The Effectiveness of Synbiotic Preparation Containing Lactobacillus and Bifidobacterium Probiotic Strains and Short Chain Fructooligosaccharides in Patients with Diarrhea Predominant Irritable Bowel Syndrome-A Randomized Double-Blind, Placebo-Controlled Study

Barbara Skrzydło-Radomańska, Beata Prozorow-Król, Halina Cichoż-Lach, Emilia Majsiak, Joanna B Bierła, Wojciech Kosikowski, Mariusz Szczerbiński, Jesper Gantzel, Bożena Cukrowska, Barbara Skrzydło-Radomańska, Beata Prozorow-Król, Halina Cichoż-Lach, Emilia Majsiak, Joanna B Bierła, Wojciech Kosikowski, Mariusz Szczerbiński, Jesper Gantzel, Bożena Cukrowska

Abstract

The purpose of the randomized double-blind placebo-controlled trial was to assess the effectiveness of synbiotic preparation containing probiotic Lactobacillus rhamnosus FloraActive™ 19070-2, Lactobacillus acidophilus DSMZ 32418, Bifidobacterium lactis DSMZ 32269, Bifidobacterium longum DSMZ 32946, Bifidobacterium bifidum DSMZ 32403 and fructooligosaccharides in adult patients with diarrhea-dominant IBS (IBS-D). The study included eighty patients with moderate and severe IBS-D who were randomized to receive synbiotics or placebo for eight weeks. Finally, a total of sixty-eight patients finished the study. The primary endpoints included the assessment of the symptoms' severity with IBS symptom severity scale (IBS-SSS), an improvement of IBS global symptoms with Global Improvement Scale (IBS-GIS) and adequate relief of symptoms after four and eight weeks of therapy. Secondary endpoints, which were collected by telephone interviewers three times a week included the assessment of individual IBS symptoms and adverse events. Synbiotic treatment in comparison to placebo significantly improved IBS-GIS (p = 0.043), and IBS-SSS score inducing a decrease in the total IBS-SSS (p = 0.042) and in domain-specific scores related to flatulence (p = 0.028) and bowel habit (p = 0.028) after four and eight weeks. Patients treated with synbiotics reported in weekly observations a significant amelioration in a feeling of incomplete bowel movements, flatulence, pain, stool pressure and diarrheal stools compared to those receiving placebo. There were no differences in adverse events between both groups. Concluding, the multi-strain synbiotic preparation was associated with a significant improvement in symptoms in IBS-D patients and was well-tolerated. These results suggest that the use of synbiotics offers a benefit for IBS-D patients. [Clinicaltrials.gov NCT04206410 registered 20 December 2019].

Keywords: Bifidobacterium; Lactobacillus; irritable bowel syndrome; prebiotics; probiotics; short chain fructooligosaccharides; synbiotics.

Conflict of interest statement

B.C. has served as a speaker for Nutricia, Danone, Bayer, Apotex, Polpharma, and Mead Johnson. J.G. is the co-founder of Biocare Copenhagen, a company acquired by DSM Nutritional Products in 2017, but was not involved in conducting the study and data analyses. Other authors declare no conflict of interest.

