NIH Public Access: A Gastroenterologist's Guide To Probiotics

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Clin Gastroenterol Hepatol. Author manuscript; available in PMC 2013 September 01.
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Clin Gastroenterol Hepatol. 2012 September ; 10(9): 960–968. doi:10.1016/j.cgh.2012.03.024.
A Gastroenterologist’s Guide to Probiotics

Matthew A Ciorba
Abstract
The enteric microbiota contributes to gastrointestinal health and its disruption has been associated
with many disease states. Some patients consume probiotic products in attempts to manipulate the
intestinal microbiota for health benefit. It is important for gastroenterologists to improve their
understanding of the mechanisms of probiotics and the evidence that support their use in practice.
Clinical trials have assessed the therapeutic effects of probiotics for several disorders, including
antibiotic-or Clostridium difficile-associated diarrhea, irritable bowel syndrome, and the
inflammatory bowel diseases. Although probiotic research is a rapidly evolving field, there are
sufficient data to justify a trial of probiotics for treatment or prevention of some of these
conditions. However, the capacity of probiotics to modify disease symptoms is likely to be modest
and varies among probiotic strains—not all probiotics are right for all diseases. The current review
provides condition-specific rationale for using probiotics as therapy and literature-based
recommendations.
Keywords
Clostridium difficile; IBD; IBS; irritable bowel; clinical practice; evidence based practice; Crohn’s
disease and colitis; yogurt; pouchitis
INTRODUCTION
For over a hundred years it has been recognized that certain microorganisms may impart
health benefits to the host when administered in adequate amounts. These microorganisms,
termed probiotics, have recently become a topic of significant focus in basic and clinical
investigation. Relevant to the practice of gastroenterology, probiotics are commonly used by
patients with gastrointestinal complaints or diseases. Increasingly, probiotics are also being
recommended by the clinicians who treat these conditions.1
The goal of this review is to provide clinicians with an overview of the rationale and data
which support or refute the role of probiotics for treating commonly encountered
gastrointestinal disorders. The information provided is based on review of primary literature
from randomized controlled trials (RCTs), meta-analyses, expert consensus panel
recommendations and society-based practice recommendations. References are provided for
more in depth reading and tables or figures summarize key information.
© 2012 The American Gastroenterological Association. Published by Elsevier Inc. All rights reserved.
Correspondence: Matthew A Ciorba MD, Assistant Professor of Medicine, Division of Gastroenterology, Washington University in
Saint Louis School of Medicine, 660 South Euclid Avenue, Box 8124, Saint Louis, MO 63110, mciorba@dom.wustl.edu.
Author Involvement: MAC drafted the manuscript in entirety
Disclosures: MAC received support for laboratory research from VSL Pharmaceuticals, Inc.
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our
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THE HUMAN MICROBIOME AND PROBIOTIC MECHANISMS

To understand the role that probiotics may have in influencing health, it is important to have
an appreciation of the roles of the normal intestinal microbiome (commensal microbiota).

The human gastrointestinal tract is host to over 500 bacterial species as well as a less well-
described virome. These microbiota form a virtual bioreactor facilitating digestion, nutrient
provision and the shaping of our immune system.2 Our intestinal bacteria weigh up to 1 kg
and bacterial cells outnumber human cells by 10:1. The bacterial genome may outnumber
the human genome by 100:1. Nutritional factors including several B vitamins, vitamin K,
folate, and short chain fatty acids are produced by these bacteria. Up to 10% of
anindividual’s daily energy needs can be derived from the byproducts of bacterial
fermentation. Gastrointestinal microbiota are also critical for normal immune system
development.3 The physiologic impact mediated by our resident microbes is substantial
enough to have earned the label of “other organ” from some.4
Beyond contributing to or modifying the metabolic and nutritional functions of the

commensal microbiota, probiotic bacteria have several putative mechanisms by which they
may confer specific beneficial effects. General categories include modulation of immune or
sensory-motor function, enhancement of mucosal barrier function and anti-pathogen effects
(Figure 1).5–7 Some of these mechanisms have been worked out in animal models and/or in
vitro systems only.
Soluble products secreted or shed by probiotics also mediate important physiologic benefits;
thus viable bacteria are not necessarily required for all benefits.8, 9 The mechanisms by
which probiotics exert benefit varies by specific probiotic strain and likely depends on the
clinical indication.10, 11 Therefore, as with antibiotic prescribing, clinical use of probiotics
should focus on matching the probiotic strain and dosage to the condition for which it has
shown benefit in clinical trials. In the future, greater understanding of probiotic specific
mechanisms could allow for precise selection of a particular probiotic strain to target a
patient’s specific pathogenic defect and clinical problem.
PROBIOTIC CONCEPTS FOR PRACTICE

