Recommendations for Probiotic Use—2011 Update
Martin H. Floch, MD,* W. Allan Walker, MD,w Karen Madsen, PhD,z Mary Ellen Sanders, PhD,y
George T. Macfarlane, PhD,8 Harry J. Flint, PhD,z Levinus A. Dieleman, MD, PhD,z
Yehuda Ringel, MD,# Stefano Guandalini, MD,** Ciaran P. Kelly, MD,ww
and Lawrence J. Brandt, MDzz
Abstract: This study describes the consensus opinion of the
participants of the third Yale Workshop on probiotic use. There
were 10 experts participating. The recommendations update those of
the first 2 meetings that were published in 2005 and 2008. The
workshop presentations and papers in this supplement relate to the
involvement of normal microbiota involved in intestinal micro-
ecology, how the microbes interact with the intestine to affect our
immunologic responses, the stability and natural history of probiotic
organisms, and the role of the intestinal microbatome with regard to
affecting cardiac risk factors and obesity. Recommendations for the
use of probiotics in necrotizing enterocolitis, childhood diarrhea,
inflammatory bowel disease, irritable bowel syndrome, and
Clostridium difficile diarrhea are reviewed. As in previous publica-
tions, the recommendations are given as A, B, or C ratings. The
recent positive experiences with bacteriotherapy (fecal microbiome
transplant) are also discussed in detail and a positive recommenda-
tion is made for use in severe resistant C. difficile diarrhea.
Key Words: probiotics, recommendations, diarrhea
(J Clin Gastroenterol 2011;45:S168–S171)
wide attention of patients and health care delivery
personnel, but although there was a growing literature on
clinical trials, there were few clinical recommendations.
Hence, we gathered thought leaders and investigators in the
field and published the first workshop recommendations in
2005.1We held the second workshop with some of the
original contributors but added others to broaden our view.
The results of the second workshop were published in
This paper3represents the work of 10 experts of the
third Yale Workshop held in New Haven in April 2011.
Dr Walker and I designed this program in an effort
to include the newer concepts on the use of probio-
tics to maintain health. The work presented explores
probiotic interaction with the immune system.4
importance of these interactions to overall host health is
not yet fully understood. Questions such as how much
do supplemental probiotic organisms contribute to immune
status compared with the natural physiologic effects of
the microbiome?, can a single organism have an impor-
tant impact?, or are multiple organisms needed? are
We also included in this workshop a discussion of the
effects of colonic fermentation on health6and how it may
affect cardiac risk factors. The early concepts of how the
microbiome may affect obesity also are covered.7The
supplement includes detailed articles on all of these factors.
We reviewed the recommendations in diseases made in
2005 and 2008 and updated them. Updates on inflammatory
bowel disease,8the irritable bowel syndrome,9infectious
diarrhea,10and Clostridium difficile infection are given.11
The user should be aware that some of the recom-
mendations were made by the investigators of the first 2
workshops. All authors have cleared this publication, but
there is still controversy on some of the diseases of the
designations of an A, B, or C rating.
We have continued to use the rating system first used in
our 2005 report. This is an arbitrary system. As noted in
encyclopedic references,12there are many rating systems, and
in clinical evidence-based medicine, they are frequently
controversial. We used “A” recommendation to mean strong,
positive studies in the literature. “B” recommendation is
based on positive-controlled studies, but the presence of some
negative studies that did not support the primary outcome.
“C” recommendation is based on some positive studies, but
he first Yale Workshop on Probiotics was convened in
2004. The clinical use of probiotics had gained world-
From the *Section of Digestive Diseases, Yale University School of
Medicine, New Haven, CT; wPediatric Gastroenterology and
Nutrition Unit, Harvard Medical School, Mass. General Hospital
for Children, Charlestown, MA; zDivision of Gastroenterology,
University of Alberta, Alberta, Canada; yDairy and Food Culture
Technologies, Centennial, CO; 8Department of Bacteriology,
University of Dundee, Dundee, Tayside, UK; zRowett Institute
of Nutrition and Health, University of Aberdeen, Aberdeen,
Scotland, UK; #Division of Gastroenterology and Hepatology,
University of North Carolina School of Medicine, Chapel Hill, NC;
**Department of Pediatrics, University of Chicago Comer Chil-
dren’s Hospital, Chicago, IL; wwBeth Israel Deaconess Medical
Center, Harvard Medical School, Boston, MA; and zzDivision of
Gastroenterology, Montefiore Medical Center/AECOM, New
Dr Floch is a consultant to Dannon and Pfizer and a speaker for
Sigmatau and Procter & Gamble. Dr Walker and Dr Madsen
declares no conflict of interest. Dr Sanders has consulted with
numerous food, food ingredient, and dietary supplement companies
over the past 12 months and has received consulting fees or
honoraria for these services. She does not have any royalty,
intellectual property rights, ownership interest (eg, stocks, stock
options or other ownership interest, excluding diversified mutual
funds), or other financial benefit interests in any of these companies.