Figures

Figure A1
Figure A1
The impact of the synbiotic treatment on (a) bowel movements, (b) the type of stool, (c) the severity of pain, (d) the severity of flatulence, (e) stool pressure, (f) incomplete bowel movements assessed by the telephone interviewers. All data were collected during telephone interviews 3 times per week for 8 weeks. Week 0—screening week before enrollment into the study. Results are presented as a mean ± SD of the number of bowel movements per day, 5-point (for the severity of pain, flatulence, stool pressure) or 2-point (for incomplete bowel movements) scores and Bristol scale stool for the type of stool. * statistically significant (p < 0.05) differences between the synbiotic and placebo groups.
Figure A1
Figure A1
The impact of the synbiotic treatment on (a) bowel movements, (b) the type of stool, (c) the severity of pain, (d) the severity of flatulence, (e) stool pressure, (f) incomplete bowel movements assessed by the telephone interviewers. All data were collected during telephone interviews 3 times per week for 8 weeks. Week 0—screening week before enrollment into the study. Results are presented as a mean ± SD of the number of bowel movements per day, 5-point (for the severity of pain, flatulence, stool pressure) or 2-point (for incomplete bowel movements) scores and Bristol scale stool for the type of stool. * statistically significant (p < 0.05) differences between the synbiotic and placebo groups.
Figure 1
Figure 1
The flowchart of study protocol.
Figure 2
Figure 2
The percentage of patients reported an improvement in dissatisfaction with bowel habits assessed by IBS-SSS scale after synbiotic intervention lasting 4 weeks (visit II) and 8-weeks (visit III). An improvement was defined as a 50-point decrease compared to baseline. N.S. = no significance (p > 0.05).
Figure 3
Figure 3
The impact of synbiotic treatment on the global improvement of IBS-symptoms (IBS-GIS) (a) and adequate relief (IBS-AR) (b). IBS-GIS and IBS-AR were evaluated after 4 weeks (visit II) and 8 weeks (visit III) of treatment. The results are presented as means of IBS-GIS score or the percentage of patients with adequate relief. A statistically significant improvement of IBS-GIS score between visits II and III was observed only in the synbiotic group, and a significantly amelioration in the synbiotic group compared with the placebo group was found after 8-week lasting treatment (visit III). No statistically significant differences were found in IBS-AR. N.S. = no significance (p > 0.05).
Figure 4
Figure 4
Weekly changes of IBS symptom scores of flatulence (a), abdominal pain (b), stool pressure (c), and a feeling of incomplete bowel movement (d) on a Likert scale (the lower the score the greater improvement). * Statistical significance between studied groups (p < 0.0001).
Figure 5
Figure 5
The impact of synbiotics on (a) the type of stool, (b) the severity of pain, (c) stool pressure, (d) the severity of flatulence, (e) incomplete bowel movements, (f) adverse events assessed by telephone interviewers. All data were collected during telephone interviews. Week 0—screening week before enrollment into the study (baseline). Results are presented as a percentage of patients who reported the severity of symptoms accordingly transformed into new scales described in Table 2. The table (g) presents p-values of a Fisher exact test and Cochran–Mantel–Haenszel test (CHM) and CHM statistic. 0 Synbiotic/0 Placebo—constipation, no or weak pain, flatulence and stool pressure, no feeling of incomplete bowel movements, no adverse events in the synbiotic/placebo group; 1 Synbiotic/1 Placebo—normal stool, intermediate pain, flatulence and stool pressure, presence of a feeling of incomplete bowel movements, presence of adverse events in the synbiotic/placebo group; 2 Synbiotic/2 Placebo—diarrhea, severe pain, flatulence and stool pressure in the synbiotic/placebo group.
Figure 5
Figure 5
The impact of synbiotics on (a) the type of stool, (b) the severity of pain, (c) stool pressure, (d) the severity of flatulence, (e) incomplete bowel movements, (f) adverse events assessed by telephone interviewers. All data were collected during telephone interviews. Week 0—screening week before enrollment into the study (baseline). Results are presented as a percentage of patients who reported the severity of symptoms accordingly transformed into new scales described in Table 2. The table (g) presents p-values of a Fisher exact test and Cochran–Mantel–Haenszel test (CHM) and CHM statistic. 0 Synbiotic/0 Placebo—constipation, no or weak pain, flatulence and stool pressure, no feeling of incomplete bowel movements, no adverse events in the synbiotic/placebo group; 1 Synbiotic/1 Placebo—normal stool, intermediate pain, flatulence and stool pressure, presence of a feeling of incomplete bowel movements, presence of adverse events in the synbiotic/placebo group; 2 Synbiotic/2 Placebo—diarrhea, severe pain, flatulence and stool pressure in the synbiotic/placebo group.

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