What makes a probiotic a probiotic?
Definitions of the terms probiotic, prebiotic and synbiotic are provided in Table 1. This
review focuses on probiotics, though some probiotics have been tested as part of a synbiotic
product. Lactobacillus and bifidobacterium species are the most commonly used probiotics.
However, one of the first probiotics, which is still in use, is the non-pathogenic Escherichia
coli Nissle 1917 (ECN). Most probiotics were initially cultured from humans and resemble
known commensal gut bacteria. However, the commensal population they resemble
typically represents only a fraction of the total luminal bacteria. Saccharomyces boulardii is
a probiotic yeast strain with the potential advantage of having resistance to most antibiotics.
According to current definitions, probiotics should survive both gastric acid and bile to
reach the small intestine and colon where they exert their effects. Clinical and basic
investigations on probiotics have used a multitude of probiotic species, both as single strains
and multi-species products. Many of these probiotics are available in a lyophilized (freeze-
dried) pill form, though some are available in yogurt or as packets (sachets) which can be
mixed into non-carbonated drinks. Whether synergism or antagonism exists between
probiotic species when offered together has not been examined in clinical studies, though
both scenarios are theoretically possible. Though not exhaustive, Table 2 lists several of the
more commonly available probiotic preparations which have shown benefit in human trials.
Probiotics are considered dietary supplements; thus, they are not covered by medical
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insurance and their production is not regulated by the Food and Drug Administration. As
such, product quality, purity and viability have been reported to be variable.12 However,
several clinically tested probiotic products with quality-controlled production are now
marketed by reputable companies.
Does any yogurt work just like a probiotic?

Lactic acid producing bacteria have been used for centuries in food fermentation. Many
yogurts contain live-active lactobacillus cultures and are considered functional food
products; however, most are not considered probiotics per se. This term is reserved for
products with an adequate number of microorganisms at time of consumption specifically
shown to confer health benefits in controlled human trials. Yogurts fortified with an
adequate number of viable bacteria shown to exert benefit in controlled trials are classified
as probiotics. Given this information, and the knowledge that probiotic benefits appear
species specific, expected clinical endpoints may not be achieved by generically
recommending yogurt to patients in whom a purported probiotic benefit is desired. It should
be noted, however, that yogurt consumption has other benefits including improved lactose
tolerance and the provision of protein, vitamin D and calcium.
How long does one have to take a probiotic?

As viable microorganisms, probiotics can survive in the human gut and impact microbes
which colonize the gut. Probiotics are often detectable in the stool by culture or gene-based
assays during periods of consumption. However, many probiotic strains do not colonize the
gut and are no longer recoverable in stool 1–4 weeks after stopping consumption.13 For
example, McNulty and colleagues recently evaluated a fermented milk product with
probiotic strains matching the commercially available Activia (Dannon, White Plains, NY).
The investigators showed that the probiotic product did not change the gut’s overall bacterial
composition, but instead altered gene expression patterns relevant to carbohydrate
metabolism in the host’s resident gut microbes.14 These changes in the human fecal
“metatranscriptome” were transient, confined only to the time of the probiotic consumption.
Thus, if sustained benefit from a probiotic is desired, continued consumption is likely
required.
Where can probiotics fit into a therapeutic algorithm?