Dr Macfarlane declares no conflict of interest. Dr Flint declares no
conflict of interest. Dr Dieleman is a consultant for Abbott Canada,
Merck Canada Inc., Ferring and Abbott Nutrition. He has received
research support from Beneo-Orafti. Dr Ringel received research
grants and/or served as consultant and/or participated in advisory-
board and/or speaker for: Danisco, General Mills, Inc., Procter &
Gamble, Salix Pharmaceuticals, Ironwood Pharmaceuticals, Pfizer,
GSK and Smart-Pill. Dr Guandalini declares no conflict of interest.
Dr Kelly declares no conflict of interest. Dr Brandt is a consultant
for Optimer Pharmaceuticals, Inc.
Reprints: Martin H. Floch, MD, Clinical Professor of Medicine, Yale
University School of Medicine, Section of Digestive Diseases, 40
Temple Street, Suite 1A, New Haven, CT 06510 (e-mail: martin.
Copyrightr2011 by Lippincott Williams & Wilkins
S168|www.jcge.comJ Clin Gastroenterol?Volume 45, Supp. 3, November/December 2011
clearly inadequate amount of work to establish certainty.
Where we thought experience was inadequate or there were
too few studies for a reasonable conclusion, we made no
recommendation. This system is similar to those used in
Table 1 is an update of that published in the last
recommendations.2This table includes more clinical con-
ditions and makes recommendations that would affect the
healthy population. Some recommendations not discussed
at this workshop but those made in 2008 are included in the
table. The recommendations for C. Difficile-associated
diarrhea were downgraded from B to B/C by the
information analyzed by Na and Kelly11as compared with
that discussed in 20051and 2008.2The first recommenda-
tion was made for necrotizing enterocolitis particularly
because of the published papers on the subject from
Taiwan in 2008 which were very encouraging and the
strong meta-analysis literature. However, it must be
stressed that if probiotics are used, the strains used in a
specific reference should be followed.13,47Finally, as there
is now clinical evidence that transplanting the entire
intestinal microbiota is beneficial in severe relapsing C.
difficile diarrhea, we have presented that information as
part of our recommendations.14
We would like to emphasize that these recommenda-
tions are based on the literature that is available at this
time. It must also be stressed that these recommendations
are strain specific. Strains are listed in the table for most,
but when not listed, we provide references that can be
consulted for the strain. Anyone using these recommenda-
tions must refer to the reference and the specific strain used
in referenced studies.
TABLE 1. Recommendations for Probiotic Use—Update 2011
Clinical ConditionEffectiveness Specific Strain of Organism and Strain References
Prevention of infection
Prevention of AAD
A Saccharomyces boulardii,15LGG,16Lactobacillus reuteri SD211217 15–18
S. boulardii.19LGG,20combination of Lactobacillus casei DN114 G01,
Lactobacillus bulgaricus, snf Saccharomyces thermophilus21
Prevention of recurrent
Prevention of CDAD
B/CLGG,11S. boulardii22 11,22
A VSL#323–25 23–25
Escherichia coli Nissle27, VSL#328
E. coli Nissle,30VSL#329
E. coli Nissle,31S. boulardii,32LGG33
Bifidobacterium infantis B5624,34,35VSL#334–37,48
Lactobacillus plantarum 299V39
BLactobacillus acidophilus NCDO174813and Bifidobacterium bifidium
Recommendations From 2008*
A LGG, Lactobacillus acidophilus LAFT1, Lactobacillus plantarum,
Bifidobacterium lactis, Lactobacillus johnsonii
Atopic eczema associated
with cow’s milk allergy
LGG, Bifidobacterium lactis41
LGG, B. lactis41
C VSL#3,42L. acidophilus4342,43
Vaginosis and vaginitis
C L. acidophilus,44Lactobacillus rhamnosus GR-1,45L. reuteri RC144644–46
*Check 2008 references for further elaboration on strains used and their availability.
wReference48was made available after the workshop meeting on April 8, 2011 but believed to be significant enough to qualify this probiotic to be in a B
AAD indicates antibiotic-associated diarrhea; CDAD, Clostridium difficile-associated diarrhea; IBD, inflammatory bowel disease; IBS, irritable bowel
syndrome; LGG, Lactobacillus GG.
