1. PROBIOTICS: A NEW
TREATMENT FOR IBS?
Anita Frankhauser, BS, RDN
Registered Dietitian Nutritionist
Agrace HospiceCare
2. What is IBS?
Irritable bowel syndrome is a GI disorder
Diarrhea Constipation
Mixed Unspecified
What is IBS? http://www.aboutibs.org/what-is-ibs.html Updated June 15, 2016. Accessed October 1, 2016.
3. What is IBS?
Reduced quality of life
Unknown cause
What is IBS? http://www.aboutibs.org/what-is-ibs.html Updated June 15, 2016. Accessed October 1, 2016.
Image: <img src=http://img.medscape.com/thumbnail_library/dt_150527_irritable_bowel_stomach_pain_800x600.jpg>
4. What is IBS?
Standard Treatment
Low FODMAP diet
Treat symptoms
What is IBS? http://www.aboutibs.org/what-is-ibs.html Updated June 15, 2016. Accessed October 1, 2016.
Image: <img src=http://img.medscape.com/thumbnail_library/dt_150527_irritable_bowel_stomach_pain_800x600.jpg>
5. Why probiotics?
• Beneficial
microorganisms
• Gut dysbiosis
• Restore healthy
gut flora
Mckenzie YA, Thompson J, Gulia P, Lomer MCE. J Hum Nutr Diet. 2016;(1). doi:10.1111/jhn.12386.
Image: http://www.medline.com/product/Florajen-3-Probiotic-Caplets/Z05-PF14196
6. PICO Question
In adults with irritable bowel
syndrome, do probiotic
supplements added to an ad
libitum diet improve constipation
to a greater degree than an ad
libitum diet with a placebo
supplement?
7. PICO Question
In adults diagnosed with irritable bowel syndrome,
do probiotic supplements added to an ad libitum diet lead
to improved constipation compared to a similar group of
adults consuming the ad libitum diet alone and a placebo
supplement?
Why this topic?
8. Study 1 Mezzasalma et al.
Purpose: multispecies
probiotics on IBS-C
symptoms
Italy
L. acidophilus, L. reuteri
VS
L. rhamnosus, B. animalis, L.
plantarum
5 billion CFU, once daily
Design: randomized
double-blind
placebo-controlled
60-day intervention
30-day follow up
no change in diet
Mezzasalma V, et al. Biomed Res Int. 2016;2016. doi:10.1155/2016/4740907.
9. Study 1 Mezzasalma et al.
Subjects: 150 adults
diagnosed with IBS-C
Italy
Outcomes: symptoms,
HR-QoL, fecal bacteria
composition
Results: Significant
reduction in constipation
amongst probiotic
groups compared to
placebo p < 0.001
Conclusions: probiotics
improve constipation,
HR-QoL
Mezzasalma V, et al. Biomed Res Int. 2016;2016. doi:10.1155/2016/4740907.
10. Study 2 Yoon JS, et al.
Purpose:
multispecies probiotic
supplements on IBS
symptoms
B. longum, B. bifidum, B.
lactis, L. acidophilus, L.
rhamnosus, S.
thermophilus
5 billion CFU, twice daily
Design: randomized,
double-blind, placebo-
controlled
2-weeks run-in
4-weeks intervention
No change in diet
Yoon JS, et al. J Gastroenterol Hepatol. 2014;29(1):52-59. doi:10.1111/jgh.12322.
11. Study 2 Yoon JS, et al.
Subjects: 49
adults with IBS
Korea
Outcomes:
symptoms, fecal
bacterial
composition
Results:
significant overall
reduction in
symptoms p < 0.05
Conclusions:
probiotics may
improve overall
IBS symptoms
Yoon JS, et al. J Gastroenterol Hepatol. 2014;29(1):52-59. doi:10.1111/jgh.12322.
12. Study 3 Sisson, G. et al.
Purpose: multispecies
probiotic on IBS
symptoms
L. rhamnosus, L.
plantarum, L.
acidophilus, E. faecium
10 billion CFU
Once daily
Design: randomized
double-blind
placebo-controlled
12-weeks intervention
Week 16 follow up
normal diet
Sisson G, Aliment Pharmacol Ther. 2014;40(1):51-62.
