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Probiotics in the Treatment of Irritable Bowel Syndrome

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - Canadian Digestive Disease Week (CDDW) and the Annual CASL Winter Meeting

Victoria, B.C. / March 1-4, 2013

Victoria - Irritable bowel syndrome (IBS) is a persistent condition of uncertain etiology, for which definitive treatments are lacking. Some traditional therapies, such as increasing dietary fibre, are not supported by recent clinical data. Recent research into microbiota has shown potential causative links between IBS and intestinal biofilm disturbances such as those caused by bowel infections. Here at CDDW clinical findings concerning probiotics, the potential anti-inflammatory effects derived from specific bacterial strains via immunomodulation, and their beneficial effects on IBS symptoms were presented.

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

Irritable bowel syndrome (IBS) is a functional bowel disorder of uncertain etiology with an estimated prevalence of 10% to 15% in North America. In a study of 877 patients with IBS using the self-reporting SF-36 Health Survey, IBS was identified as reducing quality of life to a greater extent than gastroesophageal reflux disease, diabetes mellitus and dialysis-dependent end-stage renal disease (Gralnek et al. Gastroenterology 2000;119(3):654-60).

A Multi-faceted Syndrome

Management of IBS can be difficult and evidence for effective treatment of the condition is sparse. The World Gastroenterology Organization (WGO) guidelines for IBS management recognizes an association between diet and IBS, but notes a lack of evidence that dietary modification, such as regular mealtimes and the addition of fibre to the diet, improves IBS symptoms (WGO practice guideline—irritable bowel syndrome: a global perspective. 2009. At: Accessed March 4, 2013).

A recent Cochrane Database review found that fibre is ineffective in IBS, but that antispasmodics and antidepressants are helpful (Ruepert et al. Cochrane Database Syst Rev 2011;10;(8):CD003460). The guidelines do acknowledge the importance of stress reduction and importance of addressing psychological factors.

Strain-specific Effects of Probiotics

The WGO guidelines acknowledge the role of probiotic therapy in treating IBS symptoms, emphasizing the strain-specific nature of the effects. Probiotic therapy is often used to restore biodiversity to the gut flora following an event that has reduced bacterial diversity, such as the use of a broad-spectrum antibiotic or the consumption of heavily contaminated food or water.

Prof. Fergus Shanahan, University College Cork, Ireland, explained that low microbiotic diversity is an unstable situation that presents an opportunity for pathogens to become established. In these circumstances, the goal is to restore diversity and the specificity of bacterial strains used in a probiotic or a fecal transplant may be of less importance than the need to rapidly re-establish a healthy microbiota. However, if the goal of therapy is to produce a specific effect, such as an anti-inflammatory response, then the choice of bacterial strain may also need to be highly specific, in order to affect only the required pathways.

The ability of select probiotic strain to produce a specific beneficial effect has been demonstrated in a number of studies, including an investigation using mice in which Lactobacillus salivarius UCC118 was shown to be protective against Listeria monocytogenes infection via the production of the proteinaceous toxin bacteriocin Abp118. (Corr et al. Proc Natl Acad Sci USA 2007;104(18):7617-21).

Findings such as this underscore the importance of recognizing that probiotics should not be regarded as agents that are essentially similar to one another. “If you are taking [a medication] for high blood pressure, cholesterol or an infection, you would not just take a tablet”, remarked Prof. Shanahan, “You would want to know what’s in the tablet, and that it is matched for the desired function. The same is true of probiotics.”

IBS and Cytokine Expression

Referring to a recent study, (Jeffery et al. Gut 2012;61(7):997-1006.) Prof. Shanahan noted that IBS is associated with changes in the composition of the gut microbiota and that there are coincident changes in the expression of the immuno-inflammatory Toll-like receptor 4 (TLR4). IBS is known to be accompanied by low-grade inflammation, with changes in mast cell numbers, cytokines and T-cell activation, although not in neutrophils, which do increase in inflammatory bowel disease.