J Clin Gastroenterol?Volume 45, Supp. 3, November/December 2011 Recommendations For Probiotic Use–2011 Update
r2011 Lippincott Williams & Wilkins www.jcge.com|S169
There arenow manypublished meta-analyses
and ratings published and those are referred to in the
articles in this supplement. We hope that this review will be
helpful to clinicians seeking clinical advice on the use of
1. Floch MH, Madsen KK, Jenkins DJA, et al. Recommenda-
tions for probiotic use. J Clin Gastroenterol. 2006;40:275–278.
2. Floch MH, Walker WA, Guandalini S, et al. Recommenda-
tions for probiotic use-2008. J Clin Gastroenterol. 2008;
3. Floch MH, Walker WA, Madsen K, et al. Recommendations
for probiotic use-2011 Update. J Clin Gastroenterol. 2011;45.
4. Madsen K. Interactions between microbes and the gut
epithelium. J Clin Gastroenterol. 2011;45:S111–S114.
5. Sanders ME. Impact of probiotics on colonizing microbiota of
the gut. J Clin Gastroenterol. 2011;45:S115–S119.
6. Macfarlane G, Macfarlane S. Fermentation in the Human
Large Intestine; Its Physiologic Consequences, and the
Potential Contribution of Prebiotics. J Clin Gastroenterol.
7. Flint HJ. Obesity and the microbiome. J Clin Gastroenterol.
8. Meijer BJ, Dieleman LA. Probiotics in the treatment of human
inflammatory bowel diseases: update 2011. J Clin Gastro-
9. Ringel Y, Ringel-Kulka T. The rationale and clinical
effectiveness of probiotics in irritable bowel syndrome. J Clin
10. Guandalini S. Probiotics for prevention and treatment of
diarrhea. J Clin Gastroenterol. 2011;45:S149–S153.
11. Na X, Kelly C. Probiotics in Clostridium difficile infection.
J Clin Gastroenterol. 2011;45:S154–S158.
12. Evidence-based medicine. In Wikipedia. Retrieved June 26,
2011 from http://en.wikipedia.org/wiki/Evidence-based_medicine.
13. Ganguli K, Walker WA. Probiotics in the prevention of
necrotizing enterocolitis. J Clin Gastroenterol. 2011;45:S133–S138.
14. Brandt LJ, Reddy SS. Fecal microbiotic transplantation for
recurrent Clostridium difficile infection. J Clin Gastroenterol.
15. Szujewsku H, Skorka A, Dylag M. Meta-analysis. Sacchar-
omyces boulardii for treating acute diarrhea in children.
Aliment Pharmacol Ther. 2007;25:257–264.
16. Guandalini S, Pensabene I, Zikri MH, et al. Lactobacillus GG
administered in oral rehydration solution to children with
acute diarrhea: a multi-center European Trial. J Pediatr
Gastroenterol Nutr. 2000;30:54–60.
17. Shornikova AV, Casus I, Isolauri E, et al. Lactobacillus reuteri
as a therapeutic agent in acute diarrhea in young children. J
Pediatr Gastroenterol Nutr. 1997;24:399–404.
18. Guandalini S. Probiotics for children with diarrhea: an update.
J Clin Gastroenterol. 2008;42:S53–S57.
19. Surawicz CM. Role of probiotics in antibiotic associated
diarrhea, Clostridium difficile associated diarrhea and recurrent
Clostridium difficile diarrhea. J Clin Gastroenterol. 2008;42:
20. Doron S, Hibberd P, Gorbach SL. Probiotics for prevention of
antibiotic-associated diarrhea. J Clin Gastroenterol. 2008;42:
21. Hickson M, D’Souza AL, Muthu N, et al. Use of probiotic
Lactobacillus preparation to prevent diarrhea associated with
antibiotics: randomized double blind placebo controlled trial.
22. Katz JA. Probiotics for the prevention of antibiotic-associated
diarrhea and Clostridium difficile diarrhea. J Clin Gastroenterol.
23. Gionchetti P, Rizzello F, Venturi A, et al. Oral bacteriotherapy
as maintenance treatment in patients with chronic pouchitis: a
double-blind, placebo-controlled trial. Gastroenterology. 2000;
24. Gionchetti P, Rizzello F, Helwig U, et al. Prophylactis
ofpouchitis onset with
blind, placebo-controlled trial. Gastroenterology. 2003;124:
25. Mimura T, Rizzello F, Helwig U, et al. Once-daily high-dose
probiotic therapy (VSL#3) for maintaining remission in
recurrent or refractory pouchitis. Gut. 2004;53:108–114.
26. Gionchetti P, Rizzello F, Morselli C, et al. High-dose
probiotics for the treatment of active pouchitis. Dis Colon
27. Rembacken FJ, Snelling AM, Hawkey PM, et al. Nonpatho-
genic Escherichia coli versus mesalazine for the treatment
of ulcerative colitis: a randomized trial. Lancet. 1999;354:
28. 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.