Data for probiotic use in several GI disorders is reviewed in the following section. For
antibiotic associated diarrhea and viral gastroenteritis supporting data are strong and
probiotics are among the only treatment modalities available. However, the duration of
symptoms in these conditions is typically short regardless of probiotic use. In ulcerative
colitis, pouchitis and irritable bowel syndrome adequate data exists for clinicians to consider
recommending a therapeutic trial of specific probiotic strains or preparations in selected

patients. In these conditions probiotics are usually administered as adjunctive therapy, rather
than primary or first-line therapy. The decision to recommend probiotic therapy ultimately
depends on the clinical scenario, patient interest and clinician preference. In hepatic
encephalopathy, Crohn’s disease and Clostridium difficile-associated diarrhea (CDAD),
conventional medical therapies remain the gold standard. Practice relevant probiotic
concepts are summarized in Table 3.
PROBIOTIC THERAPY FOR GASTROINTESTINAL CONDITIONS

Acute Onset Infectious Diarrhea
Several randomized controlled trials (RCTs) have evaluated the use of probiotics in acute
infectious diarrhea. The data are largely from pediatric studies where both prevention and
treatment were examined. Trials were conducted across the world with durations of up to 1
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year. In the pediatric population, rotavirus has been the most common cause of infectious
diarrhea. Data suggests that the benefit of probiotics in preventing acute infectious diarrhea
is modest.18, 21 Lactobacillus rhamnosus GG (LGG), L. reuteri and L. casei all have shown
benefit, with an approximate NNT of 7 children to prevent 1 case of rotavirus in the child
care center setting.22–24 With the currently available rotavirus vaccine in consideration, the
American Academy of Pediatrics states that probiotics for preventing acute infectious
diarrhea are not universally endorsed, but acknowledges that they may have a role in special
circumstances.18 According to the US Center for Disease Control, data is not sufficient to
support the use of probiotics such as LGG to prevent traveler’s diarrhea of bacterial origin.
The data supporting treatment of acute infectious diarrhea with probiotics are stronger. LGG
is the most effective probiotic reported on to date, reducing both severity and duration of
diarrhea by ~1 day.25, 26 The American Academy of Pediatrics supports the recommendation
of LGG early in the course of acute infectious diarrhea to reduce symptom duration.18
Antibiotic Associated Diarrhea

Antibiotic use is common in children, and diarrhea develops in ~20% of those taking
antibiotics. Prevention of non-C.difficile-related antibiotic associated diarrhea (AAD) with
probiotics has been assessed in RCTs. A 2011 Cochrane Review evaluating >3400 patients
from 16 studies concluded that the overall evidence suggests a protective effect of probiotics
in preventing AAD.27 Studies using LGG and S. boulardii produced the most convincing
results.28 The NNT to prevent one case of AAD was ~7 in the Cochrane Review. The
American Academy of Pediatrics supports the recommendation of probiotics for prevention
of, but not treatment of, AAD.18
In the adult population probiotics also appear effective in limiting AAD. A meta-analysis
evaluating studies on various probiotics and antibiotic regimens published between 1977–
2005 found that both LGG and S. Boulardii offered a reduction in risk of AAD development
(combined RR 0.31 and 0.37 respectively).29 Two recent placebo-controlled RCTs
evaluated combination probiotic products for the prevention of antibiotic associated diarrhea
as their primary endpoint. Hickson et al used the probiotic mixture currently marketed as
DanActive (Dannon, White Plains, NY) in the United States and found that it significantly
reduced AAD (12% vs. 34%) in an older cohort of hospitalized patients.30 A second study
evaluated a combination probiotic containing both L. casei and L. acidophilus (Bio-K+, Bio-
K Plus International, Quebec, Canada) in 255 patients. Patients given the higher dose of
probiotic concurrent with antibiotics (and for 5 days afterward) had fewer occurrences of
AAD (15.5 vs. 44.1%).31 As a secondary endpoint, both of these studies also showed a
reduction in development of C. difficile-associated diarrhea (discussed below).
Clostridium Difficile Associated Diarrhea

