Floch, Martin H. MD
Division of Digestive Diseases, Yale University School of Medicine, New Haven, CT
The author declares that there is nothing to disclose.
Reprints: Martin H. Floch, MD, Division of Digestive Diseases, Yale University School of Medicine, 40 Temple Street, Suite 1A, New Haven, CT 06510 (e-mail: email@example.com).
In the 19th century, Metchnikoff first clinically proposed probiotics to be helpful to human health. He proposed that aging was due to putrefaction in the colon and that its adverse effects may be overcome by changing the flora to that of a more saccharolytic metabolism.1 It was not until the late 20th and early 21st century that the use of probiotics became popular, so much so that it is now projected to be almost a $20 billion industry.2 Manufacturers make claims that their probiotic may improve immune status and digestive health, but because of regulatory controls they make no claims pertaining to its benefits in treatment of disease.3 However, literature analysis, systematic analysis, and meta-analysis have now permitted the health care field to recommend probiotics in many clinical and disease states.4–6
The review of the literature and recommendations have come to the conclusion that probiotics may be helpful in childhood diarrhea, certain allergic and eczema conditions, ulcerative colitis, pouchitis, and in the prevention of antibiotic-associated diarrhea but less so in the prevention of Clostridia difficile-associated diarrhea.7–12
Concomitant with this literature review, the observation that bacterial therapy or fecal microbial transplant (FMT) would be helpful in treating severe C. difficile diarrhea was made. Because C. difficile infection (CDI) has become epidemic and continues to be a major problem, other sources of therapy were sought.13 Recurrent CDI has been documented clearly in 15% to 30% of patients after an initial attack. Although standard antibiotic therapy has been helpful, the recurrence rate continues to be high, and both morbidity and mortality continue to be a problem. Consequently, the emergence of FMT was appealing to physicians and patients frustrated by the recurrence and the threatening mortality of this colitis.
FMT was first used by Eiseman in 1958,14 and Brandt and Reddy15 have documented 275 cases in which it has been used with a cure rate of 89%. Most of the cases were treated by rectal or colonic installation of the transplant through colonoscopy or a rectal tube. However, Aas et al16 treated 18 patients with nasal gastric tube installation of the fecal slurry, and Garborg et al17 treated 40 patients using an upper endoscope. Hence, FMT has been used successfully following either the gastric or the colonic route.
A further advance in this therapy has now been documented by Hamilton et al18 who performed FMT through a colonoscopy but used a standardized frozen preparation instead of freshly prepared fecal slurry. Their clinical experience with 43 patients revealed that frozen prepared specimens from volunteer donors produced a 95% success rate. Four patients required a second infusion, but a 1-year analysis of these patients revealed that 41 were cured. Their patient population was somewhat unique in that 30% had inflammatory bowel disease. The majority of patients with inflammatory bowel disease improved after successful CDI treatment. This work was carried out at the University of Minnesota, where they are continuing to develop their technique. They report that they will make recommendations on therapy in the near future.18
FMT permits the administration of over 500 strains of human organisms. They certainly fit the definition of a probiotic in that they are human organisms administered to benefit health. A question that can be raised now is whether therapy with a single organism can be as effective as therapy with multiple probiotic organisms. Certainly, we now have proof that CDI is better treated with 500 species. There are many papers in the literature that demonstrate a probiotic with 8 organisms—namely, VLS#3—which is effective in ulcerative colitis,19 pouchitis,20 and Irritable Bowel Syndrome.21 The question that does arise is whether multiple organism administration is better? This will have to be answered in the future. The use of frozen fecal material removes most of the social antitheses and will enable its use in other conditions. The use of 500 species is a form of “shotgun” therapy, but it enables total biological stimulation of the immune system and seeding of the host basic flora for fermentation use, and possibly contains selective therapeutic inhibition substances such as defensins.
