Efficacy and Safety of Probiotics in the Treatment of Irritable Bowel Syndrome
probiotics for IBS symptom improvement and this article will also consider the evidence base for probiotic use in this setting.
Rationale for the Use of Probiotics in Irritable Bowel Syndrome
Of the purported contributors to the pathogenesis of IBS, factors with the greatest potential relevance to probiotics include alterations in luminal microflora, mucosal immune activation, alterations in visceral hypersensitivity, and stress-induced mucosal dysfunction.
Modification of Intestinal Microflora
There is now substantial evidence suggesting that alterations in GI microflora may play a role in the pathogenesis of IBS in a proportion of patients.13
Abnormalities in GI microflora could arise secondary to alterations in substrate availability owing to dietary abnormalities,18,19 following episodes of bacterial gastroenteritis,8 broad-spectrum antibiotic use.20
or as a consequence of Enhancement of the Immune Response
More recent studies using polymerase chain reaction (PCR)-based approaches have demonstrated a greater instability in intestinal microbiota in IBS patients compared with healthy controls23 and preliminary investigations have noted variations in microflora composition according to the IBS symptoms reported. For example, fecal samples from diarrhea-predominant IBS patients showed lower numbers of Lactobacilli spp. and increased amounts of the anaerobic bacteria Veillonella spp. and methane-producing bacteria have been noted in constipation-predominant IBS patients.24,25
However,
tremendous intra-individual variability has been observed and many of these studies were performed on small numbers of patients, rendering these findings far from conclusive. Nevertheless, these provocative preliminary results warrant further investigation.
Qualitative changes in colonic microflora could lead to the proliferation of species that produce altered fermentation patterns and increased gas production (potentially contributing to symptoms of bloating/discomfort)26,27
and altered colonic motility and/or sensitivity.27
Treatment with probiotics could potentially alter bacterial populations within the colon, resulting in functional and sensory changes which, in turn, could lead to symptom relief. For example, certain probiotic bacteria have been shown to reduce luminal pH by producing short-chain fatty acids such as lactic acid through fermentation.28,29
The colonic
acidification observed following ingestion of L. plantarum 299v has been shown to inhibit the growth of gas-producing Clostridia spp. while increasing the numbers of fecal Bifidobacteria spp. and Lactobacillus spp., which tend not to produce gas.30
consequences of these types of observations is currently lacking.31
Quantitative changes in intestinal flora may also be important in IBS, particularly small intestinal bacterial overgrowth (SIBO), which may occur more commonly in IBS patients.32,33
Whether or not IBS patients
have a higher likelihood of SIBO remains controversial. A recent study identified significant quantitative differences in small intestinal bacterial concentrations between IBS patients and controls. However,
US GASTROENTEROLOGY & HEPATOLOGY REVIEW
In addition, a range of probiotics including VSL#3 and L. plantarum 299v have been shown to enhance barrier function in experimental models, a property that may be relevant to the treatment of IBS.52,53
Taken
together, the results of studies such as these are interesting and promising but the majority, to date, have been conducted in animal models and these results require further investigation and confirmation in IBS patients.
49
Early studies using conventional microbiologic techniques suggested the presence of qualitative changes in the colonic flora in IBS patients, most frequently in the form of decreased fecal Lactobacilli and Bifidobacteria.21,22
The importance of previous or sustained mucosal immune activation in the development of IBS symptoms has become evident in recent years12 and evidence suggesting an association between immunologic alterations in the gut and post-infectious IBS as well as IBS not preceded by a GI infection is accumulating.40,41
Subgroups of IBS patients have
low-grade inflammation within the gut wall and altered immunologic function, including increased mucosal levels and activation of mast cells42
mononuclear cells43,44
and altered cytokine profiles in peripheral blood and serum.45
These factors could play a role in the
disturbed neuroenteric and motor function observed in IBS patients. Furthermore, small intestine permeability is frequently abnormal in subsets of IBS patients,46
potentially exposing the mucosa to luminal
antigens (dietary and bacterial) and this may play a role in promoting and maintaining mucosal immune activation.
The benefit seen with probiotics in inflammatory bowel disease patients with pouchitis17
provides a rationale for the use of these agents in the subset of IBS patients with mucosal inflammation. Various probiotics have been shown to inhibit inflammatory responses in animal models of colitis via immunomodulatory effects47-51 function.52,53
or effects on epithelial barrier For example, the probiotic mixture VSL#3 (a mixture of
several Lactobacillus and Bifidobacteria species together with Streptococcus thermophilus) was shown to stimulate regulatory T cells, exerting an anti-inflammatory effect and ameliorating the severity of recurrent colitis in an experimental model.47
The same probiotic mixture
was shown to be a potent inducer of the anti-inflammatory cytokine interleukin (IL)-10 and suppressor of the pro-inflammatory cytokine IL-12 in human dendritic cells.48
However, proof of the practical The same study indicated that the most
marked anti-inflammatory effects were produced by Bifidobacteria strains and the immunomodulatory effects of B. infantis 35624 have been demonstrated in subsequent studies.43,54,55
the level of bacterial contamination in the small bowel of IBS patients did not rise to the level of the formal definition for SIBO (>105 colony- forming unit [CFU]/ml of jejunal aspirate).34
There are now robust data
to suggest that treatment with the non-absorbable antibiotic rifaximin improves IBS symptoms in the short term.35
It remains unclear whether
these clinical benefits are the result of reduction/modification of intestinal or colonic flora, or both. Whether probiotics can improve or prevent SIBO remains untested.
Certain probiotics possess anti-pathogenic properties either through the production of antibacterial compounds, termed bacteriocins, or through the inhibition of pathogen binding to epithelial cells.36–39
Such
properties could potentially contribute to the beneficial activity of probiotics in IBS, particularly in the context of post-infectious IBS following bacterial gastroenteritis.8
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