Probiotics
Table 1: Summary of Key Randomized Controlled Trials of Probiotics in Irritable Bowel Syndrome Probiotic(s)
Reference
VSL#3 VSL#3 SCM-III
Multispecies probiotic Multispecies probiotic Lactobacillus acidophilus Lactobacillus casei GG Lactobacillus plantarum
Lactobacillus plantarum Lactobacillus plantarum Lactobacillus reuteri Lactobacillus salivarius,
Bifidobacterium infantis 35624 Bifidobacterium infantis 35624 Whorwell et al.80 Bifidobacterium animalis Guyonnet et al.81 HRQoL = health-related quality of life; IBS = irritable bowel syndrome. Effect on Visceral Hypersensitivity
Visceral hypersensitivity, where patients show a lower threshold for discomfort compared with healthy controls, is a frequent finding among patients with IBS and is regarded as a key mechanism of symptom development.56
The mechanisms responsible for the initial
increases in visceral hypersensitivity are not completely understood but evidence suggests that inflammation in the gut can cause visceral hypersensitivity.42
In this context the anti-inflammatory actions
of probiotics may be able to reverse the processes involved in immune-mediated visceral hypersensitivity. Indeed, data from experimental models support an effect of probiotics on visceral hypersensitivity through anti-inflammatory or barrier-enhancing effects.57,58
Verdu and colleagues found that the administration of
Lactobacillus paracasei attenuated antibiotic-induced visceral hypersensitivity in mice and normalized the inflammatory cell activity associated with these changes.57
In a separate study, Escherichia coli Nissle 1917 was shown to significantly reduce visceral hypersensitivity associated with inflammation in a rat model of colitis.59
The positive effects of L. farciminis treatment on
stress-induced hypersensitivity to colorectal distension have been linked to the effects of this probiotic on colonic paracellular permeability.58
Distinct from the anti-inflammatory actions of probiotics, a different mode of action of probiotics in the setting of visceral hypersensitivity was recently proposed by Rousseaux and colleagues, who demonstrated that Lactobacillus strains induced the expression of µ-opioid and cannabinoid receptors in rat intestinal epithelial cells, inhibiting visceral sensation in a manner similar to the effects of morphine.60
Finally, B.
infantis 35624 was effective at reducing visceral pain in rat models of visceral hypersensitivity, although the means by which this probiotic elicited this effect is not known.61
50 Combination Probiotics
Two studies performed by Kim et al. have assessed the effectiveness of VSL#3 for treating IBS symptoms.69,70
The first study evaluated the effect US GASTROENTEROLOGY & HEPATOLOGY REVIEW Impact on the Effects of Stress
Stressful life events are a risk factor for the triggering of IBS symptoms.62 In animal models, stress induces mucosal dysfunction via increased epithelial ion secretion and permeability, enhances the binding of luminal bacteria to surface epithelia, increases the uptake of luminal antigens through follicle associated epithelium, and initiates mucosal inflammation.63–65
Stress-induced increases in gut permeability and
visceral hypersensitivity in mice were inhibited by L. paracasei.66 Furthermore, Lactobacillus spp. were shown to reduce stress-induced bacterial translocation to the mesenteric lymph nodes of rats.67 Stress-induced increases in visceral hypersensitivity were shown to be accompanied by increased expression of Fos protein, a marker of general neuronal activation, in spinal and supraspinal sites in rats and these increases were attenuated following treatment with L. farciminis.68
Clinical Efficacy of Probiotics in Irritable Bowel Syndrome
An increasing number of RCTs have evaluated the efficacy of probiotics in patients with IBS. Unfortunately, many of the available studies are encumbered by methodologic limitations such as small sample sizes, lack of adequate blinding, short study duration, use of non-validated study end-points, and failure to report an intention-to-treat analysis. Furthermore, results between studies are difficult to compare owing to variations in design, probiotic dose, and strain and results from these trials should therefore be interpreted with some caution. Nevertheless, some positive results have been noted. Overall, studies have typically included strains of Lactobacillus species or Bifidobacterium species, along with different probiotic combinations such as VSL#3 and SCM-III (see Table 1).
4 6 362 274
Kim et al.69 Kim et al.70
Tsuchiya et al.71 Kajander et al.72 Kajander et al.73 Halpern et al.74
O’Sullivan and O’Morain75 Niedzielin et al.76
Nobaek et al.28 Sen et al.31 Niv et al.77
O’Mahony et al.44
Treatment Duration (Weeks)
8
4–8 12 24 20 6
20 4
4 4
24 8
Number of Patients
25 48 68
103 86 29 25 40
60 12 54 77
Results
Bloating decreased Flatulence decreased
Improvement in overall efficacy at 12 weeks Improved composite IBS symptom score Improved composite IBS symptom score Improved cumulative IBS symptom scores Negative
Decreased abdominal pain; improved all IBS symptoms
Decreased abdominal pain and flatulence Negative Negative
Improvement in all IBS symptoms in patients treated
with B. infantis 35624; no effect versus placebo for L. salivarius
Improvement in all IBS symptoms; global assessment >20% gain over placebo
Improved HRQoL and stool frequency; decreased bloating
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