Gut-related symptoms, including flatulence, bloating, heartburn, nausea, vomiting, constipation, diarrhoea, food intolerance, incontinence, and abdominal pain affect approximately one third of the general population, according to the World Gastroenterology Organisation. Among the functional gastrointestinal disorders (FGIDs) that are characterized by persistent and recurring GI symptoms, irritable bowel syndrome (IBS) affects around 11% of the population globally and can interfere with everyday activities and quality of life.
Evidence suggests that the gut microbiota play an important role in gastrointestinal disorders. Probiotics in the context of personalized dietetic recommendations may affect many GI disorders through their ability to alter the dysbiotic gut microbiota or change patients’ tolerance to their own commensal gut microbiota. Several randomized controlled trials support the efficacy of probiotics as a coadjuvant treatment in different functional bowel disorders in both paediatrics and adult populations.
As gastrointestinal and digestive disorders account for one in 10 consultations in primary care, healthcare practitioners face the challenge of finding evidence-based information on how to prevent lower GI symptoms and decide which probiotic to recommend—which strain and formulation, at what dose, using what mode of administration, and for how long. Besides this, it is not possible to extrapolate the results of a particular study with one species of probiotic, one dose, and one formulation in one GI disorder to other probiotics. Therefore, there is a need for guidelines and advice for prescribing probiotics in clinical practice for GI disorders.
A recent systematic review, led by Prof. Pali Hungin from the School of Medicine and Health at Durham University and on behalf of the European Society for Primary Care Gastroenterology, provides an update on the use of probiotics in the treatment of lower GI symptoms in adults.
By compiling data from January 2012 to June 2017, the authors included a total of 70 randomised, placebo-controlled trials (RCTs) (33 newly identified studies in addition to 37 publications in the original review published in 2013). Indications examined were irritable bowel syndrome (IBS), 34 studies; diarrhoea associated with antibiotics, 13 studies; diarrhoea associated with Helicobacter pylori eradication therapy, 7 studies; other conditions, 16 studies. The new review covers the role of probiotics in patients with other GI conditions, such as healthy individuals with minor GI complaints, patients with lactose intolerance and those receiving antibiotics or undergoing H. pylori eradication therapy.
The Delphi method was employed. An eight-expert panel voted on 13 previously developed statements until agreement of >67% was reached. The level of supporting evidence and strength of each statement was rated using the GRADE system.
Collectively, the 70 studies investigated a total of 54 different probiotic products (containing 108 strains either alone or in combination) at doses ranging from 1×106 to 4.5×1011 colony forming units (CFU) per day, administered as one, two or three doses. They predominantly contained bacteria (mostly lactobacilli and/or bifidobacteria); a few contained the yeast Saccharomyces.
With a grade of evidence for effect being “high”, specific probiotics may help relieve overall symptom burden in some patients with IBS. Among 15 studies that evaluated overall symptoms as a primary endpoint in patients with IBS, 8 studies reported a significant beneficial effect of 8 different probiotic products (dosed at 3.4 x 107 to 2.5 x 1010 CFU per day) compared with placebo. However, the grade of evidence for the use of specific probiotics in relieving overall symptom burden in patients with constipation-predominant IBS and patients with diarrhoea-predominant IBS was very low and low, respectively.
Regarding abdominal pain, among 9 studies that evaluated abdominal pain as a primary endpoint, 7 studies showed a significant beneficial effect of specific probiotic treatments compared with placebo in some patients with IBS with a high grade of evidence.
On the other hand, probiotics showed a moderate grade of evidence in reducing bloating/distension in some patients with IBS. The role of probiotics in reducing flatus in patients with IBS is still unclear.
Although probiotics showed a moderate grade of evidence for improving frequency and/or consistency of bowel habits in some patients with IBS, its role for relief of constipation had low evidence.
In patients receiving antibiotic therapy or H. pylori eradication therapy, specific probiotics at doses of between 2 x 106 to 2 x 1010 CFU per day appeared helpful as adjuvant therapies to prevent or reduce the duration of associated diarrhoea, with a high grade of evidence. Based on 13 studies of 10 different probiotics in 6091 patients who received antibiotics, probiotics were helpful as adjuvant therapy to prevent or reduce the duration of antibiotic-associated diarrhoea.
Regarding adverse events, probiotics have a favourable safety profile in patients with a range of lower GI symptoms typically managed in primary care.
The following table summarizes practical implications of the consensus statement for healthcare practitioners:
|Grade of evidence for effect||Indications||Clinical translation|
|High||Overall symptoms and abdominal pain in IBS.|
Prevention or reduction of diarrhoea in patients receiving antibiotics or Helicobacter pylori eradication therapy.
|Probiotics should be tried.|
|Moderate||Bowel movements and bloating and distension in IBS.||Probiotics could be tried.|
|Low||Overall symptoms in IBS-D.|
Flatus in IBS.
Constipation in IBS.
|Probiotics could be considered.|
|Very low||Overall symptoms in IBS-C.|
Diarrhoea in IBS.
Table adapted from the original article (see reference in the end).
In conclusion, this updated review indicates that specific probiotics are beneficial in relieving lower GI symptoms in IBS and preventing diarrhoea in patients prescribed antibiotics or H. pylori eradication therapy.
The expert consensus panel concluded the review with the following pragmatic recommendations for clinicians:
- Specific probiotics have a role in the management of IBS in some cases and can also be used as an adjunct to conventional treatment.
- Probiotic strains should be selected based on the patient’s symptoms, the clinical indication and the available evidence; no probiotic alleviates the full range of symptoms in IBS.
- When trying a probiotic therapy for a chronic GI problem, the product should be taken at least for 1 month; dose selection should be based on available evidence and manufacturers’ recommendations.
Hungin APS, Mitchell CR, Whorwell P, et al.; for the European Society for Primary Care Gastroenterology. Systematic review and consensus: probiotics in the management of lower gastrointestinal symptoms in clinical practice – an updated evidence-based international guide. Aliment Pharmacol Ther. 2018; 00:1-17. doi: 10.1111/apt.14539.