Borody and Khoruts22 working in Australia have reported their success in CDI, but they were also the first to begin to report success in the treatment of ulcerative colitis. It is obvious that this therapy will be tried in other conditions.23 It is an exciting time for those studying the fecal intestinal microbiome. What appeared to be an unappealing therapy with socially esthetic negatives is now moving to where frozen specimens are much more acceptable, can be developed from volunteers and not necessarily from next of kin, and have proved to be extremely beneficial in curing a very lethal complication of antibiotic therapy.18 The future holds great promise for the use of FMT and the cure of other diseases. The muddy world of the intestinal microbiome is now becoming a popular research area. We will need to answer the question “is more better?,” but we have begun to appreciate the power of poop!24
1. Metchnikoff E The Prolongation of Life. Optimistic Studies. 1907 London Butterworth-Heinemann
2. Natural Products Insider. May 23, 2008
3. Kneifel W, Salminen S Probiotics and Health Claims. 2011 West Sussex Blackwell Publishing Ltd
4. Michail S, Sherman PM Probiotics in Pediatric Medicine. 2009 Totawa, NJ Humana Press
5. Hemple S, Newberry SJ, Maher AR, et al. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systemic review and meta-analysis. JAMA. 2012;307:1959–1969
6. Floch MH, Walker WA, Madsen K, et al. Recommendations for probiotic use-2011 update. J Clin Gastroetnerol. 2001;45:S168–S171
7. Guandalini S. Probiotics for prevention and treatment of diarrhea. J Clin Gastroenterol. 2011;45:S149–S153
8. Isolauri E, Joensuu J, Suomalainen H, et al. Improved immunogenicity of oral DxRRV reassortant rotavirus vaccine by Lactobacillus casei GG. Vaccine. 1995;13:310–312
9. Bibiloni R, Fedorak RN, Tannock GW, et al. VSL#3 probiotic-mixture induces remission in patients with active ulcerative colitis. Am J Gastroenterol. 2005;100:1539–1546
10. Gionchetti P, Rizzello F, Morrelli C, et al. High-dose probiotics for the treatment of active pouchitis. Dis Colon Rectum. 2007;50:2075–2084
11. Surawicz CM. Role of probiotics in antibiotic associated diarrhea. Clostridium difficile associated diarrhea and recurrent Clostridium difficile diarrhea. J Clin Gastroenterol. 2008;42:S64–S70
12. Katz JA. Probiotics for the prevention of antibiotic-associated diarrhea and Clostridium difficile diarrhea. J Clin Gastroenterol. 2006;40:249–255
13. Kelly CP, LaMont JT. Clostridium difficile—more difficult than ever. N Engl J Med. 2008;359:1932–1940
14. Eiseman B, Silen W, Bascom GS, et al. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery. 1958;44:854–859
15. Brandt LJ, Reddy SS. Fecal microbiota transplantation for recurrent Clostridium difficile infection. J Clin Gastroenterol. 2011;45:S159–S167
16. Aas J, Gessert CE, Bakken JS. Recurrent Clostridium difficile colitis: case series involving 18 patients treated with donor stool administered via a nasogastric tube. Clin Infect Dis. 2003;36:580–585
17. Garborg K, Waagsbo B, Stallemo A, et al. Results of fecal donor instillation therapy for recurrent Clostridium difficile-associated diarrhea. Scand J Infect Dis. 2010;42:857–861
18. Hamilton MJ, Weingarden AR, Sadowsky MJ, et al. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107:761–767
19. Miele E, Pascarella F, Giannetti E, et al. Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis. Am J Gastroenterol. 2009;104:437–443
20. Gionchetti P, Rizzello F, Helwig U, et al. Prophylactis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology. 2003;124:1202–1209
21. Guandalinni S, Magazzu G, Chiaro A, et al. VSL#3 improves symptoms in children with irritable bowel syndrome: a multicenter, randomized, placebo-controlled, double-blind, crossover study. J Pediatr Gastroenterol Nutr. 2010;51:24–30
22. Borody TJ, Khoruts A. Fecal microbiota transplantation and emerging applications. Nat Rev Gastroenterol Hepatol. 2011;9:88–96
23. Backhed F, Ding H, Wang T, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA. 2004;101:15718–15723
24. Freakomonics Radio Podcast. The power of poop. March 7, 2011
© 2012 Lippincott Williams & Wilkins, Inc.