Prof. Shanahan described the research progam that his group has undertaken to isolate and screen bacterial strains with potentially beneficial characteristics for human use. Some 1500 strains of mucosal adherent bacteria originating from the human gut were initially cultured and purified. The cultures were then tested for resistance to acid and bile, then screened in vitro and in vivo for activity against pathogens such as Salmonella spp (while themselves lacking in pathogenicity), as well as for changes in mucosal immune function. Viable transit of the strains through the gut was verified by examination of stool samples from subjects following consumption of the test strains. One strain of interest that emerged from this screening process was Bifidobacterium infantis 35624. Prof. Shanahan reviewed data from a recent study on human volunteers that suggested that the B. infantis 35624 strain elicits low-level induction of Foxp3 T-cells and also increases IL-10, further evidence of an immune anti-inflammatory mechanism for the effects of this probiotic (Konieczna et al. Gut 2012;61(3):354-66.)

Suspicion that the B. infantis probiotic reduces pro-inflammatory cytokines has been confirmed in investigations of patients with psoriasis, chronic fatigue syndrome and ulcerative colitis, Prof. Shanahan revealed. Data from a paper by Groeger et al. (in preparation) demonstrates significant reductions in tumour necrosis factor and C-reactive protein in these patients.

Efficacy Studies

IBS is a heterogeneous condition, and the mechanisms by which symptoms are produced are uncertain. It is therefore difficult to determine what effect is needed to produce symptomatic relief among such possibilities as an anti-inflammatory effect, reduced visceral hypersensitivity, analgesia or modulation of resident microbiota. Based on this, and on the properties of probiotics discussed previously, Prof. Shanahan noted that as a treatment for IBS, probiotics would be expected to have modest efficacy, and that not all probiotics would be expected to show benefits. However, probiotics have a long safety record, he confirmed, adding “I worry more about potential side effects or lack of safety from a contaminant, than about the active ingredient.” To ensure quality control, Prof. Shanahan recommended that those who use probiotics acquire them from a reputable source.

In a rare head-to-head, randomized double-blind placebo-controlled study of ingested daily 1010 doses of L. salivarius UCC4331 or B. infantis 35624, the response of IBS symptoms and cytokine ratios were compared in 75 IBS patients for 8 weeks. The subjects were followed for 12 weeks (O’Mahony et al. Gastroenterology 2005;128(3):541-51). Patients randomized to B infantis experienced a significantly greater reduction in composite and individual symptom scores for abdominal pain/discomfort, bloating/distension and bowel movement difficulty than those on placebo (P<0.05), for most weeks during the treatment phase. Patients taking L. salivarius did not improve their scores compared to placebo. The effect was lost when treatment ended. “When you give probiotics to adults, most people don’t colonize,” stated Prof. Shanahan, “and you have to continue with the probiotic. You will get colonization in younger people.”

At baseline, patients with IBS demonstrated a significantly abnormal ratio of IL-10:IL-12 proinflammatory markers compared to controls. This ratio was normalized for patients in the B. infantis arm only, suggesting an immune-modulating role for this organism in IBS.

Whorwell and colleagues performed a larger, dose-ranging study of B. infantis 35624 in 362 females with IBS in primary care centres (Am J Gastroenterol 2006;101(7):1581-90). Composite and abdominal pain/discomfort scores were significantly lower (P=0.013 and P=0.023, respectively) at the end of 4 weeks in the group using a 108 daily dose than in the 106  dose or placebo arms, as was global assessment of relief (P=0.0118). A 1010 dose arm was ineffective due to formulation problems.

A number of systematic reviews have demonstrated overall beneficial effects from probiotics in IBS. Although these reviews did not distinguish between individual probiotic strains, they nevertheless showed modest benefits from treatment. (McFarland LV, Dublin S. World J Gastroenterol 2008;14(17):2650-61; Nikfar et al. Dis Colon Rectum 2008;51(12):1775-80.) In one analysis, the number needed to treat was only 4. “This is remarkably good, considering we don’t even have drugs for IBS that can do as well as this,” commented Prof. Shanahan, emphasizing that probiotics should not be considered substitutes for conventional treatment.

In a systematic review of studies of individual probiotic strains in the treatment of IBS by Brenner and co-workers, of 16 randomized, controlled trials evaluating probiotics, B. Infantis 35624 was the only strain to show significant improvements in IBS symptoms in an appropriately designed study (Am J Gastroenterol 2009;104:1033-49).


Emerging evidence is clarifying the nature of the effects of probiotics and their mechanisms of action. Specific strains are capable of producing modest but well-defined effects. These effects are produced, not simply locally within the gut, but in some cases by immunomodulation resulting in regulation, normalization of inflammatory pathways and improved quality of life.

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