Filippo Cremonini

The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review

Introduction Probiotics may benefit irritable bowel syndrome (IBS) symptoms, but randomised controlled trials (RCTs) have been conflicting; therefore a systematic review was conducted. Methods MEDLINE (1966 to May 2008), EMBASE (1988 to May 2008) and the Cochrane Controlled Trials Register (2008) electronic databases were searched, as were abstracts from DDW (Digestive Diseases Week) and UEGW (United European Gastroenterology Week), and authors were contacted for extra information. Only parallel group RCTs with at least 1 week of treatment comparing probiotics with placebo or no treatment in adults with IBS according to any acceptable definition were included. Studies had to provide improvement in abdominal pain or global IBS symptoms as an outcome. Eligibility assessment and data extraction were performed by two independent researchers. Data were synthesised using relative risk (RR) of symptoms not improving for dichotomous data and standardised mean difference (SMD) for continuous data using random effects models. Results 19 RCTs (18 papers) in 1650 patients with IBS were identified. Trial quality was generally good, with nine reporting adequate methods of randomisation and six a method of concealment of allocation. There were 10 RCTs involving 918 patients providing outcomes as a dichotomous variable. Probiotics were statistically significantly better than placebo (RR of IBS not improving=0.71; 95% CI 0.57 to 0.88) with a number needed to treat (NNT)=4 (95% CI 3 to 12.5). There was significant heterogeneity (χ2=28.3, p=0.001, I2=68%) and possible funnel plot asymmetry. Fifteen trials assessing 1351 patients reported on improvement in IBS score as a continuous outcome (SMD=−0.34; 95% CI −0.60 to −0.07). There was statistically significant heterogeneity (χ2=67.04, p<0.001, I2=79%), but this was explained by one outlying trial. Conclusion Probiotics appear to be efficacious in IBS, but the magnitude of benefit and the most effective species and strain are uncertain.

Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis

Aminosalicylates are the mainstay of therapy to prevent relapse of quiescent ulcerative colitis. The rationale for using probiotics is based on the evidence implicating intestinal bacteria in the pathogenesis of this disorder.

Effect of different probiotic preparations on anti-helicobacter pylori therapy-related side effects: a parallel group, triple blind, placebo-controlled study

OBJECTIVES:Several studies show that probiotics may prevent side effects during therapy against Helicobacter pylori (H. pylori). Other reports indicate competitive interaction between some probiotics and H. pylori. We compared efficacy of two different probiotics and one probiotic combination with placebo for preventing anti-H. pylori therapy-related side effects and for improving the eradication rate.METHODS:A total of 85 H. pylori positive, asymptomatic patients were randomized in four groups to receive probiotic or placebo both during and for 7 days after a 1-wk triple therapy scheme (rabeprazole 20 mg b.i.d., clarithromycin 500 mg b.i.d., and tinidazole 500 mg b.i.d.). Group I (n = 21) received Lactobacillus GG; group II (n = 22), Saccharomyces boulardii; group III (n = 21), a combination of Lactobacillus spp. and biphidobacteria; and group IV (n = 21), placebo. Subjects filled in weekly symptom questionnaires for 4 wk. Blinded investigators collected and analyzed data. H. pylori status was rechecked after 5–7 wk.RESULTS:Side effects occurred mainly during the eradication week. None of them caused therapy discontinuation. In all probiotic-supplemented groups, there was a significantly lower incidence of diarrhea and taste disturbance during the eradication week with respect to the placebo group. Overall assessment of tolerability was significantly better in the actively treated patients than in the placebo group. No differences in the incidence of side effects between the probiotic groups were observed. The H. pylori eradication rate was almost identical between the probiotic and placebo groups.CONCLUSIONS:All the probiotics used were superior to placebo for side effect prevention, but were not associated with better compliance with antibiotic therapy. The effect of probiotic supplementation on side effects during anti-H. pylori regimens seemed to be independent of the probiotic species used.

The effect of oral administration of Lactobacillus GG on antibiotic‐associated gastrointestinal side‐effects during Helicobacter pylori eradication therapy

One‐week triple therapy is currently considered the golden standard against Helicobacter pylori. However, gastrointestinal side‐effects are among the major pitfalls in such regimens. Probiotic supplementation might help to prevent or reduce such drug‐related manifestations.