13. Study 3 Sisson, G. et al.
Subjects:
186 adults with IBS
London
Outcomes:
symptoms, HR-QoL,
maintenance after
intervention
Results: significant
improvement in
overall IBS symptoms
severity and bowel
habit p < 0.01
Conclusions:
probiotics may
improve overall IBS
symptom
Sisson G, Aliment Pharmacol Ther. 2014;40(1):51-62.
14. Study 4 Thijssen AY, et al.
Purpose: single-
strain probiotic on
IBS symptoms and
HR-QoL
L. casei Shirota
6.5 billion CFU
Twice daily
Design: randomized,
double-blind,
placebo-controlled,
parallel-group
4- to 6-weeks run-in
8-weeks intervention
8-weeks follow up
Normal diet
Thijssen AY, et al. Eur J Gastroenterol Hepatol. 2016;28(1):8-14. doi:10.1097/MEG.0000000000000484.
15. Study 4 Thijssen AY, et al.
Subjects:
80 adults with IBS
Belgium
Outcomes:
symptoms, HR-QoL,
cognitive score
Results:
no improvement at week
8
Improvement by week 16
P > 0.05
Conclusions:
single-strain probiotics
may not improve
constipation
Thijssen AY, et al. Eur J Gastroenterol Hepatol. 2016;28(1):8-14. doi:10.1097/MEG.0000000000000484.
16. Study 5 Begtrup, et al.
Purpose:
multispecies probiotic
on IBS management
L paracasei, L.
acidophilus,
Bifidobacterium
1.3 trillion CFU
Twice daily
Design:
randomized, double-
blind, placebo-
controlled
6-months intervention
6-months follow up
Normal diet
Begtrup LM, de Muckadell OBS, Kjeldsen J, Christensen RD, Jarbøl DE. Long-term treatment with probiotics in primary care
patients with irritable bowel syndrome – a randomised, double-blind, placebo controlled trial. Scand J Gastroenterol.
2013;48(10):1127-1135. doi:10.3109/00365521.2013.825314.
17. Study 5 Begtrup, et al.
Subjects:
131 adults
Denmark
Outcomes:
Symptoms, HR-QoL
Results:
No improvement at 6
months
No improvement in HR-QoL
P > 0.05
Conclusions:
Probiotics do not help IBS
management
Begtrup LM, de Muckadell OBS, Kjeldsen J, Christensen RD, Jarbøl DE. Scand J Gastroenterol. 2013;48(10):1127-1135.
doi:10.3109/00365521.2013.825314.
18. PICO Question
It is unclear whether
probiotics improve
constipation in adults with
IBS when added to an ad
libitum diet.
19. Conclusions
1. Probiotics still seem like a promising therapy
given the gut dysbiosis hypothesis
2. The species of microorganism may matter
3. Concentration of bacteria (CFU) may matter
4. Multispecies formulas may be more
beneficial
5. Further study isolating the IBS subtypes
would elicit clearer results
6. Further study to include diet recall data
21. References
1. What is IBS? http://www.aboutibs.org/what-is-ibs.html Updated June 15, 2016. Accessed
October 1, 2016.
2. Mckenzie YA, Thompson J, Gulia P, Lomer MCE. British Dietetic Association systematic
review of systematic reviews and evidence-based practice guidelines for the use of
probiotics in the management of irritable bowel syndrome in adults (2016 update). J Hum
Nutr Diet. 2016;(1). doi:10.1111/jhn.12386.
3. Mezzasalma V, Manfrini E, Ferri E, et al. A Randomized, Double-Blind, Placebo-
Controlled Trial: The Efficacy of Multispecies Probiotic Supplementation in Alleviating
Symptoms of Irritable Bowel Syndrome Associated with Constipation. Biomed Res Int.
2016;2016. doi:10.1155/2016/4740907.
4. Sisson G, Ayis S, Sherwood RA, Bjarnason I. Randomised clinical trial: A liquid multi-
strain probiotic vs. Placebo in the irritable bowel syndrome - A 12 week double-blind
study. Aliment Pharmacol Ther. 2014;40(1):51-62. doi:10.1111/apt.12787.
5. Thijssen AY, Clemens CHM, Vankerckhoven V, Goossens H, Jonkers DMAE, Masclee
AAM. Efficacy of Lactobacillus casei Shirota for patients with irritable bowel syndrome.
