What is the therapeutic mechanism of the probiotics in irritable bowel syndrome patients with visceral hypersensitivity?

Abstract

Irritable bowel syndrome (IBS) is characterized by heterogeneous pathogenesis and many IBS patients suffer from visceral hypersensitivity. Visceral hypersensitivity is evaluated under stimulated condition with mechanical distension using barostat to provide sensations of discomfort or visceral pain in most clinical researches. Distensions administered to rectum using the barostat, can induce visceral discomfort or pain, which are like typical symptoms for IBS. In addition, increased rectal sensitivity has found to be related to symptom severity in daily life. It is known that visceral hypersensitivity was associated with increased intestinal permeability and inflammation. Increased intestinal permeability leads to translocation of bacteria and their products, resulting to induce hypersensitivity by targeting the enteric neurons. Increased release of immunologic mediators resulted in visceral hypersensitivity via sensitization of neuronal cells. Previous studies with probiotic therapeutic effects have focus on daily symptoms in IBS patients, and the effects were a small but significant improvement in overall symptom score. However, in previous studies, heterogeneous groups of IBS patients have been included rather than a selection of IBS patients based on pathophysiological characteristics. None of the studies up to now has chosen an approach by evaluating effects of probiotics targeting on one common pathophysiological mechanism. In this study, Ludidi et al1 investigated that whether implementing probiotics in IBS patients with documented visceral hypersensitivity had potential effect to reduce visceral hypersensitivity (primary end point). This study was performed a randomized, placebo-controlled, double-blind trial in 40 Rome III IBS patients with visceral hypersensitivity. Prior to participation, patients kept a 2-weak symptom diary and underwent barostat measurement. When visceral hypersensitivity was confirmed, patients were enrolled this study and received a multispecies probiotics (6 different probiotic strains 109 CFU/g), or a placebo products of one sachet (5 g) per day for 6 weeks. At the end of the intervention period, visceroperception and symptoms were reevaluated. In total, 35 patients were completed the study (19 in probiotics and 16 in placebo groups). At baseline, all included patients showed visceral hypersensitivity, but the percentage of hypersensitive patients decreased significantly within both the probiotics and placebo groups after 6 weeks of intervention (toward 76.5% and 71.4%, respectively; both P < 0.05 vs. baseline). However, response rates did not differ between the probiotic and placebo groups (P = 0.24). In addition, median thresholds for pain, urge and discomfort did not differ significantly before vs. after intervention within the probiotic nor the placebo group. The difference in first sensation to rectal distension was not significant between probiotic vs. placebo group (0.00 [−0.17 to 15.00] vs. 0.00 [−17.00 to 23.00]; P = 0. 78). Mean symptom improvement was not significantly different between probiotic vs. placebo group (19% vs. 39%, P = 0.18), but interestingly there were gender-related response differences in the placebo group. In placebo group, bloating, abdominal cramping and symptom-free days only improved in the female patients, but not in the male patients. However, this gender-difference was not observed in the probiotic group. The authors concluded that in targeted subgroups of IBS patients with a common pathophysiological characteristics (documented visceral hypersensitivity), no significant effect of a multi-species probiotic on visceroperception was observed.