill C, Guerrant RL, Ramakrishna BS, Tannock GW, Versalovic J, , 2011. Probiotics, enteric and diarrheal diseases, and global health. Gastroenterology 140: 814.[Crossref] [Google Scholar]
  17. Guandalini S, , 2011. Probiotics for prevention and treatment of diarrhea. J Clin Gastroenterol 45 (Suppl): S149S153.[Crossref] [Google Scholar]
  18. Allen SJ, Martinez EG, Gregorio GV, Dans LF, , 2010. Probiotics for treating acute infectious diarrhoea. Cochrane Database Syst Rev 10: CD003048. [Google Scholar]
  19. Iebba V, Nicoletti M, Schippa S, , 2012. Gut microbiota and the immune system: an intimate partnership in health and disease. Int J Immunopathol Pharmacol 25: 823833.[Crossref] [Google Scholar]
  20. Leone V, Chang EB, Devkota S, , 2013. Diet, microbes, and host genetics: the perfect storm in inflammatory bowel diseases. J Gastroenterol 48: 315321.[Crossref] [Google Scholar]
  21. Veerappan GR, Betteridge J, Young PE, , 2012. Probiotics for the treatment of inflammatory bowel disease. Curr Gastroenterol Rep 14: 324333.[Crossref] [Google Scholar]
  22. Rosander A, Connolly E, Roos E, , 2008. Removal of antibiotic resistance gene-carrying plasmids from Lactobacillus reuteri ATCC 55730 and characterization of the resulting daughter strain, L. reuteri DSM 17938. Appl Environ Microbiol 74: 60326040.[Crossref] [Google Scholar]
  23. Casas IA, Dobrogosz WJ, , 2000. Validation of the probiotic concept: Lactobacillus reuteri confers protection from disease in humans and animals. Microb Ecol Health Dis 12: 247285. [Google Scholar]
  24. Lionetti E, Miniello VL, Castellaneta SP, Magistá AM, de Canio A, Maurogiovanni G, Ierardi E, Cavallo L, Francavilla R, , 2006. Lactobacillus reuteri therapy to reduce side-effects during anti-Helicobacter pylori treatment in children: a randomized placebo controlled trial. Aliment Pharmacol Ther 24: 14611468.[Crossref] [Google Scholar]
  25. Savino F, Pelle E, Palumeri E, Oggero R, Miniero R, , 2007. Lactobacillus reuteri (American Type Culture Collection Strain 55730) versus simethicone in the treatment of infantile colic: a prospective randomized study. Pediatrics 119: e124e130.[Crossref] [Google Scholar]
  26. 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: 59.[Crossref] [Google Scholar]

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  • Received : 01 Nov 2013
  • Accepted : 12 Jan 2014
  • Published online : 02 Apr 2014

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