Examining the Efficacy of
Probiotics in the treatment of
Irritable Bowel Syndrome:
A Literature Review
Micaela Kraft
12/2/2013
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Introduction
Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder
and is the most diagnosed disorder by gastroenterologists resulting in 2.4-3.5 million visits
annually in the US1. According to the International Foundation of Functional Gastrointestinal
Diseases (IFFGD), the condition is prevalent in 10-15% of the US population depending on how
the diagnosis is defined, and it is 1.5 times more prevalent in women than men1. The burden of
economic loss due to IBS is approximately $20 billion in expenditures annually which stems
from not only its high prevalence, but the high use of diagnostic resources and treatments1 .
There are multiple diagnostic criteria that use different methods of diagnosis. The main criteria
seen in studies include Rome I, II, and III, Manning, and Kruis3. These criteria differ mainly in
the symptoms used to diagnose a patient of IBS. Manning criteria was the first criteria used to
diagnose IBS. Then, Rome I, II, and III build upon his criteria by adding different symptoms or
taking some away. They are in consecutive order of when they were established: from oldest to
most recent. Kruis is also a criteria that has built on to Manning’s. Some complications leading
to IBS include hypersensitivity in the gut, disturbance of motility and secretion through the
digestive tract, inflammation of the intestine, and dysfunction of the autonomic nervous system2.
The main symptoms include mild to severe abdominal pain and bloating, accompanied by
diarrhea or constipation. Emotional distress and depression can also be related to IBS.. Due to
constant pain and discomfort, IBS lowers the overall quality of life of those who suffer,
warranting the identification of an effective treatment.3
Since IBS is a painful condition, treatments are being researched to determine if
probiotics can help alleviate the pain of sufferers and improve their overall quality of life. This
could help decrease the amount of job absences and frequent trips to the physician, along with
making everyday tasks easier3. The most popular treatments are making changes to the diet and
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taking medications such as laxatives and anti-diarrheal agents, but many of these methods are
found to be unsatisfactory4. Therefore, alternate treatment methods are being investigated,
specifically the use of probiotics. Probiotics are living organisms that perform many health
benefits to their host when they are ingested in sufficient amounts. It is suggested that probiotics
are specifically beneficial for patients with IBS and lead to a better quality of life. Probiotics
have the ability to alter bowel flora and replace gas-producing bacteria. They are also suggested
to improve immune activity in the mucosa 4. The benefits of probiotics could possibly provide
great relief for those who suffer, but some studies show otherwise3. Much research is being
conducted to examine possible benefits; however, the studies present varying, conflicting results:
therefore the purpose of this paper is to examine the efficacy of probiotics in the treatment and
management of IBS by reviewing and comparing recent clinical trials.
Methods
Clinical trials were found through searching the databases CINAHL, Academic Search
Complete, and MEDLINE. The main keywords used to search through these databases were;
“probiotics” and “irritable bowel syndrome” using the Boolean operators, AND and OR. It also
helped to check off the box in advanced search that says, “Clinical trials” so that the search was
narrowed down to only clinical trials. A few different combinations were used in the search
process, but the most successful one was, “Probiotics AND irritable bowel syndrome treatment
OR IBS treatment AND trial.” This combination presented 172 results that were useful to the
topic. Of these 172 results, thirteen clinical trials were analyzed and deemed valuable with
results on whether or not probiotics were beneficial in the treatment of IBS. Two articles were
discovered by using the sources in a previous review article with a similar subject. The articles
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that were excluded included ones that were not clinical trials, performed prior to 2008, and were
not published in academic journals. One article was excluded due to two publications in different
journals. The more recently published article was used. To determine the articles were reliable, I
ensured the journal they were from was peer-reviewed.