C.difficile-associated diarrhea (CDAD) is a common nosocomial and community-based
medical condition. While typically linked to antibiotic induced disturbance of the intestinal
microbiota, CDAD is now increasingly identified in patients without recent antibiotic
exposure.32 Antibiotic therapy with metronidazole, oral vancomycin and now fidaxomicin
makeup the current treatment paradigm.33 Recurrence of CDAD remains a clinical problem.
In 1994 a trial reported that S. boulardii (500mg bid) offered for 4 weeks after antibiotic
therapy reduced overall CDAD recurrence rates.34 However, the finding was only
significant for those with a history of recurrent CDAD. A follow up study, designed to be
confirmatory, did not find S. boulardii to significantly reduce CDAD recurrence after
standard therapy.35 Though a favorable trend was found in patients treated with high-dose
vancomycin (2 g/day) in the latter study, the clinical significance of this is less clear.
Lactobacillus probiotics have been tested as single species and as combination probiotic
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products for preventing CDAD recurrence. While some results have been promising, most
studies are underpowered, have methodological flaws, or have not been reproduced.36
Probiotic-based primary prevention still may be an approach to the current scourge of C.

difficile. The two recent probiotic trials discussed above in the AAD section suggest that this
may be feasible. The Hickson study reported that DanActive supplementation in older
hospitalized adults reduced AAD, but also CDAD (0% vs. 17% placebo).30 The study
evaluating the combination probiotic Bio-K+ also showed a reduction in CDAD in the
treated cohort (1.2% vs. 23.8% placebo).31 The high incidence rate of C.difficile positivity
in the placebo groups (17% and 23.8%) is a criticism for both of these studies. Nonetheless,
if confirmatory studies show similar results, these intriguing findings may lead to a
paradigm shift in managing older adults requiring antibiotic therapy.
While controversy exists, current society guidelines and expert opinion panels state that
existing data are not sufficient to justify recommending available probiotics for preventing
primary or recurrent CDAD.15, 36, 37
Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is characterized by symptoms of abdominal pain and altered
bowel habits which occur over at least three months. This common disorder is managed with
varying clinical styles as no dominant therapeutic strategy has emerged.38 The
pathophysiology of IBS remains unknown, but several lines of evidence link symptomatic
expression of this disorder with the intestinal microbiota. IBS patients may have subtle
differences in their luminal and mucosal-associated intestinal microbiota compared to
controls.39, 40 New onset IBS symptoms can develop in up to one-third of individuals after
recovery from a self-limited episode of infectious gastroenteritis.41, 42 Small-bowel bacterial
overgrowth has been reported in a proportion of IBS patients, and antibiotics offer relief of
IBS symptoms in some individuals.43, 44 So, while controversy exists, bacteria likely
contribute to at least some symptoms of IBS.45
Several clinical trials have investigated the potential for probiotics as therapy in IBS. These
trials are the subject of several single topic reviews.16, 46, 47 Systematic summarization of
these results is complicated by the inclusion of several probiotic strains/species, single or
combination preparations, dosing regimens and unique study designs. Several studies
included endpoints which were not clinically applicable or demonstrated improvement over
baseline, but not compared to placebo.16 Most studies were short term only; data on long-
term efficacy are still lacking.
A meta-analysis of 3 RCTs suggests that LGG moderately improves pain symptoms in

children with IBS (NNT=4).48 Traditional IBS treatment endpoints have not been
adequately met in studies of other single strain lactobacillus species in adults.16 A
Bifidobacterium infantis strain (B.infantis 35624, Align, Proctor and Gamble, Cincinnati,
OH) was evaluated in two clinical trials. One study found significant reductions in pain,
bloating, bowel movement difficulty and composite symptom score versus placebo and a
lactobacillus species.49 In a larger follow-up study, reduction in pain and global relief of IBS
symptoms were significantly greater in the B.infantis treated group compared to placebo.50
General recommendations from the American College of Gastroenterology as well as expert

consensus panels from both the United States and in Europe are similar.15, 17, 38 There is
reasonable rationale for why probiotics may work as treatment for IBS. There are at least
some positive controlled studies showing that probiotic supplementation reduces IBS
symptoms in some patients. The evidence of benefit is not sufficiently strong to support the
general recommendation of probiotics for IBS; however, the benefit appears greatest for
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bifidobacteria species and certain combinations of probiotics which include bifidobacteria

species rather than single species lactobacillus probiotics.
With probiotics, patients might experience a global improvement in symptomatology rather

than specific improvement in bowel function. Since treatment options for IBS remain
limited in both number and efficacy, a therapeutic trial of probiotics is reasonable for
patients interested in this approach.
Inflammatory Bowel Diseases

