A Randomized, Double-Blind, Placebo-Controlled Trial: The Efficacy of Multispecies Probiotic Supplementation in Alleviating Symptoms of Irritable Bowel Syndrome Associated with Constipation

Abstract

Background and Aim. The efficacy of supplementation treatment with two multispecies probiotic formulates on subjects diagnosed with IBS-C and the assessment of their gut microbiota were investigated. Methods. A randomized, double-blind, three-arm parallel group trial was carried out on 150 IBS-C subjects divided into three groups (F_1, F_2, and F_3). Each group received a daily oral administration of probiotic mixtures (for 60 days) F_1 or F_2 or placebo F_3, respectively. Fecal microbiological analyses were performed by species-specific qPCR to assess the different amount of probiotics. Results. The percentage of responders for each symptom was higher in the probiotic groups when compared to placebo group during the treatment period (t60) and was maintained quite similar during the follow-up period (t90). Fecal analysis demonstrated that probiotics of the formulations increased during the times of treatment only in fecal DNA from subjects treated with F_1 and F_2 and not with F_3, and the same level was maintained during the follow-up period. Conclusions. Multispecies probiotic supplementations are effective in IBS-C subjects and induce a different assessment in the composition of intestinal microbiota. This clinical study is registered with the clinical study registration number ISRCTN15032219.

Efficacy and Safety of Probiotics in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis

“…While 19 RCTs (Kim et al, 2003;Kajander et al, 2005;Kim et al, 2005;Drouault-Holowacz et al, 2008;Sinn et al, 2008;Hong et al, 2009;Simrén et al, 2010;Guglielmetti et al, 2011;Sondergaard et al, 2011;Ducrotte et al, 2012;Kruis et al, 2012;Begtrup et al, 2013;Roberts et al, 2013; FIGURE 2 | Risk of bias. Sisson et al, 2014;Lorenzo-Zuniga et al, 2014;Pineton de Chambrun et al, 2015;Mezzasalma et al, 2016;Spiller et al, 2016;Hod et al, 2017) with low bias risk were assessed, the effect was still significant (RR = 1.59; 95% CI 1.25-2.04).…”

“…Thirty-five RCTs (Gade and Thorn, 1989;Nobaek et al, 2000;Niedzielin et al, 2001;Kim et al, 2003;Kajander et al, 2005;Kim et al, 2005;Whorwell et al, 2006;Guyonnet et al, 2007;Drouault-Holowacz et al, 2008;Enck et al, 2008;Sinn et al, 2008;Enck et al, 2009;Hong et al, 2009;Simrén et al, 2010;Guglielmetti et al, 2011;Sondergaard et al, 2011;Cha et al, 2012;Cui and Hu, 2012;Dapoigny et al, 2012;Ducrotte et al, 2012;Kruis et al, 2012;Begtrup et al, 2013;Roberts et al, 2013;Jafari et al, 2014;Lorenzo-Zuniga et al, 2014;Ludidi et al, 2014;Sisson et al, 2014;Yoon et al, 2014;Pineton de Chambrun et al, 2015;Yoon et al, 2015;Spiller et al, 2016;Mezzasalma et al, 2016;Thijssen et al, 2016;Hod et al, 2017;Sun et al, 2018) with 4,392 patients reported overall IBS symptoms improvement or response as a dichotomous outcome. There were two (Lorenzo-Zuniga et al, 2014;Mezzasalma et al, 2016) of these RCTs examining two different dose groups and one (Whorwell et al, 2006) examining three different dose groups. One (Gade and Thorn, 1989) RCT did not mention the dose of probiotics, so it was not...…”