Results
Statistically Significant Improvement in One or More IBS Symptoms
There were seven articles that had trials resulting in statistically significant improvement
of one or more symptoms of IBS, including the Global Symptom Score (GSS). Every trial was
from a different peer-reviewed journal and included Agrawal et al., Guyonnet et al., Enck et al.,
Gugliemetti et al., Capello et al., Williams et al., and Zeng et al6,7,8,9,10,11,12. It was important to
examine these articles in depth to see why they may have found significance while other trials
failed to do so. Every trial used a different strain of probiotics, six of them being multi-strain and
one being singles-strain6,7,8,9,10,11,12. Two of the multi-strain probiotics included symbiotics in the
mixture8,9. Symbiotics are a mixture of probiotics and prebiotics which allows for synergetic
effects by prebiotics acting as a substrate for the probiotics8. The trials that examined symbiotic
mixtures were Capello et al., which used the commercial mixture, Probinul®, and Enck et al.,
which used the commercial mixture Prosymbioflor®8,9.
Out of the seven trials showing statistical significant improvement, three of them show
significant improvement of the Global Symptom Scores. The Global Symptom Score (GSS) is
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the average score of all IBS symptom severity11. These trials included Enck et al., Guglielmetti et
al., and Williams et al9,10,11. Guglielmetti et al. was a crossover trial using a 9-point Likert scale
where the lower the score, the less severe the symptom. Improvement was seen from the run-in
phase that resulted in a score of 2.95 to the treatment phase where the score was 2.07. These
results show IBS symptoms were significantly improved by -0.88 points (95% Confidence
Interval (CI): -1.07- 0.69)9. Since, zero is not included in the confidence interval, the
improvement is statistically significant.
Enck et al., carried out a randomized double blind placebo-controlled trial and their
resulting mean GSS was 3.27 points (95% CI: 2.41-5.05)10. Again, zero is not included in the
confidence interval, concluding a statistically significant association of probiotics and global
symptom scores10. Williams et al. found their results by expressing significance at p<0.05 while
using an analysis of variance (ANOVA) model throughout the study. The resulting p-value for
the GSS was p=0.034 at week 6 and p=0.021 at week 8, which are both significant improvement
of global symptom scores11.
Two of the trials both used Activia® as their source of probiotics and had different
results. These trials were Agrawal et al. and Guyonnet et al6,7. Both of the trials were selfassessed through symptom scores6,7. Guyonnet et al. used an open label method and had 360
participants7. Agrawal et al., on the other hand, used a double blind method and only thirty
participants6. Interestingly, both of the trials were carried out in the same year, 2009. Guyonnet
et al. resulted in significant improvement in almost all symptoms with a p-value of p<0.001
being significant7. While Agrawal et al., who used p<0.05 to express significance, saw
improvement in overall IBS severity (p=0.032) and a decrease in abdominal pain (p=0.044)6.
Although, these studies had some similarities, there are a few differences between them that may
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count for their slightly different results. The main factor is probably the difference in sample
size, Guyonnet et al. have a better representation of the population with 360 participants6. Also,
Agrawal et al. only used females in their study, which is not much of a representation of the
population6.
There were also a few trials that showed significant improvement in the severity of one or
more specific symptoms of IBS8,12. In the trial by Capello et al., significant reduction in the
frequency of flatulence was observed. They found their results by expressing significance at
p<0.05 while using an analysis of covariance (ANCOVA) model throughout the study8. The pvalue for flatulence was p=0.038, making it a significant association with probiotics8. Flatulence
is a symptom of IBS that could potentially decrease the quality of life in people who suffer,
making this finding an essential step in the overall improvement in the lives of IBS patients8 .
There are a few IBS sub-categories where there is one symptom of IBS that is predominant over
others12. Zeng et al., whose trial used multi-strain probiotics in the form of fermented milk,
focused on decreasing permeability in patients with D-IBS which is a condition that is
predominantly diarrhea12. A significant decrease in permeability was found. They expressed
significance as p<.05 and the p-value for bowel permeability, as compared with baseline, was
p=.023. This shows us there was a significant decrease in bowel permeability in comparison to
the baseline values12.