Eur J Gastroenterol Hepatol. 2016;28(1):8-14. doi:10.1097/MEG.0000000000000484.
6. Begtrup LM, de Muckadell OBS, Kjeldsen J, Christensen RD, Jarbøl DE. Long-term
treatment with probiotics in primary care patients with irritable bowel syndrome – a
randomised, double-blind, placebo controlled trial. Scand J Gastroenterol.
2013;48(10):1127-1135. doi:10.3109/00365521.2013.825314.
Editor's Notes
Hi name is Anita Frankhauser and I’m going to review 5 articles on probiotics and their potential to treat irritable bowel syndrome
I’m a registered dietitian in long-term and end of life care in Madison, WI
Irritable bowel syndrome is a common gastrointestinal disorder, affects more women than men, classified into 4 types.
People with IBS exhibit abdominal pain, discomfort and altered transit times and stool appearance more than 3 days per month
People who have IBS also report reduced quality of life. E.g. People with diarrhea-type may experience fecal incontinence. Moreover the roller coaster of GI symptoms is a large stressor for some.
The cause of IBS is unknown. However, current research implicates gut dysbiosis or altered composition of gut bacteria, increased chronic inflammation, reduced immune function and disturbances in the gut-brain axis or the neurological signaling between the gut and the brain.
Standard treatment includes symptom management and a strict elimination diet called the Low FODMAP diet to rule out offending foods. Yet, symptom management is only temporary and elimination diets are tedious, so patients and clinicians are turning to alternative therapies for relief.
Probiotics are helpful bacteria taken as supplements or food, to foster a healthy intestinal microbiome.1,2
They are naturally found in common fermented foods e.g. kimchi or yogurt.
It is thought that taking probiotics will fix gut dysbiosis and thereby improve GI function.
The current consensus is that probiotics can be tried safely, with common dosages between 10-20 billion colony forming units (CFU) for adults, However there are no guidelines on the exact strain or dosage needed.
So this brings me to my research question
This topic warrants further study, as registered dietitians are uniquely qualified to help people navigate the complexities of IBS and discern the validity of health claims on commercial products. In practice, I’ve also noticed an inconsistency in prescription of probiotics amongst patients i.e. there was no pattern to patients who had probiotics prescribed, so it made me wonder what the latest evidence was on probiotic use.
I will now review some research on probiotics and iBS.
The purpose of the article by Mezzasalma and associates published in 2016, was to determine the efficacy of a multispecies probiotic on IBS constipation type. It was a randomized, double blind placebo controlled trial testing two formulations of lactobacillus or bifidobacterium, once daily 60 days. Participants were instructed to follow their normal diet and were reassessed 30 days after the intervention.
Mezzasalma V, Manfrini E, Ferri E, et al. A Randomized, Double-Blind, Placebo-Controlled Trial: The Efficacy of Multispecies Probiotic Supplementation in Alleviating Symptoms of Irritable Bowel Syndrome Associated with Constipation. Biomed Res Int. 2016;2016:4740907.
The subjects were 150 adults diagnosed with IBS constipation type
The investigators measured changes in the following symptoms (constipation, bloating, pain, cramps, flatulence) and HR-QoL. They also measured whether the effects were maintained 30 days after intervention.
All symptoms and HR-QoL, were reported to have significantly improved in both probiotic groups compared to the placebo both after 60 days and during the follow up period. Of importance to my research question, this study indicated that probiotics could improve constipation.
Mezzasalma V, Manfrini E, Ferri E, et al. A Randomized, Double-Blind, Placebo-Controlled Trial: The Efficacy of Multispecies Probiotic Supplementation in Alleviating Symptoms of Irritable Bowel Syndrome Associated with Constipation. Biomed Res Int. 2016;2016:4740907.
Another study by Yoon and associates published in 2014, was to determine the effect of multispecies probiotics on overall IBS symptoms.
It was a randomized double blind placebo controlled trial. The probiotic contained both bifidobacterium and lactobacillus and was administered twice daily for 4 weeks. Again participants maintained their normal diet
The subjects were 49 adults diagnosed with all varieties of IBS
Five IBS symptoms were measured: abdominal pain, discomfort, bloating, stool frequency and stool form
Primary endpoint was the number of people with improved overall symptoms
Secondary endpoints: were the change in individual symptoms, stools/week, stool consistency
After four weeks of supplementation, there was a significant improvement in overall IBS symptoms in the probiotic group versus the placebo group.