Evidence points to the intestinal microbiome being a key player in the development and
perpetuation of the inflammatory bowel diseases.51 Defects in the innate immune response
to commensal intestinal bacteria resulting in an exaggerated adaptive immune response to
these organisms are implicated in the pathogenesis of Crohn’s disease (CD).52 Several key
CD risk genes have functions related to bacterial killing, and antibiotics have therapeutic
efficacy in CD and pouchitis.53, 54 Compared to CD, a central role for gut bacteria is less
strongly implicated in the pathogenesis of ulcerative colitis.55 However, the evidence
supporting probiotics in patient management is better for UC and pouchitis than for CD.
Several limitations exist with trials which have evaluated probiotic therapy in the
inflammatory bowel diseases. These include small cohort sizes, use of different probiotic
doses and strains, varied treatment durations and differences in concurrent conventional
treatments. Regardless, patients with IBD often take or consider taking probiotics and
appreciate their clinician having knowledge of the topic.
Crohn’s Disease—Probiotic use in the management of Crohn’s disease is not supported

by currently available RCT data. Trials have found LGG and other lactobacilli not superior
toplacebo as an additive to standard care for inducing or maintaining remission in CD or for
preventing post operative relapse.56–58 There is also no solid data to support the use of ECN
or S. boulardii in CD.59
Ulcerative Colitis—Several published RCTs have shown benefit of probiotics in the

management of ulcerative colitis (UC). These studies have examined induction of remission
and maintenance of remission typically by comparing the probiotic to oral mesalamine or
adding the probiotic to standard therapy. ECN at 200 mg/day was similar in efficacy to 1500
mg of mesalamine for maintaining UC in remission.60
High dose VSL#3 (3.6 trillion cfu/day) has shown therapeutic efficacy in two RCTs
evaluating patients with mild-to-moderately active UC. When offered to UC patients having
a flare while on a 5-ASA or an immunomodulator, the probiotic cohort demonstrated
improved symptom-based disease activity indices and rectal bleeding, but not endoscopic
scores, compared to the placebo group.61 A study conducted in India included 144 adults
with relapsing UC and showed the VSL#3 group to have significantly higher remission rates
(42.9% vs. 15.9%) and endoscopic healing (32% vs. 14.7%).62 Most patients in both groups
remained on a stable dose of mesalamine therapy. A high dropout-rate in both groups (29%
VSL3, 59% placebo) was a limitation of the latter study. VSL#3 was also shown to improve
rates of induction and maintenance of remission in children with UC (n=29 total).63 Recent
Cochrane reviews conclude that there is insufficient data to demonstrate that probiotics have
efficacy in maintaining remission in UC; however, they have not recently addressed
induction of remission in UC.64 Single strain lactobacillus and bifidobacterium (infantis
35624, Align) probiotics did not show efficacy for maintaining UC remission in clinical
trials.65, 66
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In summary, the overall evidence suggests that ECN and VSL#3 have modest efficacy,
similar to and perhaps complementary to mesalamine, in inducing and maintaining
remission for mild-to-moderately active UC.
Pouchitis—Chronic or recurrent pouchitis is an important complication occurring in ~10–

20% of UC patients after ileal anal pouch formation surgery. VSL#3 was shown beneficial
in prophylaxis against pouchitis onset after surgical take-down 67 and in maintaining clinical
remission after antibiotic induction.68, 69 These trials were conducted in Europe and
included ~20 patients per group. A practice based report from the Cleveland Clinic found
only 19% (6 of 31) of patients who were started on VSL#3 after treatment with antibiotics to
still be taking the probiotic at 8 months.70 A single study from the Netherlands found that
compared to a historical cohort, patients taking LGG had a delayed onset of pouchitis at 3
years (7% vs. 29%).71
Clinical expert-generated guidelines concur that probiotics (VSL#3) can be effective for
preventing recurrence of pouchitis.15, 72, 73
Complications of Chronic Liver Disease/Hepatic Encephalopathy