Although, all of these studies had significant findings in favor of probiotics, there were
some adverse events that occurred. The common side effects that were reported were gastric
pain, diarrhea, abdominal pain, and heartburn7, 9, 12. It is unsure if these events are due to the
probiotics or some other factors. The studies in this subsection suggest probiotics may be helpful
in improving the symptom relief satisfaction of those suffering from IBS.
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Clinical Improvement, with No Statistical Significance
Out of the thirteen clinical trials collected, there were three that resulted in clinical
improvement in overall IBS symptoms, but no statistical significance was found to support it.
These studies were carried out by Gawronska., et al., Simrén et al., and Roberts et al13,14,15. There
was one particular similarity between all three clinical trials; they all used the randomized,
double-blind, placebo controlled study design13,14,15. This study design is known for providing
the strongest evidence on the efficacy of preventive and therapeutic clinical trials14. This is
important to note when examining the design in clinical trials. These three all used this strong
design and gained similar results.
One study had results that were statistically significant, yet did not present an
improvement in the severity of IBS symptoms. This study was by Gawronska et al. was the only
study found to use children as their subjects13. Their trial resulted in a significant decrease in
frequency of abdominal pain in children after consuming a capsule filled with Lactobacillus
rhamnosus GG (LGG) twice a day for 4 weeks13. The p-value used to express significance was
p<.05. The p-value for frequency of pain was p=0.02. These results show an important
significance of children experiencing pain less often, but the p-value for the severity of pain was
p=0.10, concluding no statistical improvement in the severity of pain in children with IBS13.
There was no other statistical significance confirming a change in the severity of pain or severity
of any other symptom included in the Rome II criteria. This trial concluded in moderate probiotic
treatment success on children with IBS13.
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Along with the study design, the way the probiotics are administered also plays an
important role in the final results. As Gawronska et al. used probiotic-filled capsules13, Simrén et
al. and Roberts et al., used dairy products to administer the probiotics14,15. Roberts et al. used a
milk product fermented with probiotic strains Bifidobacterium lactis, Bifidobacterium
bulgaricus, and Streptococcus thermophilus, all three of which are commonly found in
commercial dairy products15. Statistical significant improvement was reported throughout the
trial from all participants, but the results did not differ between the probiotic and placebo
group15. Interestingly, in week 8 the placebo group had resulted in statistically significant
improvement of adequate relief. Using p<0.05 to express significance, the p-value for adequate
relief for the placebo group was p=0.0315.
Simrén et al. also used a milk product fermented with probiotic strains Lactobacillus
acidophilus, Lactobacillus paracasei, and Bifidobacterium lactis, also three common probiotics
found in commercial dairy products14. This trial had very similar results as Roberts et al. had.
Significant improvement was seen in both groups during the treatment period, but there was no
difference between the groups. Using p<0.05 to express significance, the IBS symptoms had a pvalue of p=0.23 showing no statistical difference between groups14. Since statistically significant
improvement was observed in both groups in two different trials and in one improvement was
seen in the placebo group, it could be suggested that the improvement was due to the
consumption of the milk product rather than the probiotics14,15. This suggestion would call for
further research.
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Trials Resulting in Unfavorable Effects
There was one study, Farup et al., out of the thirteen that displayed an unfavorable effect
of probiotics on the subjects in the trial16. Adults with IBS symptoms under Rome II criteria
were recruited from a gastroenterologist outpatient clinic. The study design was a randomized
double-blind, placebo-controlled cross-over trial. They used a strain of probiotics called L.
Plantarum M 1298 and it was administered by a capsule16. The subjects were randomized into
two groups and were instructed to take one capsule, either placebo or probiotic, for two weeks
and then switched their treatment and proceeded the other treatment for 2 more weeks. This was
a double blind trial16.
The results presented the mean number of weeks with satisfactory relief in the probiotic
period of the trial as 0.50 weeks and in the placebo period as 1.44 weeks out of three weeks. The
p-value used to express a significant difference between groups was p<0.0516. The resulting pvalue between groups from number of weeks with satisfactory relief was p=0.006 in favor of the
placebo period16. Results for preference was also included, also using p<0.05 to express
significance. The trial observed thirteen of the sixteen participants preferred the placebo to the
probiotic with a p-value of p=0.01216.