29. Miele E, Pascarella F, Giannetti E, et al. Effect of a probiotic
preparation (VSL#3) on induction and maintenance of remis-
sion in children with ulcerative colitis. Am J Gastroenterol.
30. Kruis W, Fric P, Pokrotnieks J, et al. Maintaining remission of
ulcerative colitis with the probiotic Escherichia coli Nissle 1917
is as effective as with standard mesalazine. Gut. 2004;53:
31. Malchow HA. Crohn’s disease and Escherichia coli: a new
approach in therapy to maintain remission of colonic Crohn’s
disease. J Clin Gastroenterol. 1997;25:653–658.
32. Guslandi M, Mezzi G, Sorghi M, et al. Saccharomyces
boulardii in maintenance treatment of Crohn’s disease. Dig
Dis Sci. 2000;45:1462–1464.
33. Gupta P, Andrew H, Kirschner BS, et al. Is Lactobacillus GG
helpful in children with Crohn’s disease? Results of a
preliminary open-label study. J Pediatr Gastroenterol Nutr.
34. Whorwell PJ, Altringer L, Morel J, et al. Efficacy of an
encapsulated probiotic Bifidobacterium Infantis 35624 in
women with irritable bowel syndrome. Am J Gastroenterol.
35. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and
Bifidobacterium in irritable bowel syndrome (IB): symptom
responses and relationship to cytokine profiles. Gastroenterol-
36. Kim JH, Camilleri M, McKenzie S, et al. A randomized
controlled trial of a probiotic, VSL#3 on gut transit and
symptoms in diarrhea-predominant IBS. Aliment Pharmacol
37. Kim JH, Vazquez Roque MI, Camilleri M, et al. A randomized
controlled trial of probiotic combination VSL#3 and placebo
in IBS with bloating. Neurogastroenterol Motil. 2005;17:
38. Guyonnet D, Chassany O, Ducrotte P, et al. Effect of a
fermented milk containing Bifidobacterium animalis DN-172
010 on the health-related quality of life and symptoms in
irritable bowel syndrome in adults in primary care: a multi-
centre, randomized double-blind, controlled trial. Aliment
Pharmacol Ther. 2007;26:475–486.
39. Niedzielin K, Kordecki H, Birkenfeld B, et al. A con-
trolled, double-blind, randomized study on the efficacy
of Lactobacillus plantarum 299 V in patients with irritable
bowel syndrome. Eur J Gastroenterol Hepatol. 2001;13:
40. 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.
41. Isolauri E, Salminen S. Probiotics: use in allergic disorders. J
Clin Gastroenterol. 2008;42:S91–S96.
42. Delia P, Sansotta G, Donato V, et al. Prevention of radiation-
induced diarrhea with the use of VLS#3, a new high-
potency probiotic preparation. Am J Gastroenterol. 2002;97:
Floch et alJ Clin Gastroenterol?Volume 45, Supp. 3, November/December 2011
r2011 Lippincott Williams & Wilkins
43. Salminen E, Eloman I, Minkkinen J, et al. Preservation
of intestinalintegrity during
44. Hilton F, Isenberg HD, Alperstein P, et al. Ingestion of yogurt
containing Lactobacillus acidophilus as prophylaxis for candi-
dal vaginitis. Am Intern Med. 1992;116:353–357.
45. Anukam K, Osazuwa E, Ahonkhai I, et al. Augmentation
of antimicrobial metronidazole therapy of bacterial vaginosis
with oral probiotic Lactobacillus rhamnosus GR-1 and
Lactobacillus reuteri RC-14: randomized, double-blind, place-
bo controlled trial. Microbes Infect. 2006;8:2772–2776.
46. Anukam KC, Osazuwu E, Osemen GI, et al. Clinical study
comparing probiotic Lactobacillus GR-1 and RC-14 with
metronidazole vaginal gel to treat symptomatic bacterial
vaginosis. Microbes Infect. 2006;8:2772–2776.
47. Lin HC, Chyong-Hsin H, Hsiu-Lin C, et al. Oral probiotics
prevent necrotizing enterocolitis in very low birth rate preterm
infants: a multicenter, randomized, controlled trial. Pediatrics.
48. Guandalini S, Magazzu G, Chiaro A, et al. VSL#3 improves
symptoms in children with irritable bowel syndrome: an
international, randomized, placebo-controlled, double-blinded,
cross-over study. J Pediatr Gastroenterol Nutr. 2010;51:24–30.
J Clin Gastroenterol?Volume 45, Supp. 3, November/December 2011Recommendations For Probiotic Use–2011 Update
r2011 Lippincott Williams & Wilkins www.jcge.com|S171