Luminal microbiota play an important role in the pathogenesis of both spontaneous bacterial
peritonitis and hepatic encephalopathy. Ammonia produced by gut bacteria is believed to
play a key role in hepatic encephalopathy. Antibiotics are employed in clinical practice to
reduce severity or frequency of both these chronic liver disease complications. Lactulose, a
mainstay of therapy, is a prebiotic for lactobacilli which can limit bacterial ureases.
The role for probiotics in these disorders is an area of ongoing investigation.74 Treatment of
hepatic encephalopathy with lactobacillus acidophilus was studied as early as 1965.75 More
recently, Liu and colleagues offered a probiotic and prebiotic mixture to 97 patients with
minimal hepatic encephalopathy and observed a reduction in ammonia levels and
improvement in encephalopathy.76 Another group found that a yogurt-based probiotic
supplement significantly improved quantitative measurements of minimal hepatic
encephalopathy in nonalcoholic cirrhotics.77 The latter group is now completing a more
comprehensive trial using the probiotic LGG in a similar patient cohort.78
Society guidelines and expert consensus panels do not currently support a recommendation
of probiotic use for any chronic liver disease associated condition.
SAFETY OF PROBIOTICS
For most populations, probiotic consumption is considered safe and complications rare. A
review on the safety of probiotics by Snydman points out that although case reports of
bacteremia and endocarditis (LGG) as well as cases of fungemia (S. boulardii) exist,
epidemiologic evidence suggests that there is no overall increase in population-risk based on
usage data.79 This position is substantiated by a recent US government commissioned
review panel report.80 As a caveat however, a high profile multicenter placebo controlled
Dutch RCT examining probiotic supplementation in severe acute pancreatitis found a higher
incidence of mesenteric ischemia and death in the treatment group.81 This is the only trial to
date to infer such a relationship, but supports the concept that probiotics should be avoided
in critically ill patients. Indwelling central vein catheters and perhaps cardiac valvular
disease may be relative contraindications.82
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WHAT LIES AHEAD FOR PROBIOTICS IN DIGESTIVE DISEASES