This is the first trial that has observed unfavorable effects on subjects caused by
probiotics on IBS patients16. The study did not present what the specific unfavorable effects
were. A possible reason for these results could be the specific strain of the probiotics used. L.
Plantarum M 1298 was not used in any other studies that were analyzed in this article. Another
altering factor of the study could have been the condition of the subjects during the active period.
Things to take into account could be their diet, if they were under stress, and other conditions
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that could affect IBS symptoms16. They also had a small sample size, which is not very
representative of the population living with IBS16.
These findings are rare in clinical trials with probiotics16. Since it is the only clinical trial
examining the efficacy of probiotics on IBS symptoms to have these results, there is no
conclusion that probiotics are unfavorable to patients with IBS.
No Improvement Observed
Two of these thirteen articles showed little to no improvement from probiotic treatment.
These trials were carried out by Amirimani et al., and Inci et al17,18. These two trials presented
results that were not significant and did not show probiotics to have much effect at all on treating
IBS symptoms.
Amirimani et al. conducted a randomized, single-blind, placebo-controlled trial carried
out on 92 patients over four weeks17. The probiotic used was Lactobacillus reuteri, or Biogaia®,
and was administered by capsule17. Using p<0.05 to express significance, the results showed no
statistical significance between groups, but a significant improvement in the frequency of
defecation was observed in both groups (p=0.048 for the placebo group and p=0.050 for the
probiotic group)17.
Inci et al., conducted a randomized, unblind, control trial using the commercial yogurt
brand, Activia®18. Unlike the study by Amirimani et al., this study only had 9 participants and
they were recruited by email. This study found no statistically significant differences between the
placebo and probiotic groups18. The main symptom examined was oro-caecal transit time
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(OCTT) which was higher in the control group than the probiotic group, but not significantly
(p=0.381 under a significance expressed by p<0.05)18.
Both groups did not come to a conclusion about the efficacy of probiotics on IBS
symptoms. There are a couple limitations to their studies which may lead to the reason for lack
of significant results. Amirimani et al., had a very short period of two weeks that was observed17.
This may not have been enough time to observe an improvement by probiotics. During these two
weeks they were asked to complete the questionnaire twice a week17. This means they only filled
out four questionnaires. This is not much information to analyze. Inci et al. also had a problem
with not gathering enough information and had only nine participants, which is very few
compared to the number of people who suffer with IBS17. Both studies had to adjust results for
cofounders such as location, diet, age, etc17,18. In conclusion these studies did not provide us with
enough information to help conclude the amount of efficacy probiotics have on IBS.
Discussion & Limitations
Overall, there were seven out of thirteen studies that presented positive statistical
significance in the improvement of IBS symptoms (54%)6,7,8,9,10,11,12. Three studies showed
clinical improvement (23%)13,14,15, two studies showed no improvement (15%)16,17 and one
observed unfavorable effects of probiotic treatment (8%)18. With a range of results from positive
improvement to unfavorable improvement, gives reason to observe deeper the limitations and
different methods and how they affected results.
The subjects used in the studies are meant to be representative of the population of people
suffering from IBS. The subjects in a study can alter the results greatly if they are not completely
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representative. Throughout these studies there were mainly adult subjects, but the number of
participants varied. Two studies used specific groups of patients. The study by Gawronska et al.,
analyzed 112 children as subjects13. It is important to study children since they also suffer from
this uncomfortable condition, but the study had the children self-assess their symptoms with help
from their parents using a face scale. It is hard to rely on children’s responses when using this
scale. There was only one follow-up meeting at the end of the study with a physician. For the
reason that children were self –assessing their symptoms, results may not be as reliable13.