“…In the subgroup of duration, 18 studies (Gade and Thorn, 1989;Nobaek et al, 2000;Niedzielin et al, 2001;Kim et al, 2005;Whorwell et al, 2006;Guyonnet et al, 2007;Drouault-Holowacz et al, 2008;Sinn et al, 2008;Guglielmetti et al, 2011;Cui and Hu, 2012;Dapoigny et al, 2012;Ducrotte et al, 2012;Jafari et al, 2014;Lorenzo-Zuniga et al, 2014;Ludidi et al, 2014;Yoon et al, 2014;Yoon et al, 2015;Sun et al, 2018) evaluated a shorter duration (< 8 weeks) and 17 studies (Kim et al, 2003;Kajander et al, 2005;Enck et al, 2008;Enck et al, 2009;Hong et al, 2009;Simrén et al, 2010;Sondergaard et al, 2011;Cha et al, 2012;Kruis et al, 2012;Begtrup et al, 2013;Roberts et al, 2013;Sisson et al, 2014;Pineton de Chambrun et al, 2015;Mezzasalma et al, 2016;Spiller et al, 2016;Thijssen et al, 2016;Hod et al, 2017) used a longer duration (≥ 8 weeks). The RR of group with less than 8 weeks was 1.55 (95% CI 1.27-1.89; Figure 4), and the RR of group with more than 8 weeks was 1.52 (95% CI 1.23-1.88), with significant heterogeneity (I 2 = 74%, P < 0.01; I 2 = 69%, P < 0.01, respectively).…”

“…The RR of group with less than 8 weeks was 1.55 (95% CI 1.27-1.89; Figure 4), and the RR of group with more than 8 weeks was 1.52 (95% CI 1.23-1.88), with significant heterogeneity (I 2 = 74%, P < 0.01; I 2 = 69%, P < 0.01, respectively). In the subgroup of probiotics dose, high doses (daily dose of probiotics ≥ 10 10 ) were assessed in 21 trials (Niedzielin et al, 2001;Kim et al, 2003;Kim et al, 2005;Whorwell et al, 2006;Guyonnet et al, 2007;Drouault-Holowacz et al, 2008;Hong et al, 2009;Simrén et al, 2010;Sondergaard et al, 2011;Cha et al, 2012;Ducrotte et al, 2012;Kruis et al, 2012;Begtrup et al, 2013;Roberts et al, 2013;Sisson et al, 2014;Lorenzo-Zuniga et al, 2014;Yoon et al, 2014;Yoon et al, 2015;Mezzasalma et al, 2016;Thijssen et al, 2016;Hod et al, 2017). A significant effect on symptoms (RR = 1.51; 95% CI 1.20-1.91; Figure S2) and statistically significant heterogeneity (I 2 = 77%, P < 0.01) were suggested.…”

“…A significant effect on symptoms (RR = 1.56; 95% CI 1.33-1.83) and significant heterogeneity were also detected (I 2 = 54%, P < 0.01). In the subgroup of probiotics type, there were 15 studies using single probiotics (Gade and Thorn, 1989;Nobaek et al, 2000;Niedzielin et al, 2001;Whorwell et al, 2006;Sinn et al, 2008;Enck et al, 2009;Guglielmetti et al, 2011;Dapoigny et al, 2012;Ducrotte et al, 2012;Kruis et al, 2012;Pineton de Chambrun et al, 2015;Mezzasalma et al, 2016;Spiller et al, 2016;Thijssen et al, 2016;Sun et al, 2018) and 21 studies using combination probiotics (Kim et al, 2003;Kajander et al, 2005;Kim et al, 2005;Guyonnet et al, 2007;Drouault-Holowacz et al, 2008;Enck et al, 2008;Hong et al, 2009;Simrén et al, 2010;Sondergaard et al, 2011;Cha et al, 2012;Cui and Hu, 2012;Begtrup et al, 2013;Roberts et al, 2013;Jafari et al, 2014;Lorenzo-Zuniga et al, 2014;Ludidi et al, 2014;Sisson et al, 2014;Yoon et al, 2014;Yoon et al, 2015;Mezzasalma et al, 2016;Hod et al, 2017). The RR of single and combination group was 1.76 (95% CI 1.37-2.25; Figure S3) and 1.39 (95% CI 1.18-1.65), respectively.…”