Irritable bowel syndrome

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Irritable bowel syndrome (IBS) is a widespread functional gastrointestinal disorder that affects 10-20% of the Western population (Drossman et al., 2002). The main clinical features of IBS include abdominal pain, bloating, flatulence and variable bowel habit. Current treatments for IBS are regarded as relatively ineffective. The pathophysiology of IBS remains unknown, but there is evidence that at least in part of the patients an imbalanced intestinal microbiota is associated with the onset of disease.

4.4.1 The role of the intestinal microbiota in IBS

Studies comparing IBS patients with healthy control subjects show that the intestinal microbiota may be aberrant in IBS. The composition of the microbiota has been investigated both using conventional culturing methods and by DNA-based techniques. Indirect methods studying the metabolic activity of the microbiota have also been applied. Early studies by Balsari and colleagues (Balsari et al., 1982) found that IBS patients had significantly lower numbers of coliforms, lactobacilli and bifidobacteria. Another study based on culturing methods produced a similar finding regarding lower numbers of bifidobacteria in IBS patients (Si et al., 2004). In addition to lower numbers of bifidobacteria, an increase in Enterobacteriaceae was also observed. In contrast to Balsari et al. (1982), a recent study found a slightly higher number of coliforms in IBS (Mättö et al., 2005). No differences were found in the mean culturable numbers of bacteroides, bifidobacteria, spore-forming bacteria, lactobacilli, enterococci or yeasts, but an increased aerobe: anaerobe ratio could be seen.

Extensive culturing-independent quantitative PCR analysis has revealed lower amounts of Lactobacillus spp. in diarrhoea predominant IBS and higher amounts of Veillonella spp. in constipation predominant IBS when these IBS subtypes were compared to healthy controls (Malinen et al., 2005). Results also suggested a lower level of Clostridium coccoides and Bifidobacterium catenulatum in IBS. Another DNA-based method, denaturing gradient gel electrophoresis (PCR-DGGE), has shown more temporal instability in the predominant bacterial populations of IBS patients compared to healthy controls (Matto et al., 2005). The same kind of general instability of the predominant microbiota combined with changes in the clostridial population was found to be typical for IBS in a study by Maukonen et al. (2006). An increased formation of colonic hydrogen (King et al., 1998) and an abnormal pattern of short-chain fatty acids (Treem et al., 1996) in irritable bowel syndrome also indicate an imbalanced microbiota. There is thus a growing body of evidence indicating that the intestinal microbiota in IBS may differ from a healthy microbiota. It is, however, unclear whether alterations in the microbiota are a cause of IBS or a result of, for instance, disturbed gut motility induced by the syndrome.

Dietary therapy may be useful in IBS as certain foods can aggravate symptoms in some patients (Drossman et al., 2002). For instance, fatty foods, beans and other gas-producing foods, alcohol, caffeine and lactose are often mentioned as causing discomfort. Fibre is considered to have an established role in the treatment of constipation in IBS, but other forms of IBS do not benefit from added fibre.

4.4.2 Probiotics and prebiotics in irritable bowel syndrome

Indications of an aberrant microbiota in IBS have raised the hypothesis of probiotic therapy in IBS. Some intervention studies have reported improvements in IBS symptoms, while others have found probiotics to be ineffective. It should be emphasized that the quality of the trials, such as sample size and duration, vary considerably. Given the chronicity and fluctuating nature of functional gastrointestinal disorders, a minimum treatment duration of four weeks is generally recommended for short-term trials and six months for long-term efficacy evaluation (Irvine et al., 2006). With few exceptions, the vast majority of studies are of a short-term nature.

The effect of Lactobacillus plantarum 299v on IBS symptoms has been investigated in three randomized placebo-controlled trials. In a four-week trial, Nobaek and colleagues (2000) demonstrated L. plantarum 299v to be significantly more efficient than placebo in reducing flatulence and abdominal pain. A second study with the same probiotic also found a reduction in abdominal pain (Niedzielin et al., 2001), whereas a third study including only 12 patients was not able to confirm any improvement of symptoms (Sen et al., 2002). Besides L. plantarum 299v, other strains of lactobacilli have also been clinically investigated. L. rhamnosus GG administration to adults resulted in a trend towards less diarrhoea, but no other improvements could be seen (O'Sullivan and O'Morain, 2000). Neither did L. rhamnosus GG alleviate abdominal pain in children suffering from IBS (Bausserman and Michail, 2005). Also a six-month L. reuteri ATCC 55730 therapy was concluded to be ineffective (Niv et al., 2005). An early trial with L. acidophilus milk was unable to demonstrate any advantage (Newcomer et al., 1983), whereas heat-killed L. acidophilus capsules have demonstrated a therapeutic benefit (Halpern et al., 1996).

In addition to lactobacilli, other probiotics and probiotic combinations have also been studied in IBS. In an eight-week trial, B. infantis 35624 has been able to alleviate IBS symptoms, and normalize an aberrant interleukin-10/interleukin-12 ratio closer towards healthy subjects (O'Mahony et al., 2005). In the same setting, L. salivarius UCC4331 gave only mild relief to the participating IBS patients. Streptococcus faecium therapy has also demonstrated a positive effect (Gade and Thorn, 1989) in one intervention. A preparation containing L. plantarum LP01 and B. breve BR0 has also demonstrated slight improvements in a four-week controlled study (Saggioro, 2004). A probiotic combination consisting of eight different bacterial species, VSL#3, showed some favourable effects on bloating and flatulence scores in controlled settings (Kim et al., 2003, 2005), as well as in a small uncontrolled intervention (Brigidi et al., 2001). Another probiotic combination consisting of L. rhamnosus GG, L. rhamnosus Lc705, B. breve B699 and Propionibacterium freudenreichii ssp. shermanii JS was shown to be significantly superior to placebo in alleviating IBS symptoms in thus far the only six-month long-term intervention showing positive response (Kajander et al., 2005).

In conclusion, the studies available suggest that certain probiotic strains and probiotic combinations are effective in the relief of IBS. Clinical trials reporting the effect of prebiotics or synbiotics in IBS are scarce, and no recommendation can be made from them. The effects of probiotics in IBS are obviously strain-specific, and hence all strains or combinations of strains have to be studied separately in carefully designed, double-blind human interventions.

4.4.3 Possible mechanisms behind probiotic therapy in IBS

There are several putative mechanisms that could explain the reduction of IBS symptoms by probiotics. Probiotics could influence the symptoms by balancing the microbiota, and thus restoring possibly aberrant gas-production or production of short chain fatty acids. An inflammatory component has also been suggested in IBS, especially in so-called post-infectious IBS, a form of IBS that affects 10-15% of patients after acute infectious enteritis (Spiller, 2003). Many probiotics can modulate the immune system for instance by balancing the ratio between pro-inflammatory and anti-inflammatory cytokines, and could hence alleviate a possible low-grade inflammation (Blum et al., 2002; Ezendam and van Loveren, 2006). In addition to the balancing effect on the microbiota and the immunomodulatory effects, recent studies also suggest that probiotics may influence intestinal motility. In vitro studies on isolated intestines of guinea pigs have shown that probiotics, especially bifidobacteria, have a relaxing effect on the colon (Massi et al., 2004). Lactobacillus paracasei seems also to attenuate post-infective dysmotility and visceral hypersensitivity in murine models of IBS (Verdu et al., 2004 and 2006).

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