Another study using a specific subject group was Agrawal et al., who used only women as their
subjects6. IBS is more prevalent in women making this appropriate to try and find results
specifically for women6. At the same time, it is not completely representative of the IBS
population.
All of the other studies used adults as subjects, but only a few studies used constructive
follow ups, such as multiple telephone calls and multiple follow up physician visits 6,8. Followups are also very important in assessing data, especially when the results are self-assessed. A
follow-up can ensure that the subjects are performing the study correctly in order to accurately
analyze results. The majority of studies that did not use follow ups, resulted in no statistical
significance.
The study design is also very crucial when it comes to results. All studies used strong
study designs, seven were randomized double-blind, placebo controlled trials, two were
crossover studies, two were parallel studies, two were open label, and one was a single-blind
randomize control trial. The way the study is carried out will have an effect on how the results
are analyzed. For example, the open label study could have a bias effect on results7. Another
example is crossover studies call for analyzing results in a different manner than randomized
13
control trials. It is important to note that the two crossover studies found examined in this review
both found statistical significance, but in the opposite directions; one being a positive
improvement and one resulting as unfavorable10,16. This goes to show the range of results that
can occur from a similar study design. All of the double-blind randomized control trials resulted
in either statistical significant improvement or clinical improvement. As these types of study
designs are seen to be very strong, this kind of results can lead us to suggest probiotics may have
a positive effect on the symptoms of IBS.
It is suggested that the strain of probiotic could also have an effect on the end results. Out
of these studies, three used a single strain of probiotics that were all administered through
capsules. One of these single strains was L. Plantarum M1298 and was the only study to use this
probiotic and found unfavorable effects, suggesting that the type of probiotic may indeed have an
effect on the end result16. The rest of the studies used multi-strains of probiotics and were mostly
administered through fermented milk or yogurt. Two of them used symbiotics, which is a
mixture of pre- and probiotics, and three of them used Activia® as their source of probiotics6,7,18.
There was a range of results from the studies using Activia®. Two of them statistically improved
IBS symptoms, while one study showed no improvement6,7. The two symbiotic mixtures both
resulted in statistically significant improvement, suggesting that symbiotics may work better in
the improvement of symptoms8,9.
An interesting occurrence in two studies, Guyonnet et al and Roberts et al, was both the
probiotic group and the placebo group had observed sustained improvement7,15. Both of these
studies used fermented milk as their way of administration. A significant improvement in both
groups makes it hard to tell if the improvement was due to the probiotics or the milk product
14
alone, since the group with the milk product alone improved as well. Results as these call for
further research.
Further Research
There are a few factors seen throughout these thirteen studies that need further research
before making a conclusion. One factor being the strain of probiotic used. From these results, it
is suggested that the outcome may be based on what strain is used, but further research could
present if different strains work in different ways. It is possible that some of the strains have
better ability to build up microbiota in the gut, while others may not.
Other than the specific strain used, there could be more research on whether a multistrain or single-strain provides more benefits. With a multi-strain more types of probiotics are
being administered, but in the case that the type of probiotic is important, you may want to build
up only one strain. It would also be helpful to further look into how probiotics react in different
administration methods. The two administration methods seen here were through either capsules
or fermented milk or yogurt products. It could be suggested that one way of ingesting probiotics
is better than the other.
Lastly, it would be important to further examine the effect of symbiotics versus probiotics
on the efficacy of improving IBS symptoms. The symbiotics provide both prebiotics and
probiotics making the gut a better environment for probiotics to grow.
15
Conclusion
From this review, it is suggested that probiotics may be effective in alleviating the
uncomfortable symptoms experienced by IBS patients. Further research must be done to examine
the different factors that may have altered some results. More studies should be done on the
efficacy of symbiotics, as well, since they are suggested to be significantly effective by two
studies in this article. IBS is a very uncomfortable disease prevalent in many patients in the US.
It reduces patients’ quality of life, productivity, and sometimes can make them emotionally
distressed. With further research and more strong clinical trials, it would be very valuable to find
a possible treatment for sufferers of IBS.
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