Inspired investigators and technical advances in genomics are facilitating in-depth scientific
investigation of the human microbiome and the functional capacities of probiotics. These
advances are sure to bring paradigmatic changes to our fundamental understanding of how
microbiota influence health and how they can be manipulated to combat disease and
improve quality of life. Future indications and therapeutic directions for probiotics may
include conditions as diverse as mood disorders, obesity, autism and diabetes. Recent
clinical trials and translational studies suggest that lactobacillus probiotics may offer
epithelial cytoprotection to limit symptoms of radiation enteritis, a dose limiting side effect
for patients receiving abdominal radiotherapy for malignancy.8, 83, 84 Promise is held for
confirmative testing of helminth-based therapy and “turbo-probiotics” designed to secrete
human cytokines. Gene based bacterial profiling studies from disease affected humans have
identified what may be novel “probiotics” such as Faecalibacterium prausnitizii and
Clostridium species IV and XIVa. Finally, the identification, purification and repackaging of
probiotic-derived soluble factors possessing proven capacity to modify biologic function
may allow us to harness the power of probiotics while averting the potential risks associated
with live bacteria. Some suggest that as these advances progress to the clinic we will shift
from the term probiotic into the new world of pharmabiotics.85
CONCLUSIONS
Evidence supports a role for considering the recommendation of conventional probiotics for
some clinical conditions. Probiotic strain selection should focus on quality tested products
with clinically demonstrated benefit for the given disorder. Patients and physicians should
expect modest effects and consider using probiotics as a supplement to, rather than a
replacement for, conventional therapy. Though challenges exist, ongoing investigations
offer great promise for the future. Perhaps one day clinicians will have the opportunity to
use directed selection of a probiotic or probiotic derived product to specifically address a
patient’s unique disease causing physiologic or genetic defect.
Acknowledgments
Grant Support: MAC has funding from NIH grant DK089016
Work partially supported by NIH grant DK089016. I thank my colleagues at Washington University for their
critical assessment of this review and for the knowledge shared by participants at the 2011 FASEB conference on
Probiotics.
Abbreviations
CD Crohn’s disease
UC ulcerative colitis
IBS irritable bowel syndrome
RCT randomized controlled trial
AAD antibiotic associated diarrhea
CDAD Clostridium difficile-associated diarrhea
ECN E.coli Nissle 1917
LGG Lactobacillus rhamnosus GG
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Figure 1.
Mechanisms of action for probiotics in the gastrointestinal tract
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Table 1
Definitions
Ciorba
Probiotics Live microorganisms that confer a health benefit on the host when administered in adequate amounts
Prebiotic Dietary substances that nurture specific changes in the composition and/or activity of the gastrointestinal microbiota (favoring beneficial bacteria), thus conferring benefit(s) upon host
health
Synbiotics Products that contain both probiotics and prebiotics
Adapted from Reference 17
Page 15
Table 2
Common probiotic products specifically tested for gastrointestinal disorders
Ciorba
Brand Name (Company) Bacterial Species Clinical Condition Effectiveness15,16 Practice Guidelines17–19 Bacteria Count/Dosing Cost/Quantity
Activia (Dannon, White B. lactis DN-173 010, (plus yogurt IBS C 1b** 4 oz/cup, 1–4 QD $10–18/24 count
Plains, NY) starters L. bulgaricus, L. lactis and
Streptococcus thermophilus)
Align (Proctor & Gamble, Bifidobacterium infantis 35624 IBS B 1b** 1 billion/1 QD $29.99/28 count
Cincinnati, OH)
BioGaia (Everidis Health L. reuteri protectis SD2112 (ATCC Infectious Diarrhea Treatment A 1a* 100 million QD $29.99
Sciences, Saint Louis, MO) 55730 or DSM 17928)
IBS C 1b*
Bio-K+ (Bio-K plus L. acidophilus CL1285 and L. casei AAD Prevention NS 1b** 50 billion/capsule $29.99/15 count
International inc., Laval, LBC80R
QC, Canada) CDAD Prevention 1b** BID
Culturelle (Valio, Helsinki, L. rhamnosus GG (LGG) (LGG AAD Prevention A AAP, 1b*,1b** 10 billion/1 QD $18–25/30 count
Finland/Amerifit Brands, also included in Danimals yogurt,
Inc., Cromwell, CT) Dannon) Infectious Diarrhea Treatment A AAP, 1a*, 2b**
Infectious Diarrhea Prevention B 1b*, 1b**
CDAD Prevention B/C
CDAD Prevention of B/C
Recurrence
Crohn’s Disease C
IBS B/C (children) 1a*,1b**+
Danactive (Dannon. White Lactobacillus casei DN-114001 AAD Prevention A 1b** 3.1 oz/cup $5.00/8 count
Plains, NY)
Infectious Diarrhea Prevention 1b* 10 billion/cup
CDAD Prevention 1b**
Florastor (Biocodex, Inc., Saccharomyces Boulardii AAD Prevention A AAP, 1a*, 1b** 250 mg/1 BID $19.99/20 count
Creswell, OR)
Infectious Diarrhea Treatment A 1a*,1b**
Infectious Diarrhea Prevention B
CDAD Prevention B/C
Page 16
Brand Name (Company) Bacterial Species Clinical Condition Effectiveness15,16 Practice Guidelines17–19 Bacteria Count/Dosing Cost/Quantity
CDAD Prevention of B/C 1b**

