Effects of Lactobacillus casei sppShirota on gastrointestinal symptoms AND fermentation patterns in patients with IBSand early rise in breath hydrogen after lactulose: a randomised, placebo-controlled trial.

Background:Although probiotics hold promise in correctingalterations of microbiota in patients with functional bowel disorders (FBD), clinicaltrials have yielded varyingsuccess and predictive factors that enable better targeting of therapy have not been defined. A pilot study(Barrett et al. World J Gastro 2008) demonstrated that administration of Lactobacillus caseisppShirota (LcS) may correct early rise in breath hydrogen after lactulose (ERBHAL) with improved symptoms in patients with irritable bowel syndrome (IBS).

Aims: To determine ifLcStherapy specifically modifies gut symptoms andfermentation patterns in patients with IBSand ERBHAL, and to examine its effect on gastric emptying and fructose absorption.

Methods:Patients with IBS (Rome III) and ERBHAL undertook a double-blind, randomised trial ofeither 6.5 x 109cfu(one bottle) LcSor placebo. This was followed by open-label LcStherapy and withdrawal phase,all phases being six-weeks in duration. Breath hydrogen responses to lactulose (15 g) and, in some patients, fructose (35 g) were evaluated before and at the end of each study phase. Gastric emptying half-times (t½),wereassessed simultaneously using breath 13CO2 production after ingesting 13C-acetate. Gastrointestinal symptoms were measured using a 100 mm visual analogue scale (VAS). Treatment adherence and adverse events were also documented.

Results: 45 IBS patients (23 LcS, 22 placebo) completed the double-blinded phase with an adherence rate ≥80%.Loss of ERBHAL occurred in similar proportions of LcS- (38%) and placebo-treated patients (44%). No significant changes were found between treatment arms for symptoms (Table 1), mean half-emptying times, t½(LcS2.9±3.1vs placebo 1.8±4.5 mins;p=0.85, t-test) and proportion with complete fructose absorption(27% vs 33%). In 40 patients completing open-label therapy, patterns of ERBHAL losswere similar between thosereceiving 12- vs 6 weeks of LcS(33% vs 42%; p=0.85). Of the symptoms assessed, only stool satisfaction improved in patientshaving 12-weeks ofLcS(median IQR:28[17-36]mmvs week 6(43[30-51] mm; p=0.03, Wilcoxon signed ranks). Complete fructose absorption occurred in similar proportions of patients receiving 12 vs 6 weeks of LcS (0.67; chi-square). No differences in the prevalence of ERBHAL, overall and individual symptoms, or loss of fructose malabsorption were seen after LcSwithdrawal in all patients. Overall symptom changes were not associated with the loss or continuation of ERBHAL for all study phases (p>0.05). No serious adverse events were recorded in both treatment arms.

Change in VAS / Overall symptoms1 / Abdominal pain1 / Bloating1 / Wind1 / Stool satisfaction1
LcS / Placebo / LcS / Placebo / LcS / Placebo / LcS / Placebo / LcS / Placebo
Double-blind / -11[-27, 10]2 / 0[-13, 14] / -11[-22, 25] / 2[-13, 11] / -5[-19,18] / -3[-18, -16] / -11 [-18, 8] / -3[-18 to 4] / -10[-23, 15] / -4[-21, 24]
Open-label / 0[-27, 10] / 2[-10, 8] / -9[-35, 12] / -1[-22, 19] / 0[-22, 16] / -2[17, 10] / 0[-19,17] / -1[-22, 8] / -7[-27, 9] / -1[-31, 20]

1Mann-whitney comparison between treatment arms; p = NS for all comparisons. 2 median [IQR]

Conclusions:Therapy withLcSdid not modify abdominal symptoms in patients,alter fermentation patterns, or change gastric emptying rate or fructose absorption capacity with IBS and ERBHAL.The presence of ERBHALin patients with IBS is not useful to predict response to probiotic therapy.