Only abdominal pain, discomfort and bloating were significantly improved with probiotics. Stool frequency and stool form were not statistically different.
This is likely because the investigators grouped the iBS-C and IBS-D participants together.
So in relation to my research question, this study did not clearly determine whether probiotics improve constipation.
Sisson and associates in 2014, also studied the effect of a multispecies probiotics on IBS symptoms. The probiotic contained only bacteria of the lactobacillus genus, and was taken once daily. It was a randomized double blind placebo controlled trial in which participants were studied for 12 weeks, then reassessed on week 16. There were no changes in diet.
The subjects included 186 adults with all IBS sub-types
The investigators measured the difference in overall and individual changes in symptom severity (pain, bloating, bowel habit satisfaction, QoL)
The investigators reported a significant improvement in overall symptoms severity and bowel habits amongst the probiotics group.
In relation to my research question however, constipation was not specifically measured, (just changes in bowel habits) therefore, this study did not clearly indicate whether probiotics can improve constipation.
In a study by Thijssen and associates published in 2016, the purpose was to test the use of a single strain of lactobacillus, on IBS sx and quality of life.
The study design was a randomized double blind placebo controlled trial in which participants were followed for 8 weeks while taking probiotic twice daily, then reassessed after 8 weeks. Participants were told to maintain their normal diet.
The subjects were 80 adults diagnosed with all IBS subtypes and the outcomes were
Changes in the mean symptom score of (discomfort, pain, constipation, diarrhea, bloating) and individual changes in discomfort, pain, bloating and flatulence.
They also measured a cognitive score or perception of symptoms and QoL.
The researchers observed no improvement in MSS, QoL or cognitive score by week 8 (end of intervention), but noted improved discomfort, flatulence by week 16 (end of follow-up)
This might be attributable to the fact that the probiotic administered contained milk and sugar, two offending foods for people with IBS.
With regard to my research question, again, constipation was not measured specifically and was included in the calculation of the MSS therefore, it was unclear whether this probiotic could improve constipation.
The purpose of the last study, by Begtrup and associates published in 2013, was to determine the efficacy of a multispecies probiotic on IBS management in a primary care population.
The study design was a randomized double-blind, placebo-controlled trial in which participants were followed for 6 months during an intervention period and then reassessed 6 months after. They were also instructed to follow their normal diet.
131 adults were studied, notably that 74% were females and the outcomes were
Number of participants reporting adequate relief of symptoms and changes in symptom severity and quality of life. Symptoms measured were pain, constipation, diarrhea, early satiety and bloating.
There were significant improvements in diarrhea, early satiety and bloating by 3 months, but the effect lost by 6 months. There were no significant improvements adequate relief or quality of life
Unlike the last 3 studies, this study did specifically measure constipation. However this study did not indicate that probiotics could improve constipation.
In conclusion, given the variety of probiotics used, the study of all IBS subtypes together and the grouping of constipation with diarrhea in composite symptom scores, it is difficult to infer the efficacy of probiotics in treating constipation. Only the first study reported a significant improvement in constipation with probiotics.
By reviewing these 5 articles and reviews on this topic, I was able to come up with the following conclusions.
Probiotics are still a promising therapy given the gut dysbiosis hypothesis. Most studies report some improvement in symptoms. Probiotics are also relatively safe as most studies did not report many adverse events when taking them.
The species of probiotic may matter. While the 5 studies included many similar species of probiotics, they all varied greatly in their composition.
The concentration may also matter. All of the studies administered between 10 billion and 1.3 trillion CFU daily.
Although this is only a small sampling of the research available, The 4 studies that contained a multispecies probiotic reported some improvement in symptoms, whereas the study with only one strain reported no improvement in symptoms.
I think further study isolating the different IBS subtypes would elicit clearer conclusions
And lastly, coming from a nutrition perspective, I would also like to see diet recall data included in the design. As diet has been shown to also alter the gut microbiome.
Thank you for your time and I will now take any questions.