Recurrence
Ciorba
Crohns C
Mutaflor (Ardeypharm, E.coli Nissle 1917 (ECN) UC Induction B 100 mg/capsule/BID $62–$81/60
Herdecke, Germany)
UC Maintenance A 1b**, BSG “A” Canada#
VSL*3 (Sigma-Tau Combination Probiotic Product IBS B/C 122.5 billion/capsule $86/30 Sachets
Pharmaceuticals, Inc., (Streptococcus thermophilus, B.
breve, B. longum, B infantis, L. UC Induction B 1b** 450 billion/sachet $52/60 count
Towson, MD)
acidophilus, L. plantarum, L.
paracasei, L. delbreuckii/bulgaricus UC Maintenance A IBS: ½–1 sachet/day
Pouchitis: Prevention and A 1b**, BSG “B” Pouchitis: 2–4 sachets/
Maintaining Remission day
UC: 1–8 sachets/day
Effectiveness based on expert panel recommendations where: A=strong, positive, well-conducted, controlled studies in the primary literature, B=some positive, controlled studies but presence of some
negative studies or inadequate amount of work to establish the certainty; C=some positive studies but clearly inadequate amount of work to establish the certainty. Practice Guidelines include those of 1)
World Gastroenterology Organisation’s global guidelines evidence level assignment17 based on the Centre for Evidence Based Medicine system20:
*
pediatrics,
**
adults,
+
as part of a multispecies probiotic product 2)American Academy of Pediatrics recommended (AAP)18 3) British Society of Gastroenterology (BSG) guidelines Grade of Evidence19 Grade A indicates
consistent results among RCTs, Grade B indicates consistent cohort studies or smaller RCTs.
#
E. coli Nissle is currently removed from the U.S. market respecting the FDA’s decision on the classification of the product as a “biologic” instead of its former status as a “medical food.”
Page 17
Ciorba Page 18
Table 3
Practical considerations relevant to probiotics in practice
• Common side effects of probiotics are typically transient but include gas and bloating.
• Different probiotic strains possess unique properties for benefiting host physiology
• One probiotic does not fit all GI illnesses; probiotic selection should be based on the clinical indication and take into consideration
the strain and dosage used in clinical trials
• Symptomatic benefits offered by probiotics are likely to be modest; thus, probiotic therapies may best be used to supplement rather
than replace conventional therapies
• Continuous consumption throughout the period of desired effect appears required for probiotics.
• Avoid probiotics in the critically ill and those with severe immune compromise

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Clin Gastroenterol Hepatol. 2012 September ; 10(9): 960–968. doi:10.1016/j.cgh.2012.03.024.

A Gastroenterologist’s Guide to Probiotics

THE HUMAN MICROBIOME AND PROBIOTIC MECHANISMS

an appreciation of the roles of the normal intestinal microbiome (commensal microbiota).

Beyond contributing to or modifying the metabolic and nutritional functions of the

PROBIOTIC CONCEPTS FOR PRACTICE

marketed by reputable companies.

Does any yogurt work just like a probiotic?

How long does one have to take a probiotic?

Where can probiotics fit into a therapeutic algorithm?

recommending a therapeutic trial of specific probiotic strains or preparations in selected

PROBIOTIC THERAPY FOR GASTROINTESTINAL CONDITIONS

Antibiotic Associated Diarrhea

Clostridium Difficile Associated Diarrhea

Probiotic-based primary prevention still may be an approach to the current scourge of C.

Irritable Bowel Syndrome

A meta-analysis of 3 RCTs suggests that LGG moderately improves pain symptoms in

General recommendations from the American College of Gastroenterology as well as expert

bifidobacteria species and certain combinations of probiotics which include bifidobacteria

With probiotics, patients might experience a global improvement in symptomatology rather

Inflammatory Bowel Diseases

Crohn’s Disease—Probiotic use in the management of Crohn’s disease is not supported

Ulcerative Colitis—Several published RCTs have shown benefit of probiotics in the

Pouchitis—Chronic or recurrent pouchitis is an important complication occurring in ~10–

Complications of Chronic Liver Disease/Hepatic Encephalopathy

WHAT LIES AHEAD FOR PROBIOTICS IN DIGESTIVE DISEASES

opinions and recommendations. J Clin Gastroenterol. 2010; 44:631–636. [PubMed: 20216432]

10. Shanahan F. Probiotics in perspective. Gastroenterology. 2010; 139:1808–1812. [PubMed:

24. Szajewska H, Kotowska M, Mrukowicz JZ, et al. Efficacy of Lactobacillus GG in prevention of

children with a mixture of three Lactobacillus rhamnosus strains--a randomized, double-blind,

diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult patients. Am J

management of irritable bowel syndrome. Am J Gastroenterol. 2009; 104(Suppl 1):S1–35.

1590. [PubMed: 16863564]

Adapted from Reference 17

CDAD Prevention of B/C 1b**

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