Efficacy of alosetron in irritable bowel syndrome: a meta-analysis of randomized controlled trials

Abstract The 5HT3 receptor antagonist alosetron has been tested in several trials on irritable bowel syndrome (IBS) patients. The aim of the present meta‐analysis was to determine its effect on adequate relief of pain or global improvement of symptoms in IBS patients. Six large, multicentre, randomized, placebo‐controlled trials fulfilled pre‐set criteria for high quality and were included in the meta‐analysis; 1762 patients were randomized to alosetron treatment and 1356 to placebo. Seventy‐five per cent of the patients experienced diarrhoea‐predominant IBS and 93% were females. The pooled odds ratio for adequate relief of pain or global symptoms improvement was 1.81 [95% confidence interval (CI) 1.57–2.10). The average number of patients needed to treat with alosetron for one patient to achieve improvement over placebo treatment was seven (95% CI 5.74–9.43). The present analysis shows that alosetron 1 mg b.i.d. positively impacts global symptoms, and pain and discomfort in non‐constipated IBS female patients. One in four patients treated with alosetron may develop constipation. The efficacy of alosetron is unclear in male patients.

A lyophilized and inactivated culture of Lactobacillus acidophilus increases Helicobacter pylori eradication rates

Acid suppression plus two antibiotics is considered the reference anti‐Helicobacter pylori treatment. Reported eradication rates are around 65–80%. Human Lactobacillus acidophilus shows an in vitro inhibitory effect on the attachment of H. pylori to gastric epithelial cell lines. Culture supernatant of this bacillus seems to decrease the in vitro viability of H. pylori.

Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth.

Background : Small intestinal bacterial overgrowth and sugar malabsorption (lactose, fructose, sorbitol) may play a role in irritable bowel syndrome. The lactulose breath test is a reliable and non‐invasive test for the diagnosis of small intestinal bacterial overgrowth. The lactose, fructose and sorbitol hydrogen breath tests are widely used to detect specific sugar malabsorption.

Performance characteristics of scintigraphic transit measurements for studies of experimental therapies.

Background : The intra‐ and inter‐individual reproducibility of gastrointestinal and colonic transit tests require full characterization.

Association of distinct α2 adrenoceptor and serotonin transporter polymorphisms with constipation and somatic symptoms in functional gastrointestinal disorders

Background: The role of genetics in the phenotypic manifestations of irritable bowel syndrome (IBS) is unclear. Our aims were: (1) to compare the prevalence of polymorphisms of alpha 2 (α2) adrenoceptors, norepinephrine transporter, and serotonin transporter protein (soluble carrier protein member 4 (SLC6A4)) promoter in patients with lower functional gastrointestinal disorders (FGID) and in healthy controls; and (2) to test associations of these genetic variations with symptoms of IBS and high somatic symptom scores. Methods: Validated bowel and somatic symptom questionnaires characterised the phenotype: 90 with IBS constipation (IBS-C), 128 IBS diarrhoea, 38 IBS alternating bowel function, and 20 chronic abdominal pain. Logistic regression analyses assessed associations of different polymorphisms for α2 adrenoceptor and SLC6A4 with IBS or chronic abdominal pain phenotypes and high somatic score. Results: Two distinct polymorphisms independently appeared to be associated with the phenotype IBS-C: α2C Del 322–325 (odds ratio (OR) 2.48 (95% confidence interval (CI) 0.98, 6.28); p = 0.05) and α2A −1291 (C→G) (OR 1.66 (95% CI 0.94, 2.92); p = 0.08) relative to wild-type. Overall, the α2C Del 322–325 polymorphism (alone or combined with other polymorphisms) was also significantly associated with a high somatic symptom score (OR 2.2 (95% CI 1.06, 4.64); p = 0.03). Combinations of polymorphisms were also associated with high somatic scores. Conclusion: Functionally distinct α2A and α2C adrenoceptor and serotonin transporter polymorphisms are associated with constipation and high somatic symptoms in patients with lower functional gastrointestinal disorders, although the strength of the genetic contribution to the phenotype is unclear.

Opioids and the gut: pharmacology and current clinical experience

Abstract  This article reviews the pharmacology and physiology of opiate receptors and the current and potential uses of opioid agonists and antagonists in clinical gastroenterology. μ‐receptors are involved in motor and sensory functions, and their modulation is established for treatment of diarrhea. μ‐antagonists have potential to reverse endogenous (e.g., postoperative ileus) or iatrogenic dysmotility (e.g., opioid bowel dysfunction). Modulation of the function of κ‐receptors may be a novel approach to control visceral pain in functional gut disorders. Results of formal testing of novel opioid modulators